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Mattick J, Amaral P. RNA, the Epicenter of Genetic Information: A new understanding of molecular biology. Abingdon (UK): CRC Press; 2022 Sep 20.

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RNA, the Epicenter of Genetic Information: A new understanding of molecular biology.

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References

    Preface

    1.
    Weaver W. (1970) Molecular biology: Origin of the term. Science 170: 581–582. [PubMed: 4919180]

    Chapter 2

    1.
    Lavoisier A.L. (1789) Traité Élémentaire de Chimie (Chez Cuchet, New York).
    2.
    Proust J.L. (1794) Recherches sur le Bleu de Prusse. Journal de Physique, de Chimie, et d‘Histoire Naturelle 2: 334–341.
    3.
    Rocke A.J. (2005) In search of El Dorado: John Dalton and the origins of the atomic theory. Social Research 72: 125–158.
    4.
    Avogadro A. (1811) Essai d‘une manière de déterminer les masses relatives des molécules élémentaires des corps, et les proportions selon lesquelles elles entrent dans ces combinaisons. Journal de Physique, de Chimie et d’Histoire naturelle 73: 58–76.
    5.
    Hinshelwood C.N. and Pauling L. (1956) Amedeo Avogadro. Science 124: 708–713. [PubMed: 17757602]
    6.
    Marshall J.L. and Marshall V.R. Rediscovery of the elements: The periodic table. The Hexagon 98: 23–29.
    7.
    Nes W.D. (2011) Biosynthesis of cholesterol and other sterols. Chemical Reviews 111: 6423–6451. [PMC free article: PMC3191736] [PubMed: 21902244]
    8.
    Braconnot H. (1815) Sur la nature des corps gras. Annales de Chimie 2 (XCIII): 225–277.
    9.
    Chevreul M.E. (1823) Recherches Chimiques 1 (Wentworth Press, New York, 2018).
    10.
    Gobley T.N. (1847) Examen comparatif du jaune d‘oeuf et de la matière cérébrale. Journal de Pharmacie et de Chimie t11: 409–412.
    11.
    Bertrand G. Projet de reforme de la nomenclature de chimie biologique. Bulletin de la Société de Chimie Biologique 5: 96–109.
    12.
    Barnett J.A. (2003) Beginnings of microbiology and biochemistry: The contribution of yeast research. Microbiology 149: 557–567. [PubMed: 12634325]
    13.
    Payen A. and Persoz J.-F. (1833) Mémoire sur la diastase, les principaux produits de ses réactions et leurs applications aux arts industriels. Annales de Chimie et de Physique 53: 73–92.
    14.
    Dumas J.-B. (1839) Rapport sur un mémoire de M. Payen, relatif à la composition de la matière ligneuse Comptes Rendus 8: 51–53.
    15.
    Payen A. (1839) Mémoire sur les applications théoriques et pratiques des propriétés du tissu élémentaire des végétaux. Comptes Rendus 8: 59–61.
    16.
    Young F.G. (1957) Claude Bernard and the discovery of glycogen; a century of retrospect. British Medical Journal 1: 1431–1437. [PMC free article: PMC1973429] [PubMed: 13436813]
    17.
    Wöhler F. (1828) Ueber künstliche Bildung des Harnstoffs. Annalen der Physik und Chemie 88: 253–256.
    18.
    Toby S. (2000) Acid test finally wiped out vitalism, and yet. Nature 408: 767. [PubMed: 11130694]
    19.
    Mulder G.J. (1839) Ueber die Zusammensetzung einiger thierischen Substanzen. Journal für Praktische Chemie 16: 129–152.
    20.
    Teich M. and Needham D. (1992) A Documentary History of Biochemistry 1770–1940 (Leicester University Press, New York).
    21.
    Vickery H.B. (1950) The origin of the word protein. Yale Journal of Biology and Medicine 22: 387–393. [PMC free article: PMC2598953] [PubMed: 15413335]
    22.
    Hartley H. (1951) Origin of the word ‘protein’. Nature 168: 244. [PubMed: 14875059]
    23.
    Holmes F.L. (1979) Early theories of protein metabolism. Annals of the New York Academy of Sciences 325: 171–188. [PubMed: 378067]
    24.
    Rosenfeld L. (2003) Justus Liebig and animal chemistry. Clinical Chemistry 49: 1696–1707. [PubMed: 14500604]
    25.
    Glas E. (1999) The evolution of a scientific concept. Journal for General Philosophy of Science 30: 37–58.
    26.
    Welch G.R. and Clegg J.S. (2010) From protoplasmic theory to cellular systems biology: A 150-year reflection. American Journal of Physiology: Cell Physiology 298: C1280–90. [PubMed: 20200206]
    27.
    Huxley T.H. and Snell A.L.F. (1909) Autobiography and Selected Essays (Houghton Miflin Company, New York).
    28.
    Darwin F. (1887) The Life and Letters of Charles Darwin, Including an Autobiographical (John Murray, New York).
    29.
    Holmes D.S., Mayfield J.E. and Bonner J. (1974) Sequence composition of rat ascites chromosomal ribonucleic acid. Biochemistry 13: 849–855. [PubMed: 4360352]
    30.
    Globus N. and Blandford R.D. (2020) The chiral puzzle of life. The Astrophysical Journal 895: L11.
    31.
    Fischer E. (1894) EinfluD der Konfiguration auf die Wirkung der Enzyme. Berichte der Deutschen Chemischen Gesellschaft 27: 2985–2993.
    32.
    Kohler R. (1971) The background to Eduard Buchner’s discovery of cell-free fermentation. Journal of the History of Biology 4: 35–61. [PubMed: 11609437]
    33.
    Vickery H.B. and Schmidt C.L.A. (1931) The history of the discovery of the amino acids. Chemical Reviews 9: 169–318.
    34.
    Vickery H.B. and Osborne T.B. (1928) A review of hypotheses of the structure of proteins. Physiological Reviews 8: 393–446.
    35.
    Fruton J.S. (1985) Contrasts in scientific style. Emil Fischer and Franz Hofmeister: Their research groups and their theory of protein structure. Proceedings of the American Philosophical Society 129: 313–370. [PubMed: 11621201]
    36.
    Sumner J.B. (1926) The isolation and crystallization of the enzyme urease. Journal of Biological Chemistry 69: 435–441.
    37.
    Andras P. and Andras C. (2005) The origins of life – the ‘protein interaction world’ hypothesis: Protein interactions were the first form of self-reproducing life and nucleic acids evolved later as memory molecules. Medical Hypotheses 64: 678–688. [PubMed: 15694682]
    38.
    Oparin A.I. (1968) Genesis and Evolutionary Development of Life (Academic Press, New York).
    39.
    Lanham U.N. (1952) Oparin’s hypothesis and the evolution of nucleoproteins. American Naturalist 86: 213–218.
    40.
    Tirard S. (2017) J. B. S. Haldane and the origin of life. Journal of Genetics 96: 735–739. [PubMed: 29237880]
    41.
    Powner M.W., Gerland B. and Sutherland J.D. (2009) Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459: 239–242. [PubMed: 19444213]
    42.
    Patel B.H., Percivalle C., Ritson D.J., Duffy C.D. and Sutherland J.D. (2015) Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism. Nature Chemistry 7: 301–307. [PMC free article: PMC4568310] [PubMed: 25803468]
    43.
    Ferus M., et al. (2017) Formation of nucleobases in a Miller–Urey reducing atmosphere. Proceedings of the National Academy of Sciences USA 114: 4306–4311. [PMC free article: PMC5410828] [PubMed: 28396441]
    44.
    Becker S., et al. (2019) Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides. Science 366: 76–82. [PubMed: 31604305]
    45.
    Miller S.L. (1953) A production of amino acids under possible primitive earth conditions. Science 117: 528–529. [PubMed: 13056598]
    46.
    Miller S.L. and Urey H.C. (1959) Organic compound synthesis on the primitive Earth. Science 130: 245–251. [PubMed: 13668555]
    47.
    Weaver W. (1970) Molecular biology: Origin of the term. Science 170: 581–582. [PubMed: 4919180]
    48.
    Turing A.M. (1952) The chemical basis of morphogenesis. Philosophical Transactions of the Royal Society B: Biological Sciences 237: 37–72. [PMC free article: PMC4360114] [PubMed: 25750229]
    49.
    Kornberg H. (2000) Krebs and his trinity of cycles. Nature Reviews Molecular Cell Biology 1: 225–228. [PubMed: 11252898]
    50.
    Wakil S.J. (1962) Lipid metabolism. Annual Review of Biochemistry 31: 369–406. [PubMed: 14004468]
    51.
    Bender D.A. (2012) Amino Acid Metabolism, 3rd edition (John Wiley & Sons, New York).
    52.
    Nelson D.A. and Cox M. (2016) Lehninger Principles of Biochemistry, 7th edition: International Edition (Macmillan, New York).
    53.
    Yasuo T., Kusuhara Y., Yasumatsu K. and Ninomiya Y. (2008) Multiple receptor systems for glutamate detection in the taste organ. Biological & Pharmaceutical Bulletin 31: 1833–1837. [PubMed: 18827337]
    54.
    Olby R. (1994) The Path to the Double Helix: The Discovery of DNA (Dover Publications, New York).
    55.
    Hunter G.K. (2000) Vital Forces: The Discovery of the Molecular Basis of Life (Academic Press, New York).
    56.
    Dahm R. (2008) Discovering DNA: Friedrich Miescher and the early years of nucleic acid research. Human Genetics 122: 565–581. [PubMed: 17901982]
    57.
    Dahm R. (2010) From discovering to understanding. Friedrich Miescher’s attempts to uncover the function of DNA. EMBO Reports 11: 153–160. [PMC free article: PMC2838690] [PubMed: 20168329]
    58.
    Veigl S.J., Harman O. and Lamm E. (2020) Friedrich Miescher’s discovery in the historiography of Genetics: From contamination to confusion, from nuclein to DNA. Journal of the History of Biology 53: 451–484. [PubMed: 32524311]
    59.
    Lamm E., Harman O. and Veigl S.J. (2020) Before Watson and Crick in 1953 came Friedrich Miescher in 1869. Genetics 215: 291–296. [PMC free article: PMC7268995] [PubMed: 32487691]
    60.
    Flemming W. (1878) Zur Kenntniss der Zelle und ihrer Theilungs-Erscheinungen. Schriften des Naturwissenschaftlichen Vereins für Schleswig-Holstein 3: 23–27.
    61.
    Flemming W. (1882) Zellsubstanz, Kern und Zelltheilung (Cell substance, nucleus and cell division) (F. C. W. Vogel, New York).
    62.
    Paweletz N. (2001) Walther flemming: Pioneer of mitosis research. Nature Reviews Molecular Cell Biology 2: 72–75. [PubMed: 11413469]
    63.
    Flemming W. (1875) Studien uber die Entwicklungsgeschichte der Najaden. Sitzungsberichte der Kaiserlichen Akademie der Wissenschaften Wien 71: 81–147.
    64.
    Van Beneden E. (1876) Contribution a l’histoire de la vesiculaire germinative et du premier noyau embryonnaire. Bulletins de l‘Académie royale des sciences, des lettres et des beaux-arts de Belgique (2me série) 42: 35–97.
    65.
    Boveri T. (1888) Zellen-Studien II. Die Befruchtung und Teilung des Eies von Ascaris megalocephala. Jenaische Zeitschrift für Naturwissenschaft 22: 685–882.
    66.
    Boveri T. (1901) Zellen-studien IV: Über die Natur der Centrosomen. Jenaische Zeitschrift für Naturwissenschaft 35: 1–220.
    67.
    Waldeyer W. (1888) Ueber Karyokinese und ihre Beziehungen zu den Befruchtungsvorgängen. Archiv für mikroskopische Anatomie 32: 1.
    68.
    Kossel A. (1967) The chemical composition of the cell nucleus, in Nobel Lectures Physiology or Medicine 1901–1921 (Elsevier Publishing Company, New York). https://www​.nobelprize​.org/prizes/medicine​/1910/kossel/lecture/
    69.
    Jones M.E. (1953) Albrecht Kossel, a biographical sketch. Yale Journal of Biology and Medicine 26: 80–97. [PMC free article: PMC2599350] [PubMed: 13103145]
    70.
    Roberts H.F. (1929) Plant Hybridization before Mendel (Princeton University Press, New York).
    71.
    Simunek M., Hoßfeld U., Thümmler F. and Breidbach O. (2011) The Mendelian Dioskuri: Correspondence of Armin with Erich von Tschermak-Seysenegg, 1898–1951 (Institute of Contemporary History of the Academy of Sciences Prague & Pavel Mervart, Červený Kostelec, Czech Republic). https:​//www-pavelmervart-cz​.translate.goog​/kontakt/?_x_tr_sl​=cs&_x_tr_tl​=en&_x_tr_hl​=en&_x_tr_pto​=sc&_x_tr_sch=http
    72.
    Simunek M., Hoßfeld U., Thümmler F. and Sekerák J. (2011) The Letters on G. J. Mendel – Correspondence of William Bateson, Hugo Iltis, and Erich von Tschermak-Seysenegg with Alois and Ferdinand Schindler, 1902–1935 (Institute of Contemporary History of the Academy of Sciences Prague & Pavel Mervart).
    73.
    Friedrich-Schiller-Universitaet Jena (2011) Early history of genetics revised: New light shed on ‘rediscovery’ of Mendel’s laws of heredity. ScienceDaily 3 May 2011.
    74.
    Mendel G. (1865) Versuche über Plflanzen-hybriden (Experiments in Plant Hybridization, Bateson Translation). Verhandlungen des naturforschenden Vereines in Brünn IV: 3–47.
    75.
    Bateson W. (1909) Mendel’s Principles of Heredity (Cambridge University Press, New York).
    76.
    Satzinger H. (2008) Theodor and Marcella Boveri: Chromosomes and cytoplasm in heredity and development. Nature Reviews Genetics 9: 231–238. [PubMed: 18268510]
    77.
    Rabi C. (1885) On cell division. Morphological Yearbook 10: 214–330.
    78.
    Boveri T. (1909) Die Blastomerenkerne von Ascaris megalocephala und die Theorie der Chromosomenindividualität. Archiv für Zellforschung 3: 181–268.
    79.
    Hansford S. and Huntsman D.G. (2014) Boveri at 100: Theodor Boveri and genetic predisposition to cancer. Journal of Pathology 234: 142–145. [PubMed: 25074498]
    80.
    Sutton W.S. (1903) The chromosomes in heredity. Biological Bulletin 4: 231–251.
    81.
    Halliburton W.D. (1895) Nucleo-proteids. Journal of Physiology 18: 306–318. [PMC free article: PMC1514591] [PubMed: 16992257]
    82.
    Johannsen W. (1909) Elemente der exakten Erblichkeitslehre (Gustav Fischer, New York).
    83.
    Johannsen W. (1911) The genotype conception of heredity. American Naturalist 45: 129–159.
    84.
    Brush S.G. (1978) Nettie M. Stevens and the discovery of sex determination by chromosomes. Isis 69: 163–172. [PubMed: 389882]
    85.
    Wilson E.B. (1905) The chromosomes in relation to the determination of sex in insects. Science 22: 500–502. [PubMed: 17748139]
    86.
    Bridges C.B. (1914) Direct proof through non-disjunction that the sex-linked genes of Drosophila are borne by the X-chromosome. Science 40: 107–109. [PubMed: 17807969]
    87.
    Bridges C.B. (1916) Non-disjunction as proof of the chromosome theory of heredity. Genetics 1: 1–52. [PMC free article: PMC1193653] [PubMed: 17245850]
    88.
    Rubin G.M. and Lewis E.B. (2000) A brief history of Drosophila’s contributions to genome research. Science 287: 2216–2218. [PubMed: 10731135]
    89.
    Sturtevant A.H. (1913) The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association. Journal of Experimental Zoology 14: 43–59.
    90.
    Morgan T.H., Bridges C.B., Muller H.J. and Sturtevant A.H. (1915) The Mechanism of Mendelian Heredity (Henry Holt and Company, New York).
    91.
    Morgan T.H. (1922) C.roonian lecture:—On the mechanism of heredity. Proceedings of the Royal Society B: Biological Sciences 94: 162–197.
    92.
    Muller H.J. (1930) Types of visible variations induced by X-rays in Drosophila. Journal of Genetics 22: 299–334.
    93.
    Edwards A.W.F. (2012) Reginald Crundall Punnett: First Arthur Balfour Professor of Genetics, Cambridge, 1912. Genetics 192: 3–13. [PMC free article: PMC3430543] [PubMed: 22964834]
    94.
    Strauss B.S. (2016) Biochemical genetics and molecular biology: The contributions of George Beadle and Edward Tatum. Genetics 203: 13–20. [PMC free article: PMC4858768] [PubMed: 27183563]
    95.
    Strauss B.S. (2017) A physicist’s quest in biology: Max Delbrück and “Complementarity”. Genetics 206: 641–650. [PMC free article: PMC5499177] [PubMed: 28592501]
    96.
    Timoféeff-Ressovsky N.W. (1927) Studies on the phenotypic manifestation of hereditary factors. I. On the phenotypic manifestation of the genovariation radius incompletus in Drosophila funebris. Genetics 12: 128–198. [PMC free article: PMC1200936] [PubMed: 17246520]
    97.
    Timoféeff-Ressovsky N.V., Zimmer K.G. and Delbrück M. (1935) Ueber die Natur der Genmutation und der Genstruktur. Nachrichten von der Gesellschaft der Wissenschaften zu Göttingen, Mathematisch-Physikalische Klasse, Fachgruppe VI 1: 189–245.
    98.
    Ratner V.A. (2001) Nikolay Vladimirovich Timoféeff-Ressovsky (1900–1981): Twin of the century of genetics. Genetics 158: 933–939. [PMC free article: PMC1461703] [PubMed: 11454744]
    99.
    Elgin S.C.R. and Reuter G. (2013) Position-effect variegation, heterochromatin formation, and gene silencing in Drosophila. Cold Spring Harbor Perspectives in Biology 5: a017780. [PMC free article: PMC3721279] [PubMed: 23906716]
    100.
    Muller H.J., Prokofyeva A. and Raffel D. (1935) Minute intergenic rearrangement as a cause of apparent gene mutation. Nature 135: 253–255.
    101.
    Goldschmidt R. (1937) Spontaneous chromatin rearrangements in Drosophila. Nature 140: 767. [PMC free article: PMC1077008] [PubMed: 16577830]
    102.
    Dietrich M.R. (2003) Richard goldschmidt: Hopeful monsters and other ‘heresies’. Nature Reviews Genetics 4: 68–74. [PubMed: 12509755]
    103.
    Barrell B.G., Air G.M. and Hutchison 3rd, C.A. (1976) Overlapping genes in bacteriophage phiX174. Nature 264: 34–41. [PubMed: 1004533]
    104.
    Henikoff S., Keene M.A., Fechtel K. and Fristrom J.W. (1986) Gene within a gene: Nested Drosophila genes encode unrelated proteins on opposite DNA strands. Cell 44: 33–42. [PubMed: 3079672]
    105.
    Gott J.M. et al. (1988) Genes within genes: Independent expression of phage T4 intron open reading frames and the genes in which they reside. Genes & Development 2: 1791–1799. [PubMed: 2467840]
    106.
    Kapranov P. et al. (2005) Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. Genome Research 15: 987–997. [PMC free article: PMC1172043] [PubMed: 15998911]
    107.
    Carninci P. et al. (2005) The transcriptional landscape of the mammalian genome. Science 309: 1559–1563. [PubMed: 16141072]
    108.
    Denoeud F. et al. (2007) Prominent use of distal 5′ transcription start sites and discovery of a large number of additional exons in ENCODE regions. Genome Research 17: 746–759. [PMC free article: PMC1891335] [PubMed: 17567994]
    109.
    Kapranov P., et al. (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316: 1484–1488. [PubMed: 17510325]
    110.
    Kumar A. (2009) An overview of nested genes in eukaryotic genomes. Eukaryotic Cell 8: 1321–1329. [PMC free article: PMC2747821] [PubMed: 19542305]
    111.
    Goldschmidt R. (1935) Gen und Außeneigenschaft (Untersuchungen anDrosophila) I. Zeitschrift für induktive Abstammungs- und Vererbungslehre 69: 38–69.
    112.
    Lamm E. (2008) Hopeful heretic–Richard Goldschmidt’s genetic metaphors. History and Philosophy of the Life Sciences 30: 387–405. [PubMed: 19579710]
    113.
    Ayala F.J. and Fitch W.M. (1997) Genetics and the origin of species: An introduction. Proceedings of the National Academy of Sciences USA 94: 7691–7697. [PMC free article: PMC33678] [PubMed: 9223250]
    114.
    Dobzhansky T. (1973) Nothing in biology makes sense except in the light of evolution. The American Biology Teacher 35: 125–129.
    115.
    Huxley J. (1942) Evolution: The Modern Synthesis (George Allen & Unwin Ltd., New York).
    116.
    Provine W.B. (1971) The Origins of Theoretical Population Genetics (University of Chicago Press, New York).
    117.
    Visscher P.M. and Goddard M.E. (2019) From R.A. Fisher’s 1918 paper to GWAS a century later. Genetics 211: 1125–1130. [PMC free article: PMC6456325] [PubMed: 30967441]
    118.
    Darlington C.D. and Ford E.B. (1956) Natural populations and the breakdown of classical genetics. Proceedings of the Royal Society B: Biological Sciences 145: 350–364. [PubMed: 13359390]
    119.
    Harman O.S. (2005) Cyril Dean Darlington: The man who ‘invented’ the chromosome. Nature Reviews Genetics 6: 79–85. [PubMed: 15630424]
    120.
    Haldane J.B.S. (1924) A mathematical theory of natural and artificial selection. Part II the influence of partial self-fertilisation, inbreeding, assortative mating, and selective fertilisation on the composition of mendelian populations, and on natural selection. Biological Reviews 1: 158–163.
    121.
    v’ant Hof A.E., et al. (2016) The industrial melanism mutation in British peppered moths is a transposable element. Nature 534: 102–105. [PubMed: 27251284]
    122.
    Fisher R.A. (1918) The correlation between relatives on the supposition of Mendelian inheritance. Transactions of the Royal Society of Edinburgh 53: 399–433.
    123.
    Fisher R.A. (1930) The Genetical Theory of Natural Selection (Clarendon Press, New York).
    124.
    Edwards A.W. (2000) The genetical theory of natural selection. Genetics 154: 1419–1426. [PMC free article: PMC1461012] [PubMed: 10747041]
    125.
    Darwin C. (1859) On the Origin of Species by Means of Natural Selection (John Murray, New York).
    126.
    Fitzgerald D.M. and Rosenberg S.M. (2019) What is mutation? A chapter in the series: How microbes “jeopardize” the modern synthesis. PLOS Genetics 15: e1007995. [PMC free article: PMC6443146] [PubMed: 30933985]
    127.
    Weismann A. (1889) Essays Upon Heredity and Kindred Biological Problems. Authorized translation (Clarendon Press, New York).
    128.
    Nilsson E.E., Maamar M.B. and Skinner M.K. (2020) Environmentally induced epigenetic transgenerational inheritance and the Weismann Barrier: The dawn of Neo-Lamarckian theory. Journal of Developmental Biology 8: 28. [PMC free article: PMC7768451] [PubMed: 33291540]
    129.
    Waddington C.H. (1942) Canalization of development and the inheritance of acquired characters. Nature 150: 563–565.
    130.
    Waddington C.H. (1953) Genetic assimilation of an acquired character. Evolution 7: 118–126.
    131.
    Waddington C.H. (1956) Genetic assimilation of the bithorax phenotype. Evolution 10: 1–13.
    132.
    Cairns J. (2008) The foundations of molecular biology: A 50th anniversary. Current Biology 18: R234–6. [PubMed: 18364220]
    133.
    Delbruck M. (1940) Radiation and the hereditary mechanism. The American Naturalist 74: 350–362.
    134.
    Lederberg J. and Lederberg E.M. (1952) Replica plating and indirect selection of bacterial mutants. Journal of Bacteriology 63: 399–406. [PMC free article: PMC169282] [PubMed: 14927572]
    135.
    Galton F. (1875) The history of twins, as a criterion of the relative powers of nature and nurture. Fraser’s Magazine 12: 566–576. [PubMed: 22933639]
    136.
    Durant J.R. (1979) Scientific naturalism and social reform in the thought of Alfred Russel Wallace. British Journal for the History of Science 12: 31–58.
    137.
    Provine W.B. and Russell E.S. (1986) Geneticists and race. American Zoologist 26: 857–887.
    138.
    Caspari E.W. and Marshak R.E. (1965) The rise and fall of Lysenko. Science 149: 275–278. [PubMed: 17838094]
    139.
    Soyfer V.N. (2001) The consequences of political dictatorship for Russian science. Nature Reviews Genetics 2: 723–729. [PubMed: 11533721]
    140.
    Reichard P. (2002) Oswald T. Avery and the Nobel Prize in medicine. Journal of Biological Chemistry 277: 13355–13362. [PubMed: 11872756]
    141.
    Levene P.A. (1909) Uber die Hefenucleinsaure. Biochemische Zeitschrift 17: 120–131.
    142.
    Levene P.A. (1919) The structure of yeast nucleic acid. Journal of Biological Chemistry 40: 415–424.
    143.
    Levene P.A. and Jacobs W.A. (1912) On the structure of thymus nucleic acid. Journal of Biological Chemistry 12: 411–420.
    144.
    Stent G.S. (1970) DNA. Daedalus 99: 909–937. [PubMed: 11609640]
    145.
    Hargittai I. (2009) The tetranucleotide hypothesis: A centennial. Structural Chemistry 20: 753–756.
    146.
    Levene P.A. and Jacobs W.A. (1909) Über die Hefe-Nucleinsäure. Berichte der deutschen chemischen Gesellschaft 42: 2474–2478.
    147.
    Frixione E. and Ruiz-Zamarripa L. (2019) The “scientific catastrophe” in nucleic acids research that boosted molecular biology. Journal of Biological Chemistry 294: 2249–2255. [PMC free article: PMC6378961] [PubMed: 30765511]
    148.
    Signer R., Caspersson T. and Hammarsten E. (1938) Molecular shape and size of thymonucleic acid. Nature 141: 122.
    149.
    Kerr S.E., Seraidarian K. and Wargon M. (1949) Studies on ribonucleic acid: III. On the composition of the ribonucleic acid of beef pancreas, with notes on the action of ribonuclease. Journal of Biological Chemistry 181: 773–780. [PubMed: 15393796]
    150.
    Levene P.A. and Bass L.W. (1931) Nucleic Acids (Chemical Catalog Company, New York).
    151.
    Davidson J.N. and Waymouth C. (1943) Ribonucleic acids in animal tissues. Nature 152: 47–48.
    152.
    Allen F.W. (1941) The biochemistry of the nucleic acids, purines, and pyrimidines. Annual Review of Biochemistry 10: 221–244.
    153.
    Chargaff E. (1950) Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia 6: 201–209. [PubMed: 15421335]
    154.
    Feulgen R. and Rossenbeck H. (1924) Mikroskopisch-chemischer Nachweis einer Nucleinsäure von Typus der Thymonucleinsäure und die darauf beruhende elektive Färbung von Zellkernen in Mikroskopischer Praäparaten. Zeitschrift für physiologische Chemie 135: 203–248.
    155.
    Kasten F.H. (2003) Robert Feulgen and his histochemical reaction for DNA. Biotechnic & Histochemistry 78: 45–49. [PubMed: 12713141]
    156.
    Brachet J. (1933) Recherches sur la synthese de l‘acide thymonucleique pendant le developpement de l’oeuf d‘oursin. Archives de Biologie 44: 519–576.
    157.
    Brachet J. (1941) La localisation des acides pentosenucléiques dans les tissus animaux et les oeufs d‘amphibiens en voie de développement. Archives de Biologie 53: 207–257.
    158.
    Brachet J. (1941) La detection histochimique et la microdosage des acides pentosenucléiques. Enzymologia 10: 87–96.
    159.
    Brachet J. (1950) The localization and the role of ribonucleic acid in the cell. Annals of the New York Academy of Sciences 50: 861–869.
    160.
    Brachet J.L.A. (1960) The Biological Role of Ribonucleic Acids. Sixth Weizmann Memorial Lecture Series (Elsevier, New York).
    161.
    Belozersky A.N. and Spirin A.S. (1958) Correlation between the compositions of deoxyribonucleic and ribonucleic acids. Nature 182: 111–112. [PubMed: 13566202]
    162.
    Sevag M.G., Smolens J. and Lackman D.B. (1940) The nucleic acid content and distribution in Streptococcus pyogenes. Journal of Biological Chemistry 134: 523–529.
    163.
    Westhof E. and Fritsch V. (2000) RNA folding: Beyond Watson–crick pairs. Structure 8: R55–65. [PubMed: 10745012]
    164.
    Leontis N.B., Lescoute A. and Westhof E. (2006) The building blocks and motifs of RNA architecture. Current Opinion in Structural Biology 16: 279–287. [PMC free article: PMC4857889] [PubMed: 16713707]
    165.
    Brown D.M. and Todd A.R. (1955) Nucleic acids. Annual Review of Biochemistry 24: 311–338. [PubMed: 13249358]
    166.
    Todd A. (1958) Synthesis in the study of nucleotides; basic work on phosphorylation opens the way to an attack on nucleic acids and nucleotide coenzymes. Science 127: 787–792. [PubMed: 13543331]
    167.
    Bawden F.C. and Pirie N.W. (1937) The isolation and some properties of liquid crystalline substances from solanaceous plants infected with three strains of tobacco mosaic virus. Proceedings of the Royal Society B: Biological Sciences 123: 274–320.
    168.
    Stanley W.M. (1935) Isolation of a crystalline protein possessing the properties of tobacco-mosaic virus. Science 81: 644–645. [PubMed: 17743301]
    169.
    Gierer A. and Schramm G. (1956) Infectivity of ribonucleic acid from tobacco mosaic virus. Nature 177: 702–703. [PubMed: 13321939]
    170.
    Markham R. (1953) Virus nucleic acids. Advances in Virus Research 1: 315–332. [PubMed: 13104199]
    171.
    Garrod A.E. (1902) The incidence of alkaptonuria a study in chemical individuality. Lancet 2: 1616–1620. [PMC free article: PMC2230159] [PubMed: 8784780]
    172.
    Garrod A. (1908) On inborn errors of metabolism. The croonian lectures. Lancet 172: 1–7.
    173.
    Lederberg J. and McCray A.T. (2001) ‘Ome Sweet ’Omics—a genealogical treasury of words. The Scientist 15: 8.
    174.
    Beadle G.W. and Tatum E.L. (1941) Genetic control of biochemical reactions in Neurospora. Proceedings of the National Academy of Sciences USA 27: 499–506. [PMC free article: PMC1078370] [PubMed: 16588492]
    175.
    Wright S. (1917) Color inheritance in mammals: II. The mouse—better adapted to experimental work than any other mammal—seven sets of mendelian allelomorphs identified—factorial hypothesis framed by Cuenot on basis of his work with mice. Journal of Heredity 8: 373–378.
    176.
    Goldschmidt R. (1951) L. Cuénot: 1866–1951. Science 113: 309–310. [PubMed: 14817281]
    177.
    Buican D. (1982) Mendelism in France and the work of Lucien Cuénot. Scientia 76: 129–137.
    178.
    Hickman M. and Cairns J. (2003) The centenary of the one-gene one-enzyme hypothesis. Genetics 163: 839–841. [PMC free article: PMC1462495] [PubMed: 12663526]
    179.
    Morgan H.D., Sutherland H.G.E., Martin D.I.K. and Whitelaw E. (1999) Epigenetic inheritance at the agouti locus in the mouse. Nature Genetics 23: 314–318. [PubMed: 10545949]
    180.
    Whitelaw E. and Martin D.I. (2001) Retrotransposons as epigenetic mediators of phenotypic variation in mammals. Nature Genetics 27: 361–365. [PubMed: 11279513]
    181.
    Horowitz N.H. (1991) Fifty years ago: The Neurospora revolution. Genetics 127: 631–635. [PMC free article: PMC1204391] [PubMed: 1827628]
    182.
    Davis R.H. and Perkins D.D. (2002) Neurospora: A model of model microbes. Nature Reviews Genetics 3: 397–403. [PubMed: 11988765]
    183.
    Whitaker R.J. and Barton H.A. (2018) Women in Microbiology (American Society of Microbiology, New York).
    184.
    Lederberg J. and Tatum E.L. (1946) Gene recombination in Escherichia coli. Nature 158: 558. [PubMed: 21001945]
    185.
    Caspersson T. and Schultz J. (1938) Nucleic acid metabolism of the chromosomes in relation to gene reproduction. Nature 142: 294–295.
    186.
    Twort F.W. (1915) An investigation on the nature of ultra-microscopic viruses. Lancet 186: 1241–1243. [PMC free article: PMC2170983] [PubMed: 20475326]
    187.
    Schrödinger E. (1944) What Is Life? The Physical Aspect of the Living Cell (Cambridge Univ. Press, New York).
    188.
    Cobb M. (2016) Life’s Greatest Secret: The Race to Crack the Genetic Code (Profile Books, New York).
    189.
    Griffith F. (1928) The significance of Pneumococcal types. Journal of Hygiene 27: 113–159. [PMC free article: PMC2167760] [PubMed: 20474956]
    190.
    Avery O.T., MacLeod C.M. and McCarty M. (1944) Studies on the chemical nature of the substance inducing transformation of Pneumococcal types: Induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus type III. Journal of Experimental Medicine 79: 137–158. [PMC free article: PMC2135445] [PubMed: 19871359]
    191.
    Boivin A., Vendrely R. and Lehoult Y. (1945) L’acide thymonucléique hautement polymerisé, principe capable de conditionner la specificité sérologique et l’équipement enzymatique des Bactéries. Conséquences pour la biochimie de l’hérédité. Comptes Rendus de l‘Académie des Sciences 221: 646–648. [PubMed: 20989359]
    192.
    Stent G.S. (1972) Prematurity and uniqueness in scientific discovery. Scientific American 227: 84–93. [PubMed: 4564019]
    193.
    Cobb M. (2014) Oswald Avery, DNA, and the transformation of biology. Current Biology 24: R55–60. [PubMed: 24456972]
    194.
    Various (1983) Nature conference: Thirty years of DNA. Nature 302: 651–654. [PubMed: 6835401]
    195.
    Hershey A.D. and Chase M. (1952) Independent functions of viral protein and nucleic acid in growth of bacteriophage. Journal of General Physiology 36: 39–56. [PMC free article: PMC2147348] [PubMed: 12981234]
    196.
    Johnson T.B. and Coghill R.D. (1925) Researches on pyrimidines. C111. The discovery of 5-methyl-cytosine in tuberculinic acid, the nucleic acid of the tubercle bacillus. Journal of the American Chemical Society 47: 2838–2844.
    197.
    Hotchkiss R.D. (1948) The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. Journal of Biological Chemistry 175: 315–332. [PubMed: 18873306]
    198.
    Wyatt G.R. (1950) Occurrence of 5-methylcytosine in nucleic acids. Nature 166: 237–238. [PubMed: 15439258]
    199.
    Rudner R., Karkas J.D. and Chargaff E. (1968) Separation of B. subtilis DNA into complementary strands. 3. Direct analysis. Proceedings of the National Academy of Sciences USA 60: 921–922. [PMC free article: PMC225140] [PubMed: 4970114]
    200.
    Rogerson A.C. (1991) There appear to be conserved constraints on the distribution of nucleotide sequences in cellular genomes. Journal of Molecular Evolution 32: 24–30. [PubMed: 1901365]
    201.
    Fickett J.W., Torney D.C. and Wolf D.R. (1992) Base compositional structure of genomes. Genomics 13: 1056–1064. [PubMed: 1505943]
    202.
    Prabhu V.V. (1993) Symmetry observations in long nucleotide sequences. Nucleic Acids Research 21: 2797–2800. [PMC free article: PMC309655] [PubMed: 8332488]
    203.
    Qi D. and Cuticchia A.J. (2001) Compositional symmetries in complete genomes. Bioinformatics 17: 557–559. [PubMed: 11395434]
    204.
    Albrecht-Buehler G. (2006) Asymptotically increasing compliance of genomes with Chargaff’s second parity rules through inversions and inverted transpositions. Proceedings of the National Academy of Sciences USA 103: 17828–17833. [PMC free article: PMC1635160] [PubMed: 17093051]
    205.
    Shporer S., Chor B., Rosset S. and Horn D. (2016) Inversion symmetry of DNA k-mer counts: Validity and deviations. BMC Genomics 17: 696. [PMC free article: PMC5006273] [PubMed: 27580854]
    206.
    Cristadoro G., Degli Esposti M. and Altmann E.G. (2018) The common origin of symmetry and structure in genetic sequences. Scientific Reports 8: 15817. [PMC free article: PMC6202410] [PubMed: 30361485]
    207.
    Vischer E. and Chargaff E. (1948) The composition of the pentose nucleic acids of yeast and pancreas. Journal of Biological Chemistry 176: 715–734. [PubMed: 18889927]
    208.
    Chargaff E., Vischer E., Doniger R., Green C. and Misani F. (1949) The composition of the desoxypentose nucleic acids of thymus and spleen. Journal of Biological Chemistry 177: 405–416. [PubMed: 18107444]
    209.
    Vischer E., Zamenhof S. and Chargaff E. (1949) Microbial nucleic acids: The desoxypentose nucleic acids of avian tubercle bacilli and yeast. Journal of Biological Chemistry 177: 429–438. [PubMed: 18107446]
    210.
    Maddox B. (2002) Rosalind Franklin: The Dark Lady of DNA (HarperCollins, New York).
    211.
    Williams G. (2019) Unravelling the Double Helix: The Lost Heroes of DNA (Weidenfeld & Nicolson, New York).
    212.
    Astbury W.T. and Bell F.O. (1938) X-ray study of thymonucleic acid. Nature 141: 747–748.
    213.
    Astbury W.T. (1947) X-ray studies of nucleic acids. Symposia of the Society for Experimental Biology 1: 66–76. [PubMed: 20257017]
    214.
    Watson J.D. and Crick F.H. (1953) Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171: 737–738. [PubMed: 13054692]
    215.
    Franklin R.E. and Gosling R.G. (1953) Molecular configuration in sodium thymonucleate. Nature 171: 740–741. [PubMed: 13054694]
    216.
    Fuller W. (2003) Who said ‘helix’? Nature 424: 876–878. [PubMed: 12931159]
    217.
    Cobb M. (2017) 60 years ago, Francis Crick changed the logic of biology. PLOS Biology 15: e2003243. [PMC free article: PMC5602739] [PubMed: 28922352]
    218.
    Olby R. (2003) Quiet debut for the double helix. Nature 421: 402–405. [PubMed: 12540907]
    219.
    Meselson M. and Stahl F.W. (1958) The replication of DNA in Escherichia coli. Proceedings of the National Academy of Sciences USA 44: 671–682. [PMC free article: PMC528642] [PubMed: 16590258]
    220.
    Bessman M.J., Kornberg A., Lehman I.R. and Simms E.S. (1956) Enzymic synthesis of deoxyribonucleic acid. Biochimica et Biophysica Acta 21: 197–198. [PubMed: 13363894]
    221.
    Kornberg A., Kornberg S.R. and Simms E.S. (1956) Metaphosphate synthesis by an enzyme from Escherichia coli. Biochimica et Biophysica Acta 20: 215–227. [PubMed: 13315368]
    222.
    Lehman I.R. (2003) Discovery of DNA polymerase. Journal of Biological Chemistry 278: 34733–34738. [PubMed: 12791679]
    223.
    Peacocke A. (2005) Historical article: Titration studies and the structure of DNA. Trends in Biochemical Sciences 30: 160–162. [PubMed: 15752988]
    224.
    Creeth J.M. (1948) Some Physico-chemical Studies on Nucleic Acids and Related Substances. Ph.D. Dissertation, University of London. http://ethos​.bl.uk/OrderDetails​.do?did=1&uin=uk​.bl.ethos.729338.
    225.
    Harding S.E., Channell G. and Phillips-Jones M.K. (2018) The discovery of hydrogen bonds in DNA and a re-evaluation of the 1948 Creeth two-chain model for its structure. Biochemical Society Transactions 46: 1171–1182. [PMC free article: PMC6195643] [PubMed: 30190332]
    226.
    Shing Ho P. and Carter M. (2011) DNA structure: Alphabet soup for the cellular soul, in DNA Replication - Current Advances (InTechOpen).
    227.
    Rich A. (2009) The era of RNA awakening: Structural biology of RNA in the early years. Quarterly Reviews of Biophysics 42: 117–137. [PubMed: 19638248]
    228.
    Nikolova E.N. et al. (2013) A historical account of Hoogsteen base-pairs in duplex DNA. Biopolymers 99: 955–968. [PMC free article: PMC3844552] [PubMed: 23818176]
    229.
    Herbert A. and Rich A. (1999) Left-handed Z-DNA: Structure and function. Genetica 106: 37–47. [PubMed: 10710708]
    230.
    Spiegel J., Adhikari S. and Balasubramanian S. (2020) The structure and function of DNA G-quadruplexes. Trends in Chemistry 2: 123–136. [PMC free article: PMC7472594] [PubMed: 32923997]
    231.
    Zeraati M. et al. (2018) I-motif DNA structures are formed in the nuclei of human cells. Nature Chemistry 10: 631–637. [PubMed: 29686376]
    232.
    Calladine C.R., Drew H.R., Luisi B.F. and Travers A.A. (2004) Understanding DNA. 3rd edition. The Molecule and How it Works (Academic Press, New York).
    233.
    Doty P., Marmur J., Eigner J. and Schildkraut C. (1960) Strand separation and specific recombination in deoxyribonucleic acids: Physical chemical studies. Proceedings of the National Academy of Sciences USA 46: 461–476. [PMC free article: PMC222859] [PubMed: 16590628]
    234.
    Marmur J. and Doty P. (1961) Thermal renaturation of deoxyribonucleic acids. Journal of Molecular Biology 3: 585–594. [PubMed: 14470100]

    Chapter 3

    1.
    Brachet J. and Chantrenne H. (1951) Protein synthesis in nucleated and non-nucleated halves of Acetabularia mediterranea studied with carbon-14 dioxide. Nature 168: 950. [PubMed: 14910602]
    2.
    Hammerling J. (1953) Nucleo-cytoplasmic relationships in the development of Acetabularia. International Review of Cytology 2: 475–498.
    3.
    Caspersson T. and Schultz J. (1939) Pentose nucleotides in the cytoplasm of growing tissues. Nature 143: 602–603.
    4.
    Brachet J. (1941) La localisation des acides pentosenucléiques dans les tissus animaux et les oeufs d‘amphibiens en voie de développement. Archives de Biologie 53: 207–257.
    5.
    Brachet J. (1941) La detection histochimique et la microdosage des acides pentosenucléiques. Enzymologia 10: 87–96.
    6.
    Caspersson T. (1941) Studien über den Eiweißumsatz der Zelle. Naturwissenschaften 29: 33–43.
    7.
    Claude A. (1938) Concentration and purification of chicken tumor I agent. Science 87: 467–468. [PubMed: 17788530]
    8.
    Claude A. (1943) The constitution of protoplasm. Science 97: 451–456. [PubMed: 17789864]
    9.
    Claude A. (1946) Fractionation of mammalian liver cells by differential centrifugation: I. Problems, methods, and preparation of extract. Journal of Experimental Medicine 84: 51–59. [PubMed: 20988750]
    10.
    Brachet J. (1950) The localization and the role of ribonucleic acid in the cell. Annals of the New York Academy of Sciences 50: 861–869.
    11.
    Palade G.E. and Siekevitz P. (1956) Liver microsomes - An integrated morphological and biochemical study. Journal of Biophysical and Biochemical Cytology 2: 171–200. [PMC free article: PMC2223971] [PubMed: 13319380]
    12.
    Roberts R.B. (1958) Introduction, in R.B. Roberts (ed.) Microsomal Particles and Protein Synthesis (Pergamon Press, New York).
    13.
    Brimacombe R., Stoffler G. and Wittmann H.G. (1978) Ribosome structure. Annual Review of Biochemistry 47: 217–249. [PubMed: 354495]
    14.
    Marko A.M. and Butler G.C. (1951) The isolation of sodium desoxyribonucleate with sodium dodecyl sulfate. Journal of Biological Chemistry 190: 165–176. [PubMed: 14841162]
    15.
    Colter J.S. and Brown R.A. (1956) Preparation of nucleic acids from Ehrlich ascites tumor cells. Science 124: 1077–1078. [PubMed: 13380422]
    16.
    Georgiev G.P., Samarina O.P., Lerman M.I., Smirnov M.N. and Severtzov A.N. (1963) Biosynthesis of messenger and ribosomal ribonucleic acids in the nucleolochromosomal apparatus of animal cells. Nature 200: 1291–1294. [PubMed: 14098472]
    17.
    Holley R.W., Apgar J. and Merrill S.H. (1961) Evidence for the liberation of a nuclease from human fingers. Journal of Biological Chemistry 236: PC42–3. [PubMed: 13715349]
    18.
    Parks M.M., et al. (2018) Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression. Science Advances 4: eaao0665. [PMC free article: PMC5829973] [PubMed: 29503865]
    19.
    Guimaraes J.C. and Zavolan M. (2016) Patterns of ribosomal protein expression specify normal and malignant human cells. Genome Biology 17: article 236. [PMC free article: PMC5123215] [PubMed: 27884178]
    20.
    Panda A., et al. (2020) Tissue- and development-stage–specific mRNA and heterogeneous CNV signatures of human ribosomal proteins in normal and cancer samples. Nucleic Acids Research 48: 7079–7098. [PMC free article: PMC7367157] [PubMed: 32525984]
    21.
    Siekevitz P. and Zamecnik P.C. (1981) Ribosomes and protein synthesis. Journal of Cell Biology 91: 53s–65s. [PMC free article: PMC2112782] [PubMed: 7033244]
    22.
    Jacob F. (1988) The Statue Within: An Autobiography (Basic Books, New York).
    23.
    Carroll S.B. (2013) Brave Genius: A Scientist, a Philosopher, and Their Daring Adventures from the French Resistance to the Nobel Prize (Crown Publishers, New York).
    24.
    Cobb M. (2015) Who discovered messenger RNA? Current Biology 25: R526–32. [PubMed: 26126273]
    25.
    Caldwell P.C. and Hinshelwood C. (1950) Some considerations on autosynthesis in bacteria. Journal of the Chemical Society 1950: 3156–3159.
    26.
    Pauling L., Itano H.A., Singer S.J. and Wells I.C. (1949) Sickle cell anemia, a molecular disease. Science 110: 543–548. [PubMed: 15395398]
    27.
    Hunt J.A. and Ingram V.M. (1958) Allelomorphism and the chemical differences of the human haemoglobins A, S and C. Nature 181: 1062–1063. [PubMed: 13541361]
    28.
    Ingram V.M. (1958) Abnormal human haemoglobins. Proceedings of the Royal Society of Medicine 51: 645–646. [PubMed: 13578968]
    29.
    Hardison R.C., et al. (2002) HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Human Mutation 19: 225–233. [PubMed: 11857738]
    30.
    Giardine B., et al. (2011) Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach. Nature Genetics 43: 295–301. [PMC free article: PMC3878152] [PubMed: 21423179]
    31.
    Prescott D.M. and Mazia D. (1954) The permeability of nucleated and enucleated fragments of Amoeba proteus to D2O. Experimental Cell Research 6: 117–126. [PubMed: 13141989]
    32.
    Boivin A. and Vendrely R. (1947) Sur le rôle possible des deux acides nucléiques dans la cellule vivante. Experientia 3: 32–34. [PubMed: 20239698]
    33.
    Dounce A.L. (1952) Duplicating mechanism for peptide chain and nucleic acid synthesis. Enzymologia 15: 251–258. [PubMed: 13033864]
    34.
    Dounce A.L. (1953) Nucleic acid template hypotheses. Nature 172: 541. [PubMed: 13099258]
    35.
    Work T.S. and Campbell P.N. (1953) Nucleic acid template hypotheses. Nature 172: 541–542. [PubMed: 13099258]
    36.
    Rich A. and Watson J.D. (1954) Some relations between DNA and RNA. Proceedings of the National Academy of Sciences USA 40: 759–764. [PMC free article: PMC534159] [PubMed: 16589555]
    37.
    Brachet J.L.A. (1960) The Biological Role of Ribonucleic Acids. Sixth Weizmann Memorial Lecture Series (Elsevier, New York).
    38.
    Watson J.D. (1963) Involvement of RNA in synthesis of proteins. Science 140: 17–26. [PubMed: 13999211]
    39.
    Brenner S. (1957) On the impossibility of all overlapping triplet codes in information transfer from nucleic acid to proteins. Proceedings of the National Academy of Sciences USA 43: 687–694. [PMC free article: PMC528521] [PubMed: 16590069]
    40.
    Crick F.H. (1958) On protein synthesis. Symposia of the Society for Experimental Biology 12: 138–163. [PubMed: 13580867]
    41.
    Hoagland M.B., Stephenson M.L., Scott J.F., Hecht L.I. and Zamecnik P.C. (1958) Soluble ribonucleic acid intermediate in protein synthesis. Journal of Biological Chemistry 231: 241–257. [PubMed: 13538965]
    42.
    Twort F.W. (1915) An investigation on the nature of ultra-microscopic viruses. Lancet 186: 1241–1243. [PMC free article: PMC2170983] [PubMed: 20475326]
    43.
    D‘Herelle F. (2007) On an invisible microbe antagonistic toward dysenteric bacilli. Research in Microbiology 158: 553–554. [PubMed: 17855060]
    44.
    Cairns J. and Watson J.D. (2007) Phage and the Origins of Molecular Biology (Cold Spring Harbor Laboratory Press, New York).
    45.
    Pardee A.B. (1954) Nucleic acid precursors and protein synthesis. Proceedings of the National Academy of Sciences USA 40: 263–270. [PMC free article: PMC534118] [PubMed: 16589470]
    46.
    Jacob F. and Monod J. (1961) Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology 3: 318–356. [PubMed: 13718526]
    47.
    Brenner S., Jacob F. and Meselson M. (1961) An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature 190: 576–581. [PubMed: 20446365]
    48.
    Hershey A.D., Dixon J. and Chase M. (1953) Nucleic acid economy in bacteria infected with bacteriophage T2. I. Purine and pyrimidine composition. Journal of General Physiology 36: 777–789. [PMC free article: PMC2147416] [PubMed: 13069681]
    49.
    Volkin E. and Astrachan L. (1956) Phosphorus incorporation in Escherichia coli ribonucleic acid after infection with bacteriophage T2. Virology 2: 149–161. [PubMed: 13312220]
    50.
    Pardee A.B., Jacob F. and Monod J. (1959) The genetic control and cytoplasmic expression of “Inducibility” in the synthesis of β-galactosidase by E. coli. Journal of Molecular Biology 1: 165–178.
    51.
    Pardee A.B. (1985) Roots: Molecular basis of gene expression: Origins from the Pajama experiment. BioEssays 2: 86–89.
    52.
    Nomura M., Hall B.D. and Spiegelman S. (1960) Characterization of RNA synthesized in Escherichia coli after bacteriophage T2 infection. Journal of Molecular Biology 2: 306–326.
    53.
    Spiegelman S., Hall B.D. and Storck R. (1961) The occurrence of natural DNA-RNA complexes in E. coli infected with T2. Proceedings of the National Academy of Sciences USA 47: 1135–1141. [PMC free article: PMC223110] [PubMed: 16590863]
    54.
    Hall B.D. and Spiegelman S. (1961) Sequence complementarity of T2-DNA and T2-specific RNA. Proceedings of the National Academy of Sciences USA 47: 137–146. [PMC free article: PMC221635] [PubMed: 13710749]
    55.
    Gros F., et al. (1961) Unstable ribonucleic acid revealed by pulse labelling of Escherichia coli. Nature 190: 581–585. [PubMed: 13708983]
    56.
    Weiss S.B. and Gladstone L. (1959) A mammalian system for the incorporation of cytidine triphosphate into ribonucleic acid. Journal of the American Chemical Society 81: 4118–4119.
    57.
    Stevens A. (1960) Incorporation of the adenine ribonucleotide into RNA by cell fractions from E. coli B. Biochemical and Biophysical Research Communications 3: 92–96.
    58.
    Allfrey V.G. and Mirsky A.E. (1962) Evidence for complete DNA-dependence of RNA synthesis in isolated thymus nuclei. Proceedings of the National Academy of Sciences USA 48: 1590–1596. [PMC free article: PMC221004] [PubMed: 13860598]
    59.
    Olby R. (1994) The Path to the Double Helix: The Discovery of DNA (Dover Publications, New York).
    60.
    Kay L. (2000) Who Wrote the Book of Life? A History of the Genetic Code (Stanford University Press, New York).
    61.
    Strauss B.S. (2019) Martynas Yčas: The “Archivist” of the RNA tie club. Genetics 211: 789–795. [PMC free article: PMC6404253] [PubMed: 30846543]
    62.
    Cobb M. (2016) Life’s Greatest Secret: The Race to Crack the Genetic Code (Profile Books, New York).
    63.
    Shannon C.E. (1940) An algebra for theoretical genetics. PhD thesis, Massachusetts Institute of Technology.
    64.
    Shannon C.E. (1948) A mathematical theory of communication. Bell System Technical Journal 27: 379–423.
    65.
    Shannon C.E. and Weaver W. (1949) A Mathematical Theory of Communication (University of Illinois Press, New York).
    66.
    Wiener N. (1948) Cybernetics: Or Control and Communication in the Animal and the Machine (2nd revised ed. 1961). (MIT Press, New York).
    67.
    Mayr E. (1961) Cause and effect in biology. Science 134: 1501–1506. [PubMed: 14471768]
    68.
    Sanger F. and Tuppy H. (1951) The amino-acid sequence in the phenylalanyl chain of insulin. I. The identification of lower peptides from partial hydrolysates. Biochemical Journal 49: 463–481. [PMC free article: PMC1197535] [PubMed: 14886310]
    69.
    Sanger F. and Tuppy H. (1951) The amino-acid sequence in the phenylalanyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates. Biochemical Journal 49: 481–490. [PMC free article: PMC1197536] [PubMed: 14886311]
    70.
    Sanger F. and Thompson E.O.P. (1953) The amino-acid sequence in the glycyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates. Biochemical Journal 53: 353–366. [PMC free article: PMC1198157] [PubMed: 13032078]
    71.
    Sanger F. and Thompson E.O.P. (1953) The amino-acid sequence in the glycyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates. Biochemical Journal 53: 366–374. [PMC free article: PMC1198158] [PubMed: 13032079]
    72.
    Benzer S. (1957) The elementary units of heredity, in W. D. McElroy and B. Glass (eds.) A Symposium on The Chemical Basis of Heredity (Johns Hopkins University Press, New York).
    73.
    Benzer S. (1959) On the topology of the genetic fine structure. Proceedings of the National Academy of Sciences USA 45: 1607–1620. [PMC free article: PMC222769] [PubMed: 16590553]
    74.
    Benzer S. (1960) Genetic fine structure. Harvey Lectures 56: 1–21. [PubMed: 13867418]
    75.
    Benzer S. (1961) On the topography of the genetic fine structure. Proceedings of the National Academy of Sciences USA 47: 403–415. [PMC free article: PMC221592] [PubMed: 16590840]
    76.
    Benzer S. (1962) The fine structure of the gene. Scientific American 206: 70–84. [PubMed: 13867419]
    77.
    Hayes W. (1968) The Genetics of Bacteria and Their Viruses (2nd edition). (Blackwell Scientific Publications, New York).
    78.
    Harris W.A. (2008) Seymour Benzer 1921–2007 The man who took us from genes to behaviour. PLOS Biology 6: e41.
    79.
    Benzer S. (1957) The elementary units of heredity, in W. D. McElroy and B. Glass (eds.) The Chemical Basis of Heredity (Johns Hopkins Press, New York).
    80.
    Yanofsky C. (2007) Establishing the triplet nature of the genetic code. Cell 128: 815–818. [PubMed: 17350564]
    81.
    Crick F.H., Barnett L., Brenner S. and Watts-Tobin R.J. (1961) General nature of the genetic code for proteins. Nature 192: 1227–1232. [PubMed: 13882203]
    82.
    Tsugita A. and Fraenkel-Conrat H. (1960) The amino acid composition and C-terminal sequence of a chemically evoked mutant of Tmv. Proceedings of the National Academy of Sciences USA 46: 636–642. [PMC free article: PMC222886] [PubMed: 16590652]
    83.
    Crick F.H.C. (1966) Codon—anticodon pairing: The wobble hypothesis. Journal of Molecular Biology 19: 548–555. [PubMed: 5969078]
    84.
    Crick F.H., Griffith J.S. and Orgel L.E. (1957) Codes without commas. Proceedings of the National Academy of Sciences USA 43: 416–421. [PMC free article: PMC528468] [PubMed: 16590032]
    85.
    Nirenberg M.W. and Matthaei J.H. (1961) The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides. Proceedings of the National Academy of Sciences USA 47: 1588–1602. [PMC free article: PMC223178] [PubMed: 14479932]
    86.
    Matthaei J.H., Jones O.W., Martin R.G. and Nirenberg M.W. (1962) Characteristics and composition of RNA coding units. Proceedings of the National Academy of Sciences USA 48: 666–677. [PMC free article: PMC220831] [PubMed: 14471390]
    87.
    Leder P. and Nirenberg M. (1964) RNA codewords and protein synthesis II. Nucleotide sequence of a valine RNA codeword. Proceedings of the National Academy of Sciences USA 52: 420–427. [PMC free article: PMC300293] [PubMed: 14206609]
    88.
    Nirenberg M., et al. (1965) RNA codewords and protein synthesis VII. On the general nature of the RNA code. Proceedings of the National Academy of Sciences USA 53: 1161–1168. [PMC free article: PMC301388] [PubMed: 5330357]
    89.
    Nirenberg M., et al. (1966) The RNA code and protein synthesis. Cold Spring Harbor Symposia on Quantitative Biology 31: 11–24. [PubMed: 5237186]
    90.
    Crick F.H.C. (1966) Genetic code - yesterday today and tomorrow. Cold Spring Harbor Symposia on Quantitative Biology 31: 3–9. [PubMed: 5237190]
    91.
    Marshall J. (2014) The genetic code. Proceedings of the National Academy of Sciences USA 111: 5760. [PMC free article: PMC4000838] [PubMed: 24756940]
    92.
    Lwoff A.M. (1977) Jacques Lucien Monod, 9 February 1910–31 May 1976. Biographical Memoirs of Fellows of the Royal Society 23: 385–412. [PubMed: 11615735]
    93.
    Stedman E. and Stedman E. (1950) Cell specificity of histones. Nature 166: 780–781. [PubMed: 14780242]
    94.
    McClintock B. (1956) Controlling elements and the gene. Cold Spring Harbor Symposia on Quantitative Biology 21: 197–216. [PubMed: 13433592]
    95.
    Comfort N.C. (2003) The Tangled Field: Barbara McClintock’s Search for the Patterns of Genetic Control (Harvard University Press, New York).
    96.
    Rich A. and Davies D.R. (1956) A new two-stranded helical structure: Polyadenylic acid and polyuridylic acid. Journal of the American Chemical Society 78: 3548–3549.
    97.
    Rich A. (1960) A hybrid helix containing both deoxyribose and ribose polynucleotides and its relation to the transfer of information between the nucleic acids. Proceedings of the National Academy of Sciences USA 46: 1044–1053. [PMC free article: PMC222998] [PubMed: 16590711]
    98.
    Rich A. (2004) The excitement of discovery. Annual Review of Biochemistry 73: 1–37. [PubMed: 15189135]
    99.
    Fedoroff N., Wellauer P.K. and Wall R. (1977) Intermolecular duplexes in heterogeneous nuclear RNA from HeLa cells. Cell 10: 597–610. [PubMed: 862021]
    100.
    Calvet J.P. and Pederson T. (1981) Base-pairing interactions between small nuclear RNAs and nuclear RNA precursors as revealed by psoralen cross-linking in vivo. Cell 26: 363–370. [PubMed: 6173132]
    101.
    Lu Z. and Chang H.Y. (2018) The RNA base-pairing problem and base-pairing solutions. Cold Spring Harbor Perspectives in Biology 10: a034926. [PMC free article: PMC6280703] [PubMed: 30510063]
    102.
    Felsenfeld G., Davies D.R. and Rich A. (1957) Formation of a three-stranded polynucleotide molecule. Journal of the American Chemical Society 79: 2023–2024.
    103.
    Hoogsteen K. (1963) The crystal and molecular structure of a hydrogen-bonded complex between 1-methylthymine and 9-methyladenine. Acta Crystallographica 16: 907–916.
    104.
    Rich A. and RajBhandary U.L. (1976) Transfer RNA: Molecular structure, sequence, and properties. Annual Review of Biochemistry 45: 805–860. [PubMed: 60910]
    105.
    Sanger F., Brownlee G.G. and Barrell B.G. (1965) A two-dimensional fractionation procedure for radioactive nucleotides. Journal of Molecular Biology 13: 373–398. [PubMed: 5325727]
    106.
    Holley R.W., et al. (1965) Structure of a ribonucleic acid. Science 147: 1462–1465. [PubMed: 14263761]
    107.
    Hori H. (2014) Methylated nucleosides in tRNA and tRNA methyltransferases. Frontiers in Genetics 5: 144. [PMC free article: PMC4033218] [PubMed: 24904644]
    108.
    Kim S.H., et al. (1974) Three-dimensional tertiary structure of yeast phenylalanine transfer RNA. Science 185: 435–440. [PubMed: 4601792]
    109.
    Robertus J.D., et al. (1974) Structure of yeast phenylalanine tRNA at 3 Å resolution. Nature 250: 546–551. [PubMed: 4602655]
    110.
    Kim S.H., et al. (1974) The general structure of transfer RNA molecules. Proceedings of the National Academy of Sciences USA 71: 4970–4974. [PMC free article: PMC434021] [PubMed: 4612535]
    111.
    Barciszewska M.Z., Perrigue P.M. and Barciszewski J. (2016) tRNA – the golden standard in molecular biology. Molecular BioSystems 12: 12–17. [PubMed: 26549858]
    112.
    Suzuki T. (2021) The expanding world of tRNA modifications and their disease relevance. Nature Reviews Molecular Cell Biology 22: 375–392. [PubMed: 33658722]
    113.
    Stout C.D., et al. (1976) Atomic coordinates and molecular conformation of yeast phenylalanyl tRNA. An independent investigation. Nucleic Acids Research 3: 1111–1123. [PMC free article: PMC342970] [PubMed: 775444]
    114.
    Holbrook S.R., Sussman J.L., Warrant R.W. and Kim S.-H. (1978) Crystal structure of yeast phenylalanine transfer RNA II: Structural features and functional implications. Journal of Molecular Biology 123: 631–660. [PubMed: 357743]
    115.
    Westhof E. and Fritsch V. (2000) RNA folding: Beyond Watson–Crick pairs. Structure 8: R55–65. [PubMed: 10745012]
    116.
    Leontis N.B., Lescoute A. and Westhof E. (2006) The building blocks and motifs of RNA architecture. Current Opinion in Structural Biology 16: 279–287. [PMC free article: PMC4857889] [PubMed: 16713707]
    117.
    Pardee A.B. and Prestidge L.S. (1959) On the nature of the repressor of beta-galactosidase synthesis in Escherichia coli. Biochimica and Biophysica Acta 36: 545–547. [PubMed: 14430363]
    118.
    Szilard L. (1960) The control of the formation of specific proteins in bacteria and in animal cells. Proceedings of the National Academy of Sciences USA 46: 277–292. [PMC free article: PMC222829] [PubMed: 16578481]
    119.
    Rich A. (1961) The transfer of information between the nucleic acids, in D. Rudnick (ed.) Molecular and Cellular Synthesis (Ronald Press, New York).
    120.
    Paigen K. (1962) On regulation of DNA transcription. Journal of Theoretical Biology 3: 268–282.
    121.
    Sypherd P.S. and Strauss N. (1963) The role of RNA in repression of enzyme synthesis. Proceedings of the National Academy of Sciences USA 50: 1059–1066. [PMC free article: PMC221274] [PubMed: 14096178]
    122.
    Leppek K., et al. (2020) Gene- and species-specific Hox mRNA translation by ribosome expansion segments. Molecular Cell 80: 980–995. [PMC free article: PMC7769145] [PubMed: 33202249]
    123.
    Monod J. and Jacob F. (1961) General conclusions: Teleonomic mechanisms in cellular metabolism, growth, and differentiation. Cold Spring Harbor Symposia on Quantitative Biology 26: 389–401. [PubMed: 14475415]
    124.
    Monod J., Changeux J.P. and Jacob F. (1963) Allosteric proteins and cellular control systems. Journal of Molecular Biology 6: 306–329. [PubMed: 13936070]
    125.
    Monod J., Wyman J. and Changeux J.-P. (1965) On the nature of allosteric transitions: A plausible model. Journal of Molecular Biology 12: 88–118. [PubMed: 14343300]
    126.
    Stent G.S. (1964) The operon: On its third anniversary. Modulation of transfer RNA species can provide a workable model of an operator-less operon. Science 144: 816–820. [PubMed: 14149392]
    127.
    Gilbert W. and Muller-Hill B. (1966) Isolation of the lac repressor. Proceedings of the National Academy of Sciences USA 56: 1891–1898. [PMC free article: PMC220206] [PubMed: 16591435]
    128.
    Ptashne M. (1967) Isolation of the lambda phage repressor. Proceedings of the National Academy of Sciences USA 57: 306–313. [PMC free article: PMC335506] [PubMed: 16591470]
    129.
    Ptashne M. (1967) Specific binding of the lambda phage repressor to lambda DNA. Nature 214: 232–234. [PubMed: 6034235]
    130.
    Gilbert W. and Muller-Hill B. (1967) The lac operator is DNA. Proceedings of the National Academy of Sciences USA 58: 2415–2421. [PMC free article: PMC223851] [PubMed: 4873589]
    131.
    Englesberg E., Irr J., Power J. and Lee N. (1965) Positive control of enzyme synthesis by gene C in l-arabinose system. Journal of Bacteriology 90: 946–957. [PMC free article: PMC315760] [PubMed: 5321403]
    132.
    Hahn S. (2014) Ellis Englesberg and the discovery of positive control in gene regulation. Genetics 198: 455–460. [PMC free article: PMC4196604] [PubMed: 25316786]
    133.
    Dunn J.J. and Bautz E.K. (1969) DNA-dependent RNA polymerase from E. coli: Studies on the role of sigma in chain initiation. Biochemical and Biophysical Research Communications 36: 925–930. [PubMed: 4310148]
    134.
    Burgess R.R., Travers A.A., Dunn J.J. and Bautz E.K. (1969) Factor stimulating transcription by RNA polymerase. Nature 221: 43–46. [PubMed: 4882047]
    135.
    Reich P.R., Forget B.G. and Weissman S.M. (1966) RNA of low molecular weight in KB cells infected with adenovirus type 2. Journal of Molecular Biology 17: 428–439. [PubMed: 5963076]
    136.
    Hindley J. (1967) Fractionation of 32P-labelled ribonucleic acids on polyacrylamide gels and their characterization by fingerprinting. Journal of Molecular Biology 30: 125–136. [PubMed: 4865141]
    137.
    Wassarman K.M. and Storz G. (2000) 6S RNA regulates E. coli RNA polymerase activity. Cell 101: 613–623. [PubMed: 10892648]
    138.
    Ikemura T. and Dahlberg J.E. (1973) Small ribonucleic-acids of Escherichia coli I. Characterization by polyacrylamide-gel electrophoresis and fingerprint analysis. Journal of Biological Chemistry 248: 5024–5032. [PubMed: 4577761]
    139.
    Ikemura T. and Dahlberg J.E. (1973) Small ribonucleic-acids of Escherichia coli II. Noncoordinate accumulation during stringent control. Journal of Biological Chemistry 248: 5033–5041. [PubMed: 4577762]
    140.
    Møller T., Franch T., Udesen C., Gerdes K. and Valentin-Hansen P. (2002) Spot 42 RNA mediates discoordinate expression of the E. coli galactose operon. Genes & Development 16: 1696–1706. [PMC free article: PMC186370] [PubMed: 12101127]
    141.
    Beisel C.L. and Storz G. (2011) The base-pairing RNA Spot 42 participates in a multioutput feedforward loop to help enact catabolite repression in Escherichia coli. Molecular Cell 41: 286–97. [PMC free article: PMC3072601] [PubMed: 21292161]
    142.
    Wang X., Ji S.C., Jeon H.J., Lee Y. and Lim H.M. (2015) Two-level inhibition of galK expression by Spot 42: Degradation of mRNA mK2 and enhanced transcription termination before the galK gene. Proceedings of the National Academy of Sciences USA 112: 7581–7586. [PMC free article: PMC4475948] [PubMed: 26045496]
    143.
    Stretton A.O.W. (2002) The first sequence: Fred Sanger and insulin. Genetics 162: 527–532. [PMC free article: PMC1462286] [PubMed: 12399368]
    144.
    Edman P. (1950) Method for determination of amino acid seqence in peptides. Acta Chemica Scandinavica 4: 283–293.
    145.
    Edman P. and Begg G. (1967) A protein sequenator. European Journal of Biochemistry 1: 80–91. [PubMed: 6059350]
    146.
    Bragg L.W. (1913) The structure of some crystals as indicated by their diffraction of X-rays. Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences 89: 248–277.
    147.
    Thomas J.M. (2012) The birth of X-ray crystallography. Nature 491: 186–187. [PubMed: 23135450]
    148.
    Kendrew J.C., et al. (1958) A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature 181: 662–666. [PubMed: 13517261]
    149.
    Perutz M.F., et al. (1960) Structure of hæmoglobin: A three-dimensional Fourier synthesis at 5.5-Å resolution, obtained by X-ray analysis. Nature 185: 416–422. [PubMed: 18990801]
    150.
    Kendrew J.C., et al. (1960) Structure of myoglobin: A three-dimensional Fourier synthesis at 2 Å resolution. Nature 185: 422–427. [PubMed: 18990802]
    151.
    Kirk R. (2014) The first of its kind. Nature 511: 13.
    152.
    de Chadarevian S. (2018) John Kendrew and myoglobin: Protein structure determination in the 1950s. Protein Science 27: 1136–1143. [PMC free article: PMC5980623] [PubMed: 29607556]
    153.
    Wüthrich K. (2001) The way to NMR structures of proteins. Nature Structural Biology 8: 923–925. [PubMed: 11685234]
    154.
    Clore M.G. (2011) Adventures in biomolecular NMR, in D.M. Grant and R.K. Harris (eds.) Encyclopedia of Magnetic Resonance (John Wiley & Sons, New York).
    155.
    Nogales E. (2018) Profile of Joachim Frank, Richard Henderson, and Jacques Dubochet, 2017 Nobel laureates in chemistry. Proceedings of the National Academy of Sciences USA 115: 441–444. [PMC free article: PMC5777002] [PubMed: 29196527]
    156.
    Maier T., Leibundgut M., Boehringer D. and Ban N. (2010) Structure and function of eukaryotic fatty acid synthases. Quarterly Reviews of Biophysics 43: 373–422. [PubMed: 20731893]
    157.
    Murata K. and Wolf M. (2018) Cryo-electron microscopy for structural analysis of dynamic biological macromolecules. Biochimica et Biophysica Acta 1862: 324–334. [PubMed: 28756276]
    158.
    Benjin X. and Ling L. (2020) Developments, applications, and prospects of cryo-electron microscopy. Protein Science 29: 872–882. [PMC free article: PMC7096719] [PubMed: 31854478]
    159.
    Ho C.-M., et al. (2020) Bottom-up structural proteomics: CryoEM of protein complexes enriched from the cellular milieu. Nature Methods 17: 79–85. [PMC free article: PMC7494424] [PubMed: 31768063]
    160.
    Cobb M. (2017) 60 years ago, Francis Crick changed the logic of biology. PLOS Biology 15: e2003243. [PMC free article: PMC5602739] [PubMed: 28922352]
    161.
    Watson J.D., Gann A. and Witkowski J. (2012) Double Helix, Annotated and Ilustrated(Simon & Schuster, New York).
    162.
    Watson J.D. (1965) Molecular Biology of the Gene (Benjamin, New York).
    163.
    Crick F. (1970) Central dogma of molecular biology. Nature 227: 561–563. [PubMed: 4913914]
    164.
    Burness A.T.H., Vizoso A.D. and Clothier F.W. (1963) Encephalomyocarditis virus and its ribonucleic acid: Sedimentation characteristics: Sedimentation coefficients of encephalomyocarditis virus and its ribonucleic acid. Nature 197: 1177–1178. [PubMed: 14017133]
    165.
    Montagnier L. and Sanders F.K. (1963) Encephalomyocarditis virus and its ribonucleic acid: Sedimentation characteristics: Sedimentation properties of infective ribonucleic acid extracted from Encephalomyocarditis virus. Nature 197: 1178–1181.
    166.
    Montagnier L. and Sanders F.K. (1963) Replicative form of Encephalomyocarditis virus ribonucleic acid. Nature 199: 664–667. [PubMed: 14074552]
    167.
    Baltimore D., Becker Y. and Darnell J.E. (1964) Virus-specific double-stranded RNA in poliovirus-infected cells. Science 143: 1034–1036. [PubMed: 14107425]
    168.
    Weissmann C., Borst P., Burdon R.H., Billeter M.A. and Ochoa S. (1964) Replication of viral RNA. III. Double-stranded replicative form of MS2 phage RNA. Proceedings of the National Academy of Sciences USA 51: 682–690. [PMC free article: PMC300140] [PubMed: 14166775]
    169.
    Stern R. and Friedman R.M. (1970) Double-stranded RNA synthesized in animal cells in the presence of actinomycin D. Nature 226: 612–616. [PubMed: 5267046]
    170.
    Montagnier L. (1968) Presence of a double chain ribonucleic acid in animal cells. Comptes Rendus de l‘Académie des Sciences 267: 1417–1420. [PubMed: 4972977]
    171.
    Kolakofsky D. (2015) A short biased history of RNA viruses. RNA 21: 667–669. [PMC free article: PMC4371325] [PubMed: 25780183]
    172.
    Astier-Manifacier S. and Cornuet P. (1971) RNA-dependent RNA polymerase in Chinese cabbage. Biochimica et Biophysica Acta 232: 484–493. [PubMed: 5572618]
    173.
    Mattick J.S. and Mehler M.F. (2008) RNA editing, DNA recoding and the evolution of human cognition. Trends in Neuroscience 31: 227–233. [PubMed: 18395806]
    174.
    Boeke J.D., Garfinkel D.J., Styles C.A. and Fink G.R. (1985) Ty elements transpose through an RNA intermediate. Cell 40: 491–500. [PubMed: 2982495]
    175.
    Temin H.M. and Mizutani S. (1970) RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226: 1211–1213. [PubMed: 4316301]
    176.
    Baltimore D. (1970) Viral RNA-dependent DNA polymerase: RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226: 1209–1211. [PubMed: 4316300]
    177.
    Coffin J.M. and Fan H. (2016) The discovery of reverse transcriptase. Annual Review of Virology 3: 29–51. [PubMed: 27482900]
    178.
    Wood W.B. (1988) The Nematode Caenorhabditis Elegans (Cold Spring Harbor Laboratory, New York).
    179.
    Stent G.S. (1968) That was the molecular biology that was. Science 160: 390–395. [PubMed: 4868510]
    180.
    Brenner S. (1997) Centaur biology. Current Biology 7: R454.
    181.
    Friedmann H.C. (2004) From Butyribacterium to E. coli: An essay on unity in biochemistry. Perspectives in Biology and Medicine 47: 47–66. [PubMed: 15061168]

    Chapter 4

    1.
    Bianconi E., et al. (2013) An estimation of the number of cells in the human body. Annals of Human Biology 40: 463–471. [PubMed: 23829164]
    2.
    Sender R., Fuchs S. and Milo R. (2016) Revised estimates for the number of human and bacteria cells in the body. PLOS Biology 14: e1002533. [PMC free article: PMC4991899] [PubMed: 27541692]
    3.
    Williams R.W. and Herrup K. (1988) The control of neuron number. Annual Review of Neuroscience 11: 423–453. [PubMed: 3284447]
    4.
    Andersen B.B., Korbo L. and Pakkenberg B. (1992) A quantitative study of the human cerebellum with unbiased stereological techniques. Journal of Comparative Neurology 326: 549–560. [PubMed: 1484123]
    5.
    Azevedo F.A.C., et al. (2009) Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. Journal of Comparative Neurology 513: 532–541. [PubMed: 19226510]
    6.
    Levin P.A. and Angert E.R. (2015) Small but mighty: Cell size and bacteria. Cold Spring Harbor Perspectives in Biology 7: a019216. [PMC free article: PMC4484965] [PubMed: 26054743]
    7.
    Land M., et al. (2015) Insights from 20 years of bacterial genome sequencing. Functional & Integrative Genomics 15: 141–161. [PMC free article: PMC4361730] [PubMed: 25722247]
    8.
    Cairns J. (1963) The bacterial chromosome and its manner of replication as seen by autoradiography. Journal of Molecular Biology 6: 208–213. [PubMed: 14017761]
    9.
    Lederberg J. (1952) Cell genetics and hereditary symbiosis. Physiological Reviews 32: 403–430. [PubMed: 13003535]
    10.
    Yanofsky C. (1981) Attenuation in the control of expression of bacterial operons. Nature 289: 751–758. [PubMed: 7007895]
    11.
    Dacks J.B. and Field M.C. (2007) Evolution of the eukaryotic membrane-trafficking system: Origin, tempo and mode. Journal of Cell Science 120: 2977–2985. [PubMed: 17715154]
    12.
    Parton R.G. and del Pozo M.A. (2013) Caveolae as plasma membrane sensors, protectors and organizers. Nature Reviews Molecular Cell Biology 14: 98–112. [PubMed: 23340574]
    13.
    Naslavsky N. and Caplan S. (2018) The enigmatic endosome – sorting the ins and outs of endocytic trafficking. Journal of Cell Science 131: jcs216499. [PMC free article: PMC6051342] [PubMed: 29980602]
    14.
    Schrader M. and Fahimi H.D. (2008) The peroxisome: Still a mysterious organelle. Histochemistry and Cell Biology 129: 421–440. [PMC free article: PMC2668598] [PubMed: 18274771]
    15.
    de Duve C. (2005) The lysosome turns fifty. Nature Cell Biology 7: 847–849. [PubMed: 16136179]
    16.
    Xu H. and Ren D. (2015) Lysosomal physiology. Annual Review of Physiology 77: 57–80. [PMC free article: PMC4524569] [PubMed: 25668017]
    17.
    Perera R.M. and Zoncu R. (2016) The lysosome as a regulatory hub. Annual Review of Cell and Developmental Biology 32: 223–253. [PMC free article: PMC9345128] [PubMed: 27501449]
    18.
    Schwarz D.S. and Blower M.D. (2016) The endoplasmic reticulum: Structure, function and response to cellular signaling. Cellular and Molecular Life Sciences 73: 79–94. [PMC free article: PMC4700099] [PubMed: 26433683]
    19.
    Gallo A., Vannier C. and Galli T. (2016) Endoplasmic reticulum-plasma membrane associations: Structures and functions. Annual Review of Cell and Developmental Biology 32: 279–301. [PubMed: 27298092]
    20.
    Mellman I. and Simons K. (1992) The Golgi complex: In vitro veritas? Cell 68: 829–840. [PMC free article: PMC7133332] [PubMed: 1547485]
    21.
    Guo Y., Sirkis D.W. and Schekman R. (2014) Protein sorting at the trans-Golgi network. Annual Review of Cell and Developmental Biology 30: 169–206. [PubMed: 25150009]
    22.
    Golgi C. (1898) Intorno alla struttura delle cellule nervose. Bollettino della Società Medico-Chirurgica di Pavia 13: 316.
    23.
    Spinelli J.B. and Haigis M.C. (2018) The multifaceted contributions of mitochondria to cellular metabolism. Nature Cell Biology 20: 745–754. [PMC free article: PMC6541229] [PubMed: 29950572]
    24.
    Jensen P.E. and Leister D. (2014) Chloroplast evolution, structure and functions. F1000Prime Reports 6: 40. [PMC free article: PMC4075315] [PubMed: 24991417]
    25.
    Vance J.E. (1990) Phospholipid synthesis in a membrane fraction associated with mitochondria. Journal of Biological Chemistry 265: 7248–7256. [PubMed: 2332429]
    26.
    Kornmann B., et al. (2009) An ER-mitochondria tethering complex revealed by a synthetic biology screen. Science 325: 477–481. [PMC free article: PMC2933203] [PubMed: 19556461]
    27.
    Valm A.M., et al. (2017) Applying systems-level spectral imaging and analysis to reveal the organelle interactome. Nature 546: 162–167. [PMC free article: PMC5536967] [PubMed: 28538724]
    28.
    Wu Y., et al. (2017) Contacts between the endoplasmic reticulum and other membranes in neurons. Proceedings of the National Academy of Sciences USA 114: E4859–67. [PMC free article: PMC5474793] [PubMed: 28559323]
    29.
    Shai N., et al. (2018) Systematic mapping of contact sites reveals tethers and a function for the peroxisome-mitochondria contact. Nature Communications 9: 1761. [PMC free article: PMC5932058] [PubMed: 29720625]
    30.
    Islinger M., Godinho L., Costello J. and Schrader M. (2015) The different facets of organelle interplay—an overview of organelle interactions. Frontiers in Cell and Developmental Biology 3: 56. [PMC free article: PMC4585249] [PubMed: 26442263]
    31.
    Pederson T. (2011) The nucleolus. Cold Spring Harbor Perspectives in Biology 3: a000638. [PMC free article: PMC3039934] [PubMed: 21106648]
    32.
    Surovtsev I.V. and Jacobs-Wagner C. (2018) Subcellular organization: A critical feature of bacterial cell replication. Cell 172: 1271–1293. [PMC free article: PMC5870143] [PubMed: 29522747]
    33.
    Greening C. and Lithgow T. (2020) Formation and function of bacterial organelles. Nature Reviews Microbiology 18: 677–689. [PubMed: 32710089]
    34.
    Flechsler J., Heimerl T., Huber H., Rachel R. and Berg I.A. (2021) Functional compartmentalization and metabolic separation in a prokaryotic cell. Proceedings of the National Academy of Sciences USA 118: e2022114118. [PMC free article: PMC8237620] [PubMed: 34161262]
    35.
    Guo Q., et al. (2018) In situ structure of neuronal C9orf72 poly-GA aggregates reveals proteasome recruitment. Cell 172: 696–705. [PMC free article: PMC6035389] [PubMed: 29398115]
    36.
    Deniston C.K., et al. (2020) Structure of LRRK2 in Parkinson’s disease and model for microtubule interaction. Nature 588: 344–349. [PMC free article: PMC7726071] [PubMed: 32814344]
    37.
    Hoffman D.P., et al. (2020) Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells. Science 367: eaaz5357. [PMC free article: PMC7339343] [PubMed: 31949053]
    38.
    Tegunov D., Xue L., Dienemann C., Cramer P. and Mahamid J. (2021) Multi-particle cryo-EM refinement with M visualizes ribosome-antibiotic complex at 3.5 Å in cells. Nature Methods 18: 186–193. [PMC free article: PMC7611018] [PubMed: 33542511]
    39.
    Heinrich L., et al. (2021) Whole-cell organelle segmentation in volume electron microscopy. Nature 599: 141–146. [PubMed: 34616042]
    40.
    Schrödinger E. (1944) What Is Life? The Physical Aspect of the Living Cell (Cambridge Univ. Press, New York).
    41.
    Ball P. (2018) Schrödinger’s cat among biology’s pigeons: 75 years of What Is Life? Nature 560: 548–550.
    42.
    Russell M.J. and Hall A.J. (1997) The emergence of life from iron monosulphide bubbles at a submarine hydrothermal redox and pH front. Journal of the Geological Society 154: 377–402. [PubMed: 11541234]
    43.
    Barge L.M., Flores E., Baum M.M., VanderVelde D.G. and Russell M.J. (2019) Redox and pH gradients drive amino acid synthesis in iron oxyhydroxide mineral systems. Proceedings of the National Academy of Sciences USA 116: 4828–4833. [PMC free article: PMC6421445] [PubMed: 30804197]
    44.
    Lane N. (2015) The Vital Question: Why is Life the Way It Is? (Profile Books, New York).
    45.
    Cartwright J.H.E. and Russell M.J. (2019) The origin of life: The submarine alkaline vent theory at 30. The Royal Society Interface Focus 9: 20190104.
    46.
    Dodd M.S., et al. (2017) Evidence for early life in Earth’s oldest hydrothermal vent precipitates. Nature 543: 60–64. [PubMed: 28252057]
    47.
    Pearce B.K.D., Pudritz R.E., Semenov D.A. and Henning T.K. (2017) Origin of the RNA world: The fate of nucleobases in warm little ponds. Proceedings of the National Academy of Sciences USA 114: 11327–11332. [PMC free article: PMC5664528] [PubMed: 28973920]
    48.
    Kim H.-J., et al. (2011) Synthesis of carbohydrates in mineral-guided prebiotic cycles. Journal of the American Chemical Society 133: 9457–9468. [PubMed: 21553892]
    49.
    Mulkidjanian A.Y., Bychkov A.Y., Dibrova D.V., Galperin M.Y. and Koonin E.V. (2012) Origin of first cells at terrestrial, anoxic geothermal fields. Proceedings of the National Academy of Sciences USA 109: E821–30. [PMC free article: PMC3325685] [PubMed: 22331915]
    50.
    Van Kranendonk M.J., Deamer D.W. and Djokic T. (2017) Life springs. Scientific American 317: 28–35. [PubMed: 29565926]
    51.
    Djokic T., Van Kranendonk M.J., Campbell K.A., Walter M.R. and Ward C.R. (2017) Earliest signs of life on land preserved in ca. 3.5 Ga hot spring deposits. Nature Communications 8: 15263. [PMC free article: PMC5436104] [PubMed: 28486437]
    52.
    Forsythe J.G., et al. (2017) Surveying the sequence diversity of model prebiotic peptides by mass spectrometry. Proceedings of the National Academy of Sciences USA 114: E7652–9. [PMC free article: PMC5604043] [PubMed: 28847940]
    53.
    Yi R., et al. (2020) A continuous reaction network that produces RNA precursors. Proceedings of the National Academy of Sciences USA 117: 13267–13274. [PMC free article: PMC7306801] [PubMed: 32487725]
    54.
    Damer B. and Deamer D.W. (2020) The hot spring hypothesis for an origin of life. Astrobiology 20: 429–452. [PMC free article: PMC7133448] [PubMed: 31841362]
    55.
    Van Kranendonk M.J., et al. (2021) Elements for the origin of life on land: A deep-time perspective from the Pilbara Craton of Western Australia. Astrobiology 21: 39–59. [PubMed: 33404294]
    56.
    Galtier N., Tourasse N. and Gouy M. (1999) A nonhyperthermophilic common ancestor to extant life forms. Science 283: 220–221. [PubMed: 9880254]
    57.
    Patel A., et al. (2017) ATP as a biological hydrotrope. Science 356: 753–756. [PubMed: 28522535]
    58.
    Woese C.R. (1967) The Genetic Code the Molecular Basis for Genetic Expression (Harper, New York).
    59.
    Woese C.R. and Fox G.E. (1977) Phylogenetic structure of the prokaryotic domain: The primary kingdoms. Proceedings of the National Academy of Sciences USA 74: 5088–5090. [PMC free article: PMC432104] [PubMed: 270744]
    60.
    Woese C.R., Kandler O. and Wheelis M.L. (1990) Towards a natural system of organisms: Proposal for the domains Archaea, Bacteria, and Eucarya. Proceedings of the National Academy of Sciences USA 87: 4576–4579. [PMC free article: PMC54159] [PubMed: 2112744]
    61.
    Stanier R.Y. and Van Niel C.B. (1962) The concept of a bacterium. Archiv für Mikrobiologie 42: 17–35. [PubMed: 13916221]
    62.
    Sapp J. (2005) The prokaryote-eukaryote dichotomy: Meanings and mythology. Microbiology and Molecular Biology Reviews 69: 292–305. [PMC free article: PMC1197417] [PubMed: 15944457]
    63.
    Eme L., Sharpe S.C., Brown M.W. and Roger A.J. (2014) On the age of eukaryotes: Evaluating evidence from fossils and molecular clocks. Cold Spring Harbor Perspectives in Biology 6: a016139. [PMC free article: PMC4107988] [PubMed: 25085908]
    64.
    Margulis L. (1996) Archaeal-eubacterial mergers in the origin of Eukarya: Phylogenetic classification of life. Proceedings of the National Academy of Sciences USA 93: 1071–1076. [PMC free article: PMC40032] [PubMed: 8577716]
    65.
    Olsen G.J. and Woese C.R. (1997) Archaeal genomics: An overview. Cell 89: 991–994. [PubMed: 9215619]
    66.
    Koonin E.V. (2010) The origin and early evolution of eukaryotes in the light of phylogenomics. Genome Biology 11: 209. [PMC free article: PMC2898073] [PubMed: 20441612]
    67.
    Archibald J.M. (2015) Endosymbiosis and eukaryotic cell evolution. Current Biology 25: R911–21. [PubMed: 26439354]
    68.
    Eme L., Spang A., Lombard J., Stairs C.W. and Ettema T.J.G. (2017) Archaea and the origin of eukaryotes. Nature Reviews Microbiology 15: 711–723. [PubMed: 29123225]
    69.
    Zaremba-Niedzwiedzka K., et al. (2017) Asgard archaea illuminate the origin of eukaryotic cellular complexity. Nature 541: 353–358. [PubMed: 28077874]
    70.
    Mattiroli F., et al. (2017) Structure of histone-based chromatin in Archaea. Science 357: 609–612. [PMC free article: PMC5747315] [PubMed: 28798133]
    71.
    Brunk C.F. and Martin W.F. (2019) Archaeal histone contributions to the origin of eukaryotes. Trends in Microbiology 27: 703–714. [PubMed: 31076245]
    72.
    Imachi H., et al. (2020) Isolation of an archaeon at the prokaryote–eukaryote interface. Nature 577: 519–525. [PMC free article: PMC7015854] [PubMed: 31942073]
    73.
    Williams T.A., Cox C.J., Foster P.G., Szöllősi G.J. and Embley T.M. (2020) Phylogenomics provides robust support for a two-domains tree of life. Nature Ecology & Evolution 4: 138–147. [PMC free article: PMC6942926] [PubMed: 31819234]
    74.
    Stevens K.M., et al. (2020) Histone variants in archaea and the evolution of combinatorial chromatin complexity. Proceedings of the National Academy of Sciences USA 117: 33384–33395. [PMC free article: PMC7776873] [PubMed: 33288720]
    75.
    Colson P., et al. (2018) Ancestrality and mosaicism of giant viruses supporting the definition of the fourth TRUC of microbes. Frontiers in Microbiology 9: 2668. [PMC free article: PMC6277510] [PubMed: 30538677]
    76.
    Watson T. (2019) The trickster microbes that are shaking up the tree of life. Nature 569: 322–324. [PubMed: 31089235]
    77.
    Martin W. and Müller M. (1998) The hydrogen hypothesis for the first eukaryote. Nature 392: 37–41. [PubMed: 9510246]
    78.
    Doolittle W.F. (1998) A paradigm gets shifty. Nature 392: 15–16. [PubMed: 9510239]
    79.
    Cavalier-Smith T. (2002) Chloroplast evolution: Secondary symbiogenesis and multiple losses. Current Biology 12: R62–4. [PubMed: 11818081]
    80.
    McFadden G.I. and van Dooren G.G. (2004) Evolution: Red algal genome affirms a common origin of all plastids. Current Biology 14: R514–R6. [PubMed: 15242632]
    81.
    Sagan L. (1967) On the origin of mitosing cells. Journal of Theoretical Biology 14: 255–274. [PubMed: 11541392]
    82.
    Schwartz R.M. and Dayhoff M.O. (1978) Origins of prokaryotes, eukaryotes, mitochondria, and chloroplasts. Science 199: 395–403. [PubMed: 202030]
    83.
    Newton K.J. (1988) Plant mitochondrial genomes: Organization, expression and variation. Annual Review of Plant Physiology and Plant Molecular Biology 39: 503–532.
    84.
    Boore J.L. (1999) Animal mitochondrial genomes. Nucleic Acids Research 27: 1767–1780. [PMC free article: PMC148383] [PubMed: 10101183]
    85.
    Gray M.W. (2012) Mitochondrial evolution. Cold Spring Harbor Perspectives in Biology 4: a011403. [PMC free article: PMC3428767] [PubMed: 22952398]
    86.
    Daniell H., Lin C.S., Yu M. and Chang W.J. (2016) Chloroplast genomes: Diversity, evolution, and applications in genetic engineering. Genome Biology 17: 134. [PMC free article: PMC4918201] [PubMed: 27339192]
    87.
    Björkholm P., Harish A., Hagström E., Ernst A.M. and Andersson S.G.E. (2015) Mitochondrial genomes are retained by selective constraints on protein targeting. Proceedings of the National Academy of Sciences USA 112: 10154–10161. [PMC free article: PMC4547212] [PubMed: 26195779]
    88.
    Allen J.F. (2015) Why chloroplasts and mitochondria retain their own genomes and genetic systems: Colocation for redox regulation of gene expression. Proceedings of the National Academy of Sciences USA 112: 10231–10238. [PMC free article: PMC4547249] [PubMed: 26286985]
    89.
    Cavalier-Smith T. (1987) The origin of eukaryotic and archaebacterial cells. Annals of the New York Academy of Science 503: 17–54. [PubMed: 3113314]
    90.
    Cavalier-Smith T. (2009) Predation and eukaryote cell origins: A coevolutionary perspective. International Journal of Biochemistry and Cell Biology 41: 307–322. [PubMed: 18935970]
    91.
    McCauley D.E., Sundby A.K., Bailey M.F. and Welch M.E. (2007) Inheritance of chloroplast DNA is not strictly maternal in Silene vulgaris (Caryophyllaceae): Evidence from experimental crosses and natural populations. American Journal of Botany 94: 1333–1337. [PubMed: 21636500]
    92.
    Smith J.M. (1978) The Evolution of Sex (Cambridge University Press, New York).
    93.
    Morran L.T., Schmidt O.G., Gelarden I.A., Parrish 2nd R.C., and Lively C.M. (2011) Running with the Red Queen: Host-parasite coevolution selects for biparental sex. Science 333: 216–218. [PMC free article: PMC3402160] [PubMed: 21737739]
    94.
    Markov A.V. (2014) Horizontal gene transfer as a possible evolutionary predecessor of sexual reproduction. Paleontological Journal 48: 219–233.
    95.
    Speijer D., Lukes J. and Elias M. (2015) Sex is a ubiquitous, ancient, and inherent attribute of eukaryotic life. Proceedings of the National Academy of Sciences USA 112: 8827–8834. [PMC free article: PMC4517231] [PubMed: 26195746]
    96.
    Ishikawa F. and Naito T. (1999) Why do we have linear chromosomes? A matter of Adam and Eve. Mutation Research 434: 99–107. [PubMed: 10422538]
    97.
    Burgers P.M.J. and Kunkel T.A. (2017) Eukaryotic DNA replication fork. Annual Review of Biochemistry 86: 417–438. [PMC free article: PMC5597965] [PubMed: 28301743]
    98.
    Holliday R.A. (1964) A mechanism for gene conversion in fungi. Genetics Research 5: 282–304. [PubMed: 18976517]
    99.
    Holliday R. (1977) Recombination and meiosis. Philosophical Transactions of the Royal Society B: Biological Sciences 277: 359–370. [PubMed: 16297]
    100.
    Heyer W.-D., Ehmsen K.T. and Liu J. (2010) Regulation of homologous recombination in eukaryotes. Annual Review of Genetics 44: 113–139. [PMC free article: PMC4114321] [PubMed: 20690856]
    101.
    Cavalier-Smith T. (2002) Origins of the machinery of recombination and sex. Heredity 88: 125–141. [PubMed: 11932771]
    102.
    Zinder N.D. and Lederberg J. (1952) Genetic exchange in Salmonella. Journal of Bacteriology 64: 679–699. [PMC free article: PMC169409] [PubMed: 12999698]
    103.
    Parkinson J.S. (2016) Classic spotlight: The discovery of bacterial transduction. Journal of Bacteriology 198: 2899–2900. [PMC free article: PMC5055593] [PubMed: 27736750]
    104.
    Weiss R.A. (2006) The discovery of endogenous retroviruses. Retrovirology 3: 67. [PMC free article: PMC1617120] [PubMed: 17018135]
    105.
    Forterre P. (2006) The origin of viruses and their possible roles in major evolutionary transitions. Virus Research 117: 5–16. [PubMed: 16476498]
    106.
    Forterre P. (2006) Three RNA cells for ribosomal lineages and three DNA viruses to replicate their genomes: A hypothesis for the origin of cellular domain. Proceedings of the National Academy of Sciences USA 103: 3669–3674. [PMC free article: PMC1450140] [PubMed: 16505372]
    107.
    Koonin E.V., Senkevich T.G. and Dolja V.V. (2006) The ancient virus world and evolution of cells. Biology Direct 1: 29. [PMC free article: PMC1594570] [PubMed: 16984643]
    108.
    Koonin E.V. and Krupovic M. (2018) The depths of virus exaptation. Current Opinion in Virology 31: 1–8. [PubMed: 30071360]
    109.
    Krupovic M., Dolja V.V. and Koonin E.V. (2019) Origin of viruses: Primordial replicators recruiting capsids from hosts. Nature Reviews Microbiology 17: 449–458. [PubMed: 31142823]
    110.
    Quammen D. (2018) The Tangled Tree: A Radical New History of Life (Simon Schuster, New York). [PubMed: 30368655]
    111.
    Parfrey L.W., Lahr D.J.G., Knoll A.H. and Katz L.A. (2011) Estimating the timing of early eukaryotic diversification with multigene molecular clocks. Proceedings of the National Academy of Sciences USA 108: 13624–13629. [PMC free article: PMC3158185] [PubMed: 21810989]
    112.
    Strother P.K., Battison L., Brasier M.D. and Wellman C.H. (2011) Earth’s earliest non-marine eukaryotes. Nature 473: 505–509. [PubMed: 21490597]
    113.
    Knauth L.P. and Kennedy M.J. (2009) The late Precambrian greening of the Earth. Nature 460: 728–732. [PubMed: 19587681]
    114.
    Doyle J.A. (2012) Molecular and fossil evidence on the origin of Angiosperms. Annual Review of Earth and Planetary Sciences 40: 301–326.
    115.
    Consortium (2013) The Amborella genome and the evolution of flowering plants. Science 342: 1241089. [PubMed: 24357323]
    116.
    Leebens-Mack J.H. et al. (2019) One thousand plant transcriptomes and the phylogenomics of green plants. Nature 574: 679–685. [PMC free article: PMC6872490] [PubMed: 31645766]
    117.
    Osborne C.P. and Beerling D.J. (2006) Nature’s green revolution: The remarkable evolutionary rise of C4 plants. Philosophical Transactions of the Royal Society B: Biological Sciences 361: 173–194. [PMC free article: PMC1626541] [PubMed: 16553316]
    118.
    Turner E.C. (2021) Possible poriferan body fossils in early Neoproterozoic microbial reefs. Nature 596: 87–91. [PMC free article: PMC8338550] [PubMed: 34321662]
    119.
    Glaessner M.F. (1959) The oldest fossil faunas of South Australia. Geologische Rundschau 47: 522–531.
    120.
    Shen B., Dong L., Xiao S. and Kowalewski M. (2008) The Avalon explosion: Evolution of Ediacara morphospace. Science 319: 81–84. [PubMed: 18174439]
    121.
    Wainright P.O., Hinkle G., Sogin M.L. and Stickel S.K. (1993) Monophyletic origins of the metazoa: An evolutionary link with fungi. Science 260: 340–342. [PubMed: 8469985]
    122.
    Xiao S. and Laflamme M. (2009) On the eve of animal radiation: Phylogeny, ecology and evolution of the Ediacara biota. Trends in Ecology & Evolution 24: 31–40. [PubMed: 18952316]
    123.
    Chang Y., et al. (2015) Phylogenomic analyses indicate that early fungi evolved digesting cell walls of algal ancestors of land plants. Genome Biology and Evolution 7: 1590–1601. [PMC free article: PMC4494064] [PubMed: 25977457]
    124.
    Torruella G., et al. (2015) Phylogenomics reveals convergent evolution of lifestyles in close relatives of animals and fungi. Current Biology 25: 2404–2410. [PubMed: 26365255]
    125.
    Glaessner M.F. (1961) Pre-Cambrian animals. Scientific American 204: 72–78.
    126.
    McMenamin M.A. (1996) Ediacaran biota from Sonora, Mexico. Proceedings of the National Academy of Sciences USA 93: 4990–4993. [PMC free article: PMC39393] [PubMed: 11607679]
    127.
    Chen Z., Zhou C., Yuan X. and Xiao S. (2019) Death march of a segmented and trilobate bilaterian elucidates early animal evolution. Nature 573: 412–415. [PubMed: 31485079]
    128.
    Watson T. (2020) These bizarre ancient species are rewriting animal evolution. Nature 586: 662–665. [PubMed: 33116283]
    129.
    Evans S.D., Hughes I.V., Gehling J.G. and Droser M.L. (2020) Discovery of the oldest bilaterian from the Ediacaran of South Australia. Proceedings of the National Academy of Sciences USA 117: 7845–7850. [PMC free article: PMC7149385] [PubMed: 32205432]
    130.
    Conway-Morris S. (1993) Ediacaran-like fossils in Cambrian Burgess Shale-type faunas of North America. Palaeontology 36: 593–695.
    131.
    Jensen S., Gehling J.G. and Droser M.L. (1998) Ediacara-type fossils in Cambrian sediments. Nature 393: 567–569.
    132.
    Erwin D.H., et al. (2011) The Cambrian conundrum: Early divergence and later ecological success in the early history of animals. Science 334: 1091–1097. [PubMed: 22116879]
    133.
    Gehling J.G. and Droser M.L. (2018) Ediacaran scavenging as a prelude to predation. Emerging Topics in Life Sciences 2: 213–222. [PubMed: 32412628]
    134.
    Morris S.C. (1989) Burgess Shale faunas and the Cambrian Explosion. Science 246: 339–346. [PubMed: 17747916]
    135.
    Jablonski D. and Bottjer D.J. (1988) The ecology of evolutionary innovation - the fossil record, in 11th Annual Spring Systematics Symp - Evolutionary Innovations: Patterns and Processes, pp. 253–288.
    136.
    Caron J.-B. and Rudkin D. (2009) A Burgess Shale Primer - History, Geology, and Research Highlights (The Burgess Shale Consortium, New York).
    137.
    Peterson K.J., Dietrich M.R. and McPeek M.A. (2009) MicroRNAs and metazoan macroevolution: Insights into canalization, complexity, and the Cambrian explosion. BioEssays 31: 736–747. [PubMed: 19472371]
    138.
    Lee M.S.Y., Soubrier J. and Edgecombe G.D. (2013) Rates of phenotypic and genomic evolution during the Cambrian explosion. Current Biology 23: 1889–1895. [PubMed: 24035543]
    139.
    Caron J.-B., Gaines R.R., Aria C., Mángano M.G. and Streng M. (2014) A new phyllopod bed-like assemblage from the Burgess Shale of the Canadian Rockies. Nature Communications 5: 3210. [PubMed: 24513643]
    140.
    Peterson K.J., McPeek M.A. and Evans D.A.D. (2005) Tempo and mode of early animal evolution: Inferences from rocks, Hox, and molecular clocks. Paleobiology 31: 36–55.
    141.
    Benton M.J. (2005) Vertebrate Palaeontology (Blackwell, New York).
    142.
    Krug A.Z. and Jablonski D. (2012) Long-term origination rates are reset only at mass extinctions. Geology 40: 731–734.
    143.
    Kaiho K. and Oshima N. (2017) Site of asteroid impact changed the history of life on earth: The low probability of mass extinction. Scientific Reports 7: 14855. [PMC free article: PMC5680197] [PubMed: 29123110]
    144.
    Chiarenza A.A., et al. (2020) Asteroid impact, not volcanism, caused the end-Cretaceous dinosaur extinction. Proceedings of the National Academy of Sciences USA 117: 17084–17093. [PMC free article: PMC7382232] [PubMed: 32601204]
    145.
    Bozdag G.O., Libby E., Pineau R., Reinhard C.T. and Ratcliff W.C. (2021) Oxygen suppression of macroscopic multicellularity. Nature Communications 12: 2838. [PMC free article: PMC8121917] [PubMed: 33990594]
    146.
    Lyons T.W., Reinhard C.T. and Planavsky N.J. (2014) The rise of oxygen in Earth’s early ocean and atmosphere. Nature 506: 307–315. [PubMed: 24553238]
    147.
    Sperling E.A., et al. (2015) Statistical analysis of iron geochemical data suggests limited late Proterozoic oxygenation. Nature 523: 451–454. [PubMed: 26201598]
    148.
    Fox D. (2016) What sparked the Cambrian explosion? Nature 530: 268–270. [PubMed: 26887475]
    149.
    Raymond J. and Segrè D. (2006) The effect of oxygen on biochemical networks and the evolution of complex life. Science 311: 1764–1767. [PubMed: 16556842]
    150.
    Jabłońska J. and Tawfik D.S. (2021) The evolution of oxygen-utilizing enzymes suggests early biosphere oxygenation. Nature Ecology & Evolution 5: 442–448. [PubMed: 33633374]
    151.
    Butterfield N.J. (2009) Oxygen, animals and oceanic ventilation: An alternative view. Geobiology 7: 1–7. [PubMed: 19200141]
    152.
    Zhang S., et al. (2016) Sufficient oxygen for animal respiration 1,400 million years ago. Proceedings of the National Academy of Sciences USA 113: 1731. [PMC free article: PMC4763753] [PubMed: 26729865]
    153.
    Brown S.W. (1966) Heterochromatin. Science 151: 417–425. [PubMed: 5322971]
    154.
    Passarge E. (1979) Emil Heitz and the concept of heterochromatin: Longitudinal chromosome differentiation was recognized fifty years ago. American Journal of Human Genetics 31: 106–115. [PMC free article: PMC1685768] [PubMed: 377956]
    155.
    Zhimulev I.F., et al. (2004) Polytene chromosomes: 70 years of genetic research, in K. W. Jeon (ed.) International Review of Cytology (Academic Press, New York). [PubMed: 15548421]
    156.
    Eagen K.P., Hartl T.A. and Kornberg R.D. (2015) Stable chromosome condensation revealed by chromosome conformation capture. Cell 163: 934–946. [PMC free article: PMC4639323] [PubMed: 26544940]
    157.
    Heitz E. (1928) Das Heterochromatin der Moose. Jahrbücher für Wissenschaftliche Botanik 69: 762–818.
    158.
    Heitz E. (1933) Die somatische Heteropyknose bei Drosophila melanogaster und ihre genetische Bedeutung. Cell and Tissue Research 20: 237–287.
    159.
    Hsu T.C. (1962) Differential rate in RNA synthesis between euchromatin and heterochromatin. Experimental Cell Research 27: 332–334. [PubMed: 14449550]
    160.
    Poulson D.F. and Metz C.W. (1938) Studies on the structure of nucleolus-forming regions and related structures in the giant salivary gland chromosomes of Diptera. Journal of Morphology 63: 363–395.
    161.
    Beermann W. (1952) Chromomerenkonstanz und spezifische Modifikation der Chromosomenstruktur in der Entwicklung und Organdifferenzierung von Chironomus tentans. Chromosoma 5: 139–198. [PubMed: 13067187]
    162.
    Sass H. (1980) Features of in vitro puffing and RNA synthesis in polytene chromosomes of Chironomus. Chromosoma 78: 33–78. [PubMed: 6155245]
    163.
    Pavan C. and Breuer M.E. (1952) Polytene chromosomes: In different tissues of rhynchosciara. Journal of Heredity 43: 151–158.
    164.
    Breuer M.E. and Pavan C. (1955) Behavior of polytene chromosomes of Rhynchosciara angelae at different stages of larval development. Chromosoma 7: 371–386. [PubMed: 13250692]
    165.
    Ritossa F. (1962) New puffing pattern induced by temperature shock and DNP in drosophila. Experientia 18: 571–573.
    166.
    Stocker A.J. and Pavan C. (1974) The influence of ecdysterone on gene amplification, DNA synthesis, and puff formation in the salivary gland chromosomes of Rhynchosciara hollaenderi. Chromosoma 45: 295–319. [PubMed: 4837973]
    167.
    Beermann W. (1963) Cytological aspects of information transfer in cellular differentiation. American Zoologist 3: 23–32.
    168.
    Clever U. (1965) Puffing changes in incubated and in ecdysone treated Chironomus tentans salivary glands. Chromosoma 17: 309–322. [PubMed: 5885997]
    169.
    Clever U. (1965) Chromosomal changes associated with differentiation. Brookhaven Symposia in Biology 18: 242–253. [PubMed: 4170379]
    170.
    van Breugel F.M.A. (1966) Puff induction in larval salivary gland chromosomes of Drosophila hydei sturtevant. Genetica 37: 17–28. [PubMed: 5939566]
    171.
    Kroeger H. and Lezzi M. (1966) Regulation of gene action in insect development. Annual Review of Entomology 11: 1–22. [PubMed: 5321576]
    172.
    Jamrich M., Greenleaf A.L. and Bautz E.K. (1977) Localization of RNA polymerase in polytene chromosomes of Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 74: 2079–2083. [PMC free article: PMC431078] [PubMed: 405671]
    173.
    Graessmann A., Graessmann M. and Larat F.J.S. (1973) Involvement of RNA in the process of puff induction in polytene chromosomes, in B.A. Hamkalo and J. Papaconstantinou (eds.) Molecular Cytogenetics (Springer, New York).
    174.
    Lakhotia S.C. and Mukherjee T. (1982) Absence of novel translation products in relation to induced activity of the 93D puff in Drosophila melanogaster. Chromosoma 85: 369–374. [PubMed: 6811224]
    175.
    Lakhotia S.C. and Sharma A. (1996) The 93D (hsr-omega) locus of Drosophila: Non-coding gene with house-keeping functions. Genetica 97: 339–348. [PubMed: 9081862]
    176.
    Malik H.S. and Henikoff S. (2009) Major evolutionary transitions in centromere complexity. Cell 138: 1067–1082. [PubMed: 19766562]
    177.
    Talbert P.B. and Henikoff S. (2020) What makes a centromere? Experimental Cell Research 389: 111895. [PubMed: 32035948]
    178.
    Wunderlich V. (2002) JMM: Past and present. Chromosomes and cancer: Theodor Boveri’s predictions 100 years later. Journal of Molecular Medicine 80: 545–548. [PubMed: 12226736]
    179.
    Scheer U. (2014) Historical roots of centrosome research: Discovery of Boveri’s microscope slides in Würzburg. Philosophical Transactions of the Royal Society B: Biological Sciences 369: 20130469. [PMC free article: PMC4113113] [PubMed: 25047623]
    180.
    McKinley K.L. and Cheeseman I.M. (2016) The molecular basis for centromere identity and function. Nature Reviews Molecular Cell Biology 17: 16–29. [PMC free article: PMC8603311] [PubMed: 26601620]
    181.
    Ohno S., Kaplan W.D. and Kinosita R. (1959) Formation of the sex chromatin by a single X-chromosome in liver cells of Rattus norvegicus. Experimental Cell Research 18: 415–418. [PubMed: 14428474]
    182.
    Barr M.L. and Bertram E.G. (1949) A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature 163: 676–677. [PubMed: 18120749]
    183.
    Lyon M.F. (1961) Gene action in the X-chromosome of the mouse (Mus musculus). Nature 190: 372–373. [PubMed: 13764598]
    184.
    Lyon M.F. (1962) Sex chromatin and gene action in the mammalian X-chromosome. American Journal of Human Genetics 14: 135–148. [PMC free article: PMC1932279] [PubMed: 14467629]
    185.
    Centerwall W.R. and Benirschke K. (1973) Male Tortoiseshell and Calico (T-C) Cats: Animal models of sex chromosome mosaics, aneuploids, polyploids, and chimerics. Journal of Heredity 64: 272–278. [PubMed: 4798734]
    186.
    Basta M. and Pandya A.M. (2020) Genetics, X-linked inheritance, in StatPearls (StatPearls Publishing, New York). [PMC free article: PMC557383] [PubMed: 32491315]
    187.
    Dobyns W.B. et al. (2004) Inheritance of most X-linked traits is not dominant or recessive, just X-linked. American Journal of Medical Genetics 129A: 136–143. [PubMed: 15316978]
    188.
    Lucchesi J.C. (1973) Dosage compensation in Drosophila. Annual Review of Genetics 7: 225–237. [PubMed: 4205904]
    189.
    Brown S.W. and Nur U. (1964) Heterochromatic chromosomes in the Coccids. Science 145: 130–136. [PubMed: 14171547]
    190.
    Swift H. (1965) Molecular morphology of the chromosome. In Vitro 1: 26–49.
    191.
    Gall J.G. (1956) On the submicroscopic structure of chromosomes. Brookhaven Symposia in Biology 8: 17–32. [PubMed: 13293418]
    192.
    Singh G., Pratt G., Yeo G.W. and Moore M.J. (2015) The clothes make the mRNA: Past and present trends in mRNP fashion. Annual Review of Biochemistry 84: 325–354. [PMC free article: PMC4804868] [PubMed: 25784054]
    193.
    Flemming W. (1882) Zellsubstanz, Kern und Zelltheilung (Cell Substance, Nucleus and Cell Division) (F. C. W. Vogel, New York).
    194.
    Morgan G.T. (2002) Lampbrush chromosomes and associated bodies: New insights into principles of nuclear structure and function. Chromosome Research 10: 177–200. [PubMed: 12067208]
    195.
    Dinger M.E., Baillie G.J. and Musgrave D.R. (2000) Growth phase-dependent expression and degradation of histones in the thermophilic archaeon Thermococcus zilligii. Molecular Microbiology 36: 876–885. [PubMed: 10844675]
    196.
    Attar N., et al. (2020) The histone H3-H4 tetramer is a copper reductase enzyme. Science 369: 59–64. [PMC free article: PMC7842201] [PubMed: 32631887]
    197.
    Rudolph J. and Luger K. (2020) The secret life of histones. Science 369: 33. [PubMed: 32631882]
    198.
    Oudet P., Gross-Bellard M. and Chambon P. (1975) Electron microscopic and biochemical evidence that chromatin structure is a repeating unit. Cell 4: 281–300. [PubMed: 1122558]
    199.
    Kossel A. (1894) Uber einen peptonartigen bestandteil des zellkerns. Zeitschrift fur physiologische Chemie 8: 611–615.
    200.
    Olins A.L. and Olins D.E. (1974) Spheroid chromatin units (ν bodies). Science 183: 330–332. [PubMed: 4128918]
    201.
    Olins D.E. and Olins A.L. (1978) Nucleosomes: The structural quantum in chromosomes: Virtually all the DNA of eukaryotic cells is organized into a repeating array of nucleohistone particles called nucleosomes. These chromatin subunits are close-packed into higher-order fibers and are modified during chromosome expression. American Scientist 66: 704–711. [PubMed: 736351]
    202.
    Olins D.E. and Olins A.L. (2003) Chromatin history: Our view from the bridge. Nature Reviews Molecular Cell Biology 4: 809–814. [PubMed: 14570061]
    203.
    Kornberg R.D. (1974) Chromatin structure: A repeating unit of histones and DNA. Science 184: 868–871. [PubMed: 4825889]
    204.
    Kornberg R.D. and Thomas J.O. (1974) Chromatin structure; oligomers of the histones. Science 184: 865–868. [PubMed: 4825888]
    205.
    Stein G.S., Spelsberg T.C. and Kleinsmith L.J. (1974) Nonhistone chromosomal proteins and gene regulation. Science 183: 817–824. [PubMed: 4359338]
    206.
    Stedman E. and Stedman E. (1950) Cell specificity of histones. Nature 166: 780–781. [PubMed: 14780242]
    207.
    Huang R.C. and Bonner J. (1962) Histone, a suppressor of chromosomal RNA synthesis. Proceedings of the National Academy of Sciences USA 48: 1216–1222. [PMC free article: PMC220935] [PubMed: 14036409]
    208.
    Allfrey V.G., Littau V.C. and Mirsky A.E. (1963) On the role of of histones in regulation ribonucleic acid synthesis in the cell nucleus. Proceedings of the National Academy of Sciences USA 49: 414–421. [PMC free article: PMC299845] [PubMed: 14012159]
    209.
    Frenster J.H., Allfrey V.G. and Mirsky A.E. (1963) Repressed and active chromatin isolated from interphase lymphocytes. Proceedings of the National Academy of Sciences USA 50: 1026–1032. [PMC free article: PMC221266] [PubMed: 14096174]
    210.
    Littau V.C., Burdick C.J., Allfrey V.G. and Mirsky S.A. (1965) The role of histones in the maintenance of chromatin structure. Proceedings of the National Academy of Sciences USA 54: 1204–1212. [PMC free article: PMC219838] [PubMed: 5219825]
    211.
    Pardon J.F., Wilkins M.H. and Richards B.M. (1967) Super-helical model for nucleohistone. Nature 215: 508–509. [PubMed: 6057909]
    212.
    Pardon J.F. and Wilkins M.H. (1972) A super-coil model for nucleohistone. Journal of Molecular Biology 68: 115–124. [PubMed: 5050359]
    213.
    Allis C.D. (2015) “Modifying” my career toward chromatin biology. Journal of Biological Chemistry 290: 15904–15908. [PMC free article: PMC4481195] [PubMed: 25944906]
    214.
    Allfrey V.G. and Mirsky A.E. (1964) Structural modifications of histones and their possible role in the regulation of RNA synthesis. Science 144: 559. [PubMed: 17836360]
    215.
    Allfrey V.G., Faulkner R. and Mirsky A.E. (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proceedings of the National Academy of Sciences USA 51: 786–794. [PMC free article: PMC300163] [PubMed: 14172992]
    216.
    Pogo B.G., Allfrey V.G. and Mirsky A.E. (1966) RNA synthesis and histone acetylation during the course of gene activation in lymphocytes. Proceedings of the National Academy of Sciences USA 55: 805–812. [PMC free article: PMC224233] [PubMed: 5219687]
    217.
    Allfrey V.G., Pogo B.G., Littau V.C., Gershey E.L. and Mirsky A.E. (1968) Histone acetylation in insect chromosomes. Science 159: 314–316. [PubMed: 5634500]
    218.
    Riggs A.D. (1975) X inactivation, differentiation, and DNA methylation. Cytogenetics and Cell Genetics 14: 9–25. [PubMed: 1093816]
    219.
    Holliday R. and Pugh J.E. (1975) DNA modification mechanisms and gene activity during development. Science 187: 226–232. [PubMed: 1111098]
    220.
    Brownell J.E., et al. (1996) Tetrahymena histone acetyltransferase A: A homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84: 843–851. [PubMed: 8601308]
    221.
    Jones P.A. and Taylor S.M. (1980) Cellular differentiation, cytidine analogs and DNA methylation. Cell 20: 85–93. [PubMed: 6156004]
    222.
    Bird A., Taggart M., Frommer M., Miller O.J. and Macleod D. (1985) A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell 40: 91–99. [PubMed: 2981636]
    223.
    Bird A.P. (1986) CpG-rich islands and the function of DNA methylation. Nature 321: 209–213. [PubMed: 2423876]
    224.
    Brachet J. (1941) La detection histochimique et la microdosage des acides pentosenucléiques. Enzymologia 10: 87–96.
    225.
    Brachet J. (1950) The localization and the role of ribonucleic acid in the cell. Annals of the New York Academy of Sciences 50: 861–869.
    226.
    Mirsky A.E. and Ris H. (1947) The chemical composition of isolated chromosomes. Journal of General Physiology 31: 7–18. [PMC free article: PMC2147087] [PubMed: 19873520]
    227.
    Feinendegen L.E. and Bond V.P. (1963) Observations on nuclear RNA during mitosis in human cancer cells in culture (HeLa-S3), studied with tritiated cytidine. Experimental Cell Research 30: 393–404. [PubMed: 13962747]
    228.
    Edström J.-E. (1964) Chromosomal RNA and other nuclear RNA fractions, in M. Locke (ed.) The Role of Chromosomes in Development (Academic Press, New York).
    229.
    Frenster J.H. (1965) A model of specific de-repression within interphase chromatin. Nature 206: 1269–1270. [PubMed: 5879798]
    230.
    Frenster J.H. (1965) Nuclear polyanions as de-repressors of synthesis of ribonucleic acid. Nature 206: 680–683. [PubMed: 5832851]
    231.
    Huang R.C. and Bonner J. (1965) Histone-bound RNA, a component of native nucleohistone. Proceedings of the National Academy of Sciences USA 54: 960–967. [PMC free article: PMC219771] [PubMed: 5217473]
    232.
    Prestayko A.W. and Busch H. (1968) Low molecular weight RNA of the chromatin fraction from Novikoff hepatoma and rat liver nuclei. Biochimica et Biophysica Acta 169: 327–337. [PubMed: 4302868]
    233.
    Huang R.C. and Huang P.C. (1969) Effect of protein-bound RNA associated with chick embryo chromatin on template specificity of the chromatin. Journal of Molecular Biology 39: 365–378. [PubMed: 5362674]
    234.
    Dahmus M.E. and McConnell D.J. (1969) Chromosomal ribonucleic acid of rat ascites cells. Biochemistry 8: 1524–1534. [PubMed: 5805295]
    235.
    Bekhor I., Bonner J. and Dahmus G.K. (1969) Hybridization of chromosomal RNA to native DNA. Proceedings of the National Academy of Sciences USA 62: 271–277. [PMC free article: PMC285983] [PubMed: 5253662]
    236.
    Holmes D.S., Mayfield J.E., Sander G. and Bonner J. (1972) Chromosomal RNA: Its properties. Science 177: 72–74. [PubMed: 5041779]
    237.
    Bonner J. and Widholm J. (1967) Molecular complementarity between nuclear DNA and organ-specific chromosomal RNA. Proceedings of the National Academy of Sciences USA 57: 1379–1385. [PMC free article: PMC224483] [PubMed: 5231744]
    238.
    Bonner J., et al. (1968) The biology of isolated chromatin: Chromosomes, biologically active in the test tube, provide a powerful tool for the study of gene action. Science 159: 47–56. [PubMed: 4864031]
    239.
    Mayfield J.E. and Bonner J. (1971) Tissue differences in rat chromosomal RNA. Proceedings of the National Academy of Sciences USA 68: 2652–2655. [PMC free article: PMC389493] [PubMed: 5288240]
    240.
    Weinberg R.A. and Penman S. (1968) Small molecular weight monodisperse nuclear RNA. Journal of Molecular Biology 38: 289–304. [PubMed: 5718554]
    241.
    Jacobson R.A. and Bonner J. (1968) The occurrence of dihydro ribothymidine in chromosomal RNA. Biochemical and Biophysical Research Communications 33: 716–720. [PubMed: 5723333]
    242.
    Sivolap Y.M. and Bonner J. (1971) Association of chromosomal RNA with repetitive DNA. Proceedings of the National Academy of Sciences USA 68: 387–389. [PMC free article: PMC388944] [PubMed: 5277090]
    243.
    Holmes D.S., Mayfield J.E. and Bonner J. (1974) Sequence composition of rat ascites chromosomal ribonucleic acid. Biochemistry 13: 849–855. [PubMed: 4360352]
    244.
    Benjamin W., Levander O.A., Gellhorn A. and DeBellis R.H. (1966) An RNA-histone complex in mammalian cells: The isolation and characterization of a new RNA species. Proceedings of the National Academy of Sciences USA 55: 858–865. [PMC free article: PMC224242] [PubMed: 5219694]
    245.
    Sypherd P.S. and Strauss N. (1963) The role of RNA in repression of enzyme synthesis. Proceedings of the National Academy of Sciences USA 50: 1059–1066. [PMC free article: PMC221274] [PubMed: 14096178]
    246.
    Goldstein L. (1976) Role for small nuclear RNAs in “programming” chromosomal information? Nature 261: 519–521. [PubMed: 934289]
    247.
    Kanehisa T., Fujitani H., Sano M. and Tanaka T. (1971) Studies on low molecular weight RNA of chromatin. Effects of template activity of chick liver chromatin. Biochimica et Biophysica Acta 240: 46–55. [PubMed: 4940156]
    248.
    Kanehisa T., Tanaka T. and Kano Y. (1972) Low molecular RNA associated with chromatin: Purification and characterization of RNA that stimulates RNA synthesis. Biochimica et Biophysica Acta 277: 584–589. [PubMed: 4560816]
    249.
    Kanehisa T., Oki Y. and Ikuta K. (1974) Partial specificity of low-molecular weight RNA that stimulates RNA synthesis in various tissues. Archives of Biochemistry and Biophysics 165: 146–152. [PubMed: 4374127]
    250.
    Bekhor I. (1973) Physical studies on the effect of chromosomal RNA on reconstituted nucleohistones. Archives of Biochemistry and Biophysics 155: 39–46. [PubMed: 4576362]
    251.
    Paul J. and Duerksen J.D. (1975) Chromatin-associated RNA content of heterochromatin and euchromatin. Molecular and Cellular Biochemistry 9: 9–16. [PubMed: 1186664]
    252.
    Herman R., Weymouth L. and Penman S. (1978) Heterogeneous nuclear RNA-protein fibers in chromatin-depleted nuclei. Journal of Cell Biology 78: 663–674. [PMC free article: PMC2110193] [PubMed: 701354]
    253.
    Pederson T. and Bhorjee J.S. (1979) Evidence for a role of RNA in eukaryotic chromosome structure. Metabolically stable, small nuclear RNA species are covalently linked to chromosomal DNA in HeLa cells. Journal of Molecular Biology 128: 451–480. [PubMed: 571474]
    254.
    Monahan J.J. and Hall R.H. (1973) Fractionation of chromatin components. Canadian Journal of Biochemistry 51: 709–720. [PubMed: 4196342]
    255.
    Marzluff Jr. W.F., White E.L., Benjamin R. and Huang R.C. (1975) Low molecular weight RNA species from chromatin. Biochemistry 14: 3715–3724. [PubMed: 1172446]
    256.
    Monahan J.J. and Hall R.H. (1974) Fractionation of L-cell chromatin into DNA, RNA, and protein fractions on Cs2SO4 equilibruim density gradients. Analytical Biochemistry 62: 217–239. [PubMed: 4473915]
    257.
    Pierpont M.E. and Yunis J.J. (1977) Localization of chromosomal RNA in human G-banded metaphase chromosomes. Experimental Cell Research 106: 303–308. [PubMed: 862667]
    258.
    Bachellerie J.P., Puvion E. and Zalta J.P. (1975) Ultrastructural organization and biochemical characterization of chromatin - RNA - protein complexes isolated from mammalian cell nuclei. European Journal of Biochemistry 58: 327–337. [PubMed: 1102303]
    259.
    Bonner J. (1971) Problematic chromosomal RNA. Nature 231: 543–544. [PubMed: 4933003]
    260.
    von Heyden H.W. and Zachau H.G. (1971) Characterization of RNA in fractions of calf thymus chromatin. Biochimica et Biophysica Acta 232: 651–660. [PubMed: 5556846]
    261.
    Tolstoshev P. and Wells J.R. (1974) Nature and origins of chromatin-associated ribonucleic acid of avian reticulocytes. Biochemistry 13: 103–111. [PubMed: 4586934]
    262.
    Artman M. and Roth J.S. (1971) Chromosomal RNA: An artifact of preparation? Journal of Molecular Biology 60: 291–301. [PubMed: 5099295]
    263.
    Alfageme C.R. and Infante A.A. (1975) Nuclear RNA in sea urchin embryos. II. Absence of “cRNA”. Experimental Cell Research 96: 263–270. [PubMed: 1238285]
    264.
    Pederson T. (2009) The discovery of eukaryotic genome design and its forgotten corollary–the postulate of gene regulation by nuclear RNA. FASEB Journal 23: 2019–2021. [PubMed: 19567373]
    265.
    Getz M.J. and Saunders G.F. (1973) Origins of human leukocyte chromatin-associated RNA. Biochimica et Biophysica Acta 312: 555–573. [PubMed: 4724600]
    266.
    Bynum J.W. and Volkin E. (1980) Chromatin-associated RNA: Differential extraction and characterization. Biochimica et Biophysica Acta 607: 304–318. [PubMed: 7370269]
    267.
    Pederson T. (1977) Isolation and characterization of chromatin from the cellular slime mold, Dictyostelium discoideum. Biochemistry 16: 2771–2777. [PubMed: 560856]
    268.
    Elgin S.C. and Bonner J. (1970) Limited heterogeneity of the major nonhistone chromosomal proteins. Biochemistry 9: 4440–4447. [PubMed: 5472713]
    269.
    Bakke A.C. and Bonner J. (1979) Purification and the histones of Dictyostelium discoideum chromatin. Biochemistry 18: 4556–4562. [PubMed: 497154]
    270.
    Zbarskii I.B. and Debov S.S. (1948) On the proteins of the cell nucleus. Doklady Akademii Nauk SSSR 63: 795–798.
    271.
    Pederson T. (2000) Half a century of “the nuclear matrix”. Molecular Biology of the Cell 11: 799–805. [PMC free article: PMC14811] [PubMed: 10712500]
    272.
    Soyer M.-O. and Haapala O.K. (1974) Structural changes of dinoflagellate chromosomes by pronase and ribonuclease. Chromosoma 47: 179–192. [PubMed: 4477059]
    273.
    Penman S., et al. (1982) Cytoplasmic and nuclear architecture in cells and tissue: Form, functions, and mode of assembly. Cold Spring Harbor Symposia on Quantitative Biology 46: 1013–1028. [PubMed: 6955094]
    274.
    Nickerson J.A., Krochmalnic G., Wan K.M. and Penman S. (1989) Chromatin architecture and nuclear RNA. Proceedings of the National Academy of Sciences USA 86: 177–181. [PMC free article: PMC286427] [PubMed: 2911567]
    275.
    Scherrer K. (1989) A unified matrix hypothesis of DNA-directed morphogenesis, protodynamism and growth control. Bioscience Reports 9: 157–188. [PubMed: 2765661]
    276.
    Scherrer K. (2003) Historical review: The discovery of ‘giant’ RNA and RNA processing: 40 years of enigma. Trends in Biochemical Sciences 28: 566–571. [PubMed: 14559186]
    277.
    Scherrer K. and Darnell J.E. (1962) Sedimentation characteristics of rapidly labelled RNA from HeLa cells. Biochemical and Biophysical Research Communications 7: 486–490. [PubMed: 14498283]
    278.
    Georgiev G.P. and Mantieva V.L. (1962) The isolation of DNA-like RNA and ribosomal RNA from the nucleolo-chromosomal apparatus of mammalian cells. Biochimica et Biophysica Acta 61: 153–154. [PubMed: 13897801]
    279.
    Scherrer K., Darnell J.E. and Latham H. (1963) Demonstration of an unstable RNA and of a precursor to ribosomal RNA in Hela cells. Proceedings of the National Academy of Sciences USA 49: 240–248. [PMC free article: PMC299789] [PubMed: 13991616]
    280.
    Georgiev G.P., Samarina O.P., Lerman M.I., Smirnov M.N. and Severtzov A.N. (1963) Biosynthesis of messenger and ribosomal ribonucleic acids in the nucleolochromosomal apparatus of animal cells. Nature 200: 1291–1294. [PubMed: 14098472]
    281.
    Scherrer K. and Marcaud L. (1968) Messenger RNA in avian erythroblasts at transcriptional and translational levels and problem of regulation in animal cells. Journal of Cellular Physiology 72: 181–212. [PubMed: 5693297]
    282.
    Soeiro R., Birnboim H.C. and Darnell J.E. (1966) Rapidly labeled HeLa cell nuclear RNA. II. Base composition and cellular localization of a heterogeneous RNA fraction. Journal of Molecular Biology 19: 362–372. [PubMed: 5969071]
    283.
    Warner J.R., Soeiro R., Birnboim H.C., Girard M. and Darnell J.E. (1966) Rapidly labeled HeLa cell nuclear RNA. I. Identification by zone sedimentation of a heterogeneous fraction separate from ribosomal precursor RNA. Journal of Molecular Biology 19: 349–361. [PubMed: 5969070]
    284.
    Attardi G., Parnas H., Hwang M.I. and Attardi B. (1966) Giant-size rapidly labeled nuclear ribonucleic acid and cytoplasmic messenger ribonucleic acid in immature duck erythrocytes. Journal of Molecular Biology 20: 145–182. [PubMed: 5970657]
    285.
    Penman S., Smith I. and Holtzman E. (1966) Ribosomal RNA synthesis and processing in a particulate site in the HeLa cell nucleus. Science 154: 786–789. [PubMed: 5919449]
    286.
    Penman S. (1966) RNA metabolism in the HeLa cell nucleus. Journal of Molecular Biology 17: 117–130. [PubMed: 5961144]
    287.
    Weinberg R.A., Loening U., Willems M. and Penman S. (1967) Acrylamide gel electrophoresis of HeLa cell nucleolar RNA. Proceedings of the National Academy of Sciences USA 58: 1088–1095. [PMC free article: PMC335751] [PubMed: 5233837]
    288.
    Scherrer K., Marcaud L., Zajdela F., London I.M. and Gros F. (1966) Patterns of RNA metabolism in a differentiated cell: A rapidly labeled, unstable 60S RNA with messenger properties in duck erythroblasts. Proceedings of the National Academy of Sciences USA 56: 1571–1578. [PMC free article: PMC220034] [PubMed: 5230317]
    289.
    Houssais J.F. and Attardi G. (1966) High Molecular weight nonribosomal-type nuclear RNA and cytoplasmic messenger RNA in Hela cells. Proceedings of the National Academy of Sciences USA 56: 616–623. [PMC free article: PMC224417] [PubMed: 5229981]
    290.
    Bryson V. and Vogel H.J. (1965) Evolving genes and proteins. Science 147: 68–71. [PubMed: 17799782]
    291.
    Harris H. (2013) History: Non-coding RNA foreseen 48 years ago. Nature 497: 188. [PubMed: 23657339]
    292.
    Penman S., Vesco C. and Penman M. (1968) Localization and kinetics of formation of nuclear heterodisperse RNA, cytoplasmic heterodisperse RNA and polyribosome-associated messenger RNA in HeLa cells. Journal of Molecular Biology 34: 49–60. [PubMed: 4106524]
    293.
    Penman S., Rosbash M. and Penman M. (1970) Messenger and heterogeneous nuclear RNA in HeLa cells: Differential inhibition by cordycepin. Proceedings of the National Academy of Sciences USA 67: 1878–1885. [PMC free article: PMC283442] [PubMed: 5275385]
    294.
    Lengyel J. and Penman S. (1975) hnRNA size and processing as related to different DNA content in two dipterans: Drosophila and Aedes. Cell 5: 281–290. [PubMed: 807333]
    295.
    Allfrey V.G. and Mirsky A.E. (1962) Evidence for complete DNA-dependence of RNA synthesis in isolated thymus nuclei. Proceedings of the National Academy of Sciences USA 48: 1590–1596. [PMC free article: PMC221004] [PubMed: 13860598]
    296.
    Shearer R.W. and McCarthy B.J. (1967) Evidence for ribonucleic acid molecules restricted to the cell nucleus. Biochemistry 6: 283–289. [PubMed: 6030325]
    297.
    Bantle J.A. and Hahn W.E. (1976) Complexity and characterization of polyadenylated RNA in the mouse brain. Cell 8: 139–150. [PubMed: 986249]
    298.
    Levy B., Johnson C.B. and McCarthy B.J. (1976) Diversity of sequences in total and polyadenylated nuclear RNA from Drosophila cells. Nucleic Acids Research 3: 1777–1789. [PMC free article: PMC343036] [PubMed: 967676]
    299.
    Lewis E.B. (1963) Genes and developmental pathways. American Zoologist 3: 33–56.
    300.
    Jacob F. and Monod J. (1961) Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology 3: 318–356. [PubMed: 13718526]
    301.
    Mayr E. (1961) Cause and effect in biology. Science 134: 1501–1506. [PubMed: 14471768]
    302.
    Kauffman S. (1974) The large scale structure and dynamics of gene control circuits: An ensemble approach. Journal of Theoretical Biology 44: 167–190. [PubMed: 4595774]
    303.
    Kauffman S. (1969) Homeostasis and differentiation in random genetic control networks. Nature 224: 177–178. [PubMed: 5343519]
    304.
    Georgiev G.P. (1969) On the structural organization of operon and the regulation of RNA synthesis in animal cells. Journal of Theoretical Biology 25: 473–490. [PubMed: 5387051]
    305.
    Britten R.J. and Kohne D.E. (1968) Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science 161: 529–540. [PubMed: 4874239]
    306.
    Darnell J.E. (2002) The surprises of mammalian molecular cell biology. Nature Medicine 8: 1068–1071. [PubMed: 12357235]
    307.
    Sarkar N. (1997) Polyadenylation of mRNA in prokaryotes. Annual Review of Biochemistry 66: 173–197. [PubMed: 9242905]
    308.
    Singer R.H. and Penman S. (1972) Stability of HeLa cell mRNA in actinomycin. Nature 240: 100–102. [PubMed: 4118029]
    309.
    Carninci P., et al. (1996) High-efficiency full-length cDNA cloning by biotinylated CAP trapper. Genomics 37: 327–336. [PubMed: 8938445]
    310.
    Milcarek C., Price R. and Penman S. (1974) The metabolism of a poly(A) minus mRNA fraction in HeLa cells. Cell 3: 1–10. [PubMed: 4213457]
    311.
    Katinakis P.K., Slater A. and Burdon R.H. (1980) Non-polyadenylated mRNAs from eukaryotes. FEBS Letters 116: 1–7. [PubMed: 6997068]
    312.
    Salditt-Georgieff M., Harpold M.M., Wilson M.C. and Darnell Jr. J.E. (1981) Large heterogeneous nuclear ribonucleic acid has three times as many 5′ caps as polyadenylic acid segments, and most caps do not enter polyribosomes. Molecular Cell Biology 1: 179–187. [PMC free article: PMC369657] [PubMed: 6152852]
    313.
    Cheng J., et al. (2005) Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308: 1149–1154. [PubMed: 15790807]
    314.
    Lee S.Y., Mendecki J. and Brawerman G. (1971) A polynucleotide segment rich in adenylic acid in the rapidly-labeled polyribosomal RNA component of mouse sarcoma 180 ascites cells. Proceedings of the National Academy of Sciences USA 68: 1331–1335. [PMC free article: PMC389183] [PubMed: 5288382]
    315.
    Darnell J.E., Wall R. and Tushinski R.J. (1971) An adenylic acid-rich sequence in messenger RNA of HeLa cells and its possible relationship to reiterated sites in DNA. Proceedings of the National Academy of Sciences USA 68: 1321–1325. [PMC free article: PMC389181] [PubMed: 5288381]
    316.
    Edmonds M., Vaughan Jr. M.H., and Nakazato H. (1971) Polyadenylic acid sequences in the heterogeneous nuclear RNA and rapidly-labeled polyribosomal RNA of HeLa cells: Possible evidence for a precursor relationship. Proceedings of the National Academy of Sciences USA 68: 1336–1340. [PMC free article: PMC389184] [PubMed: 5288383]
    317.
    Perry R.P., Bard E., Hames B.D., Kelly D.E. and Schibler U. (1976) The relationship between hnRNA and mRNA. Progress in Nucleic Acid Research and Molecular Biology 19: 275–292. [PubMed: 1019347]
    318.
    Salditt-Georgieff M., et al. (1976) Methyl labeling of HeLa cell hnRNA: A comparison with mRNA. Cell 7: 227–237. [PubMed: 954080]
    319.
    Bachenheimer S. and Darnell J.E. (1975) Adenovirus-2 mRNA is transcribed as part of a high-molecular-weight precursor RNA. Proceedings of the National Academy of Sciences USA 72: 4445–4449. [PMC free article: PMC388738] [PubMed: 1060124]
    320.
    Weber J., Jelinek W. and Darnell J.E. (1977) The definition of a large viral transcription unit late in Ad2 infection of HeLa cells: Mapping of nascent RNA molecular labeled in isolated nuclei. Cell 10: 611–616. [PubMed: 862022]
    321.
    Nevins J.R. and Darnell J.E. (1978) Groups of adenovirus type 2 mRNAs derived from a large primary transcript: Probable nuclear origin and possible common 3′ ends. Journal of Virology 25: 811–823. [PMC free article: PMC525975] [PubMed: 642075]
    322.
    Ramanathan A., Robb G.B. and Chan S.-H. (2016) mRNA capping: Biological functions and applications. Nucleic Acids Research 44: 7511–7526. [PMC free article: PMC5027499] [PubMed: 27317694]
    323.
    Wang J., et al. (2019) Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA. Nucleic Acids Research 47: e130. [PMC free article: PMC6847653] [PubMed: 31504804]
    324.
    Miura K.-I., Watanabe K. and Sugiura M. (1974) 5′-Terminal nucleotide sequences of the double-stranded RNA of silkworm cytoplasmic polyhedrosis virus. Journal of Molecular Biology 86: 31–48. [PubMed: 4369455]
    325.
    Miura K.-I., Watanabe K., Sugiura M. and Shatkin A.J. (1974) The 5′-terminal nucleotide sequences of the double-stranded RNA of human reovirus. Proceedings of the National Academy of Sciences USA 71: 3979–3983. [PMC free article: PMC434310] [PubMed: 4530278]
    326.
    Desrosiers R., Friderici K. and Rottman F. (1974) Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proceedings of the National Academy of Sciences USA 71: 3971–3975. [PMC free article: PMC434308] [PubMed: 4372599]
    327.
    Furuichi Y., et al. (1975) Methylated, blocked 5 termini in HeLa cell mRNA. Proceedings of the National Academy of Sciences USA 72: 1904–1908. [PMC free article: PMC432656] [PubMed: 1057180]
    328.
    Furuichi Y. and Miura K.-I. (1975) A blocked structure at the 5′ terminus of mRNA from cytoplasmic polyhedrosis virus. Nature 253: 374–375. [PubMed: 163011]
    329.
    Furuichi Y. (2015) Discovery of m7G-cap in eukaryotic mRNAs. Proceedings of the Japan Academy, Series B 91: 394–409. [PMC free article: PMC4729855] [PubMed: 26460318]
    330.
    Konarska M.M., Padgett R.A. and Sharp P.A. (1984) Recognition of cap structure in splicing in vitro of mRNA precursors. Cell 38: 731–736. [PubMed: 6567484]
    331.
    Fechter P. and Brownlee G.G. (2005) Recognition of mRNA cap structures by viral and cellular proteins. Journal of General Virology 86: 1239–1249. [PubMed: 15831934]
    332.
    Adams J.M. and Cory S. (1975) Modified nucleosides and bizarre 5′-termini in mouse myeloma mRNA. Nature 255: 28–33. [PubMed: 1128665]
    333.
    Shatkin A. (1976) Capping of eucaryotic mRNAs. Cell 9: 645–653. [PubMed: 1017010]
    334.
    Banerjee A.K. (1980) 5′-terminal cap structure in eucaryotic messenger ribonucleic acids. Microbiological Reviews 44: 175–205. [PMC free article: PMC373176] [PubMed: 6247631]
    335.
    Perry R. and Kelley D. (1974) Existence of methylated messenger RNA in mouse L cells. Cell 1: 37–42.

    Chapter 5

    1.
    Atkin N.B., Mattinson G., Becak W. and Ohno S. (1965) The comparative DNA content of 19 species of placental mammals, reptiles and birds. Chromosoma 17: 1–10. [PubMed: 5833947]
    2.
    Cui J., Schlub T.E. and Holmes E.C. (2014) An allometric relationship between the genome length and virion volume of viruses. Journal of Virology 88: 6403–6410. [PMC free article: PMC4093846] [PubMed: 24672040]
    3.
    Campillo-Balderas J.A., Lazcano A. and Becerra A. (2015) Viral genome size distribution does not correlate with the antiquity of the host lineages. Frontiers in Ecology and Evolution 3: 143.
    4.
    Mohanta T.K. and Bae H. (2015) The diversity of fungal genome. Biological Procedures Online 17: 8. [PMC free article: PMC4392786] [PubMed: 25866485]
    5.
    Corradi N., Pombert J.-F., Farinelli L., Didier E.S. and Keeling P.J. (2010) The complete sequence of the smallest known nuclear genome from the microsporidian Encephalitozoon intestinalis. Nature Communications 1: 77. [PMC free article: PMC4355639] [PubMed: 20865802]
    6.
    Pedersen R.A. (1971) DNA content, ribosomal gene multiplicity, and cell size in fish. Journal of Experimental Zoology 177: 65–78. [PubMed: 5569239]
    7.
    Pellicer J., Fay M.F. and Leitch I.J. (2010) The largest eukaryotic genome of them all? Botanical Journal of the Linnean Society 164: 10–15.
    8.
    Elliott T.A. and Gregory T.R. (2015) What’s in a genome? The C-value enigma and the evolution of eukaryotic genome content. Philosophical Transactions of the Royal Society B: Biological Sciences 370: 20140331. [PMC free article: PMC4571570] [PubMed: 26323762]
    9.
    Ahn A.H. and Kunkel L.M. (1993) The structural and functional diversity of dystrophin. Nature Genetics 3: 283–291. [PubMed: 7981747]
    10.
    Pozzoli U., et al. (2003) Comparative analysis of vertebrate dystrophin loci indicate intron gigantism as a common feature. Genome Research 13: 764–772. [PMC free article: PMC430921] [PubMed: 12727896]
    11.
    Nakabayashi K. and Scherer S.W. (2001) The human contactin-associated protein-like 2 gene (CNTNAP2) spans over 2 Mb of DNA at chromosome 7q35. Genomics 73: 108–112. [PubMed: 11352571]
    12.
    Vogel F. (1964) A preliminary estimate of the number of human genes. Nature 201: 847. [PubMed: 14161239]
    13.
    Watson J.D. (1965) Molecular Biology of the Gene (Benjamin, New York).
    14.
    Kauffman S.A. (1969) Metabolic stability and epigenesis in randomly constructed genetic nets. Journal of Theoretical Biology 22: 437–467. [PubMed: 5803332]
    15.
    Britten R.J. and Davidson E.H. (1969) Gene regulation for higher cells: A theory. Science 165: 349–357. [PubMed: 5789433]
    16.
    Waring M. and Britten R.J. (1966) Nucleotide sequence repetition: A rapidly reassociating fraction of mouse DNA. Science 154: 791–794. [PubMed: 5919450]
    17.
    Britten R.J. and Kohne D.E. (1968) Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science 161: 529–540. [PubMed: 4874239]
    18.
    Scheller R.H., Costantini F.D., Kozlowski M.R., Britten R.J. and Davidson E.H. (1978) Specific representation of cloned repetitive DNA sequences in sea urchin RNAs. Cell 15: 189–203. [PubMed: 699041]
    19.
    Jurka J., Kapitonov V.V., Kohany O. and Jurka M.V. (2007) Repetitive sequences in complex genomes: Structure and evolution. Annual Review of Genomics and Human Genetics 8: 241–259. [PubMed: 17506661]
    20.
    Cuny G., Soriano P., Macaya G. and Bernardi G. (1981) The major components of the mouse and human genomes. 1. Preparation, basic properties and compositional heterogeneity. European Journal of Biochemistry 115: 227–233. [PubMed: 7238506]
    21.
    Bernardi G., et al. (1985) The mosaic genome of warm-blooded vertebrates. Science 228: 953–958. [PubMed: 4001930]
    22.
    Wells J.N. and Feschotte C. (2020) A field guide to eukaryotic transposable elements. Annual Review of Genetics 54: 539–561. [PMC free article: PMC8293684] [PubMed: 32955944]
    23.
    McClintock B. (1934) The relationship of a particular chromosomal element to the development of the nucleoli in Zea mays. Zeitschrift für Zellforschung und mikroskopische Anatomie 21: 294–328.
    24.
    McStay B. (2016) Nucleolar organizer regions: Genomic ‘dark matter’ requiring illumination. Genes & Development 30: 1598–1610. [PMC free article: PMC4973289] [PubMed: 27474438]
    25.
    McClintock B. (1951) Chromosome organization and genic expression. Cold Spring Harbor Symposia on Quantitative Biology 16: 13–47. [PubMed: 14942727]
    26.
    McClintock B. (1956) Controlling elements and the gene. Cold Spring Harbor Symposia on Quantitative Biology 21: 197–216. [PubMed: 13433592]
    27.
    McClintock B. (1961) Some parallels between gene control systems in maize and in bacteria. American Naturalist 95: 265–277.
    28.
    McClintock B. (1938) The production of homozygous deficient tissues with mutant characteristics by means of the aberrant mitotic behavior of ring-shaped chromosomes. Genetics 23: 315–376. [PMC free article: PMC1209016] [PubMed: 17246891]
    29.
    McClintock B. (1941) The stability of broken ends of chromosomes in Zea mays. Genetics 26: 234–282. [PMC free article: PMC1209127] [PubMed: 17247004]
    30.
    Creighton H.B. and McClintock B. (1931) A correlation of cytological and genetical crossing-over in Zea mays. Proceedings of the National Academy of Sciences USA 17: 492–497. [PMC free article: PMC1076098] [PubMed: 16587654]
    31.
    Fedoroff N.V. (2012) McClintock’s challenge in the 21st century. Proceedings of the National Academy of Sciences USA 109: 20200–20203. [PMC free article: PMC3528499] [PubMed: 23150590]
    32.
    Chomet P. and Martienssen R. (2017) Barbara McClintock’s final years as nobelist and mentor: A memoir. Cell 170: 1049–1054. [PubMed: 28886375]
    33.
    McClintock B. (1950) The origin and behavior of mutable loci in maize. Proceedings of the National Academy of Sciences USA 36: 344–355. [PMC free article: PMC1063197] [PubMed: 15430309]
    34.
    Ravindran S. (2012) Barbara McClintock and the discovery of jumping genes. Proceedings of the National Academy of Sciences USA 109: 20198–20199. [PMC free article: PMC3528533] [PubMed: 23236127]
    35.
    Witkin E.M. (2002) Chances and choices: Cold Spring Harbor 1944–1955. Annual Review of Microbiology 56: 1–15. [PubMed: 12142497]
    36.
    Brink R.A. and Nilan R.A. (1952) The relation between light variegated and medium variegated pericarp in maize. Genetics 37: 519–544. [PMC free article: PMC1209573] [PubMed: 17247408]
    37.
    Bennett E.A., et al. (2008) Active Alu retrotransposons in the human genome. Genome Research 18: 1875–1883. [PMC free article: PMC2593586] [PubMed: 18836035]
    38.
    Houck C.M., Rinehart F.P. and Schmid C.W. (1979) A ubiquitous family of repeated DNA sequences in the human genome. Journal of Molecular Biology 132: 289–306. [PubMed: 533893]
    39.
    Fedoroff N.V. (1989) About maize transposable elements and development. Cell 56: 181–191. [PubMed: 2536297]
    40.
    Bai L. and Brutnell T.P. (2011) The activator/dissociation transposable elements comprise a two-component gene regulatory switch that controls endogenous gene expression in maize. Genetics 187: 749–759. [PMC free article: PMC3063669] [PubMed: 21196519]
    41.
    Fedoroff N.V. (1999) The Suppressor-mutator element and the evolutionary riddle of transposons. Genes to Cells 4: 11–19. [PubMed: 10231389]
    42.
    Jones R.N. (2005) McClintock’s controlling elements: The full story. Cytogenetic and Genome Research 109: 90–103. [PubMed: 15753564]
    43.
    Fedoroff N., Wessler S. and Shure M. (1983) Isolation of the transposable maize controlling elements Ac and Ds. Cell 35: 235–242. [PubMed: 6313225]
    44.
    Green M.M. (1977) Genetic instability in Drosophila melanogaster: De novo induction of putative insertion mutations. Proceedings of the National Academy of Sciences USA 74: 3490–3493. [PMC free article: PMC431616] [PubMed: 16592430]
    45.
    Green M.M. (1986) Genetic instability in Drosophila melanogaster: The genetics of an MR element that makes complete P insertion mutations. Proceedings of the National Academy of Sciences USA 83: 1036–1040. [PMC free article: PMC323005] [PubMed: 3006025]
    46.
    Mérel V., Boulesteix M., Fablet M. and Vieira C. (2020) Transposable elements in Drosophila. Mobile DNA 11: 23. [PMC free article: PMC7334843] [PubMed: 32636946]
    47.
    Shapiro J.A. (1969) Mutations caused by the insertion of genetic material into the galactose operon of Escherichia coli. Journal of Molecular Biology 40: 93–105. [PubMed: 4903362]
    48.
    Kleckner N. (1981) Transposable elements in prokaryotes. Annual Review of Genetics 15: 341–404. [PubMed: 6279020]
    49.
    Engels W.R. and Preston C.R. (1981) Identifying P factors in Drosophila by means of chromosome breakage hotspots. Cell 26: 421–428. [PubMed: 6276017]
    50.
    Ryder E. and Russell S. (2003) Transposable elements as tools for genomics and genetics in Drosophila. Briefings in Functional Genomics and Proteomics 2: 57–71. [PubMed: 15239944]
    51.
    Comfort N.C. (2003) The Tangled Field: Barbara McClintock’s Search for the Patterns of Genetic Control (Harvard University Press, New York).
    52.
    McClintock B. (1965) Components of action of the regulators Spm and Ac. Carnegie Institution of Washington Year Book 64: 527–1526.
    53.
    McClintock B. (1966) Regulation of pattern of gene expression by controlling elements in maize. Carnegie Institution of Washington Yearbook 65: 568–577.
    54.
    McClintock B. (1958) The suppressor-mutator system of control of gene action in maize. Carnegie Institution of Washington Year Book 57: 415–429.
    55.
    McClintock B. (1953) Induction of instability at selected loci in maize. Genetics 38: 579–599. [PMC free article: PMC1209627] [PubMed: 17247459]
    56.
    Martienssen R., Barkan A., Taylor W.C. and Freeling M. (1990) Somatically heritable switches in the DNA modification of Mu transposable elements monitored with a suppressible mutant in maize. Genes & Development 4: 331–343. [PubMed: 2159936]
    57.
    Volpe T.A. et al. (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297: 1833–1837. [PubMed: 12193640]
    58.
    Lippman Z. et al. (2004) Role of transposable elements in heterochromatin and epigenetic control. Nature 430: 471–476. [PubMed: 15269773]
    59.
    Lippman Z. and Martienssen R. (2004) The role of RNA interference in heterochromatic silencing. Nature 431: 364–370. [PubMed: 15372044]
    60.
    Slotkin R.K. and Martienssen R. (2007) Transposable elements and the epigenetic regulation of the genome. Nature Reviews Genetics 8: 272–285. [PubMed: 17363976]
    61.
    McClintock B. (1984) The significance of responses of the genome to challenge. Science 226: 792–801. [PubMed: 15739260]
    62.
    Bateson W. and Pellew C. (1915) On the genetics of “Rogues” among culinary peas (Pisum sativum). Journal of Genetics 5: 13–36.
    63.
    Bateson W. and Pellew C. (1920) The genetics of “rogues” among culinary peas (i). Proceedings of The Royal Society B: Biological Sciences 91: 186–195.
    64.
    Brink R.A. (1956) A genetic change associated with the R locus in maize which is directed and potentially reversible. Genetics 41: 872–889. [PMC free article: PMC1224369] [PubMed: 17247669]
    65.
    Brink R.A. (1958) Paramutation at the R locus in maize. Cold Spring Harbor Symposia on Quantitative Biology 23: 379–391. [PubMed: 13635569]
    66.
    Chandler V.L. (2007) Paramutation: From maize to mice. Cell 128: 641–645. [PubMed: 17320501]
    67.
    Pilu R. (2015) Paramutation phenomena in plants. Seminars in Cell & Developmental Biology 44: 2–10. [PubMed: 26335267]
    68.
    Hollick J.B. (2017) Paramutation and related phenomena in diverse species. Nature Reviews Genetics 18: 5–23. [PubMed: 27748375]
    69.
    Slack J.M.W. (2002) Conrad Hal Waddington: The last Renaissance biologist? Nature Reviews Genetics 3: 889–895. [PubMed: 12415319]
    70.
    Waddington C.H. (1956) Genetic assimilation of the bithorax phenotype. Evolution 10: 1–13.
    71.
    Waddington C.H. (1953) Genetic assimilation of an acquired character. Evolution 7: 118–126.
    72.
    Bard J.B.L. (2017) C.H. Waddington’s differences with the creators of the modern evolutionary synthesis: A tale of two genes. History and Philosophy of the Life Sciences 39: 18. [PMC free article: PMC5548827] [PubMed: 28791592]
    73.
    Banta J.A. and Richards C.L. (2018) Quantitative epigenetics and evolution. Heredity 121: 210–224. [PMC free article: PMC6082842] [PubMed: 29980793]
    74.
    Nishikawa K. and Kinjo A.R. (2018) Mechanism of evolution by genetic assimilation: Equivalence and independence of genetic mutation and epigenetic modulation in phenotypic expression. Biophysical Reviews 10: 667–676. [PMC free article: PMC5899745] [PubMed: 29468522]
    75.
    Fanti L., Piacentini L., Cappucci U., Casale A.M. and Pimpinelli S. (2017) Canalization by selection of de novo induced mutations. Genetics 206: 1995–2006. [PMC free article: PMC5560803] [PubMed: 28576865]
    76.
    Vigne P., et al. (2021) A single-nucleotide change underlies the genetic assimilation of a plastic trait. Science Advances 7: eabd9941. [PMC free article: PMC7857674] [PubMed: 33536214]
    77.
    Beddington R.S.P., Rashbass P. and Wilson V. (1992) Brachyury - a gene affecting mouse gastrulation and early organogenesis. Development 116: 157–165. [PubMed: 1299362]
    78.
    Johnson D.R. (1974) Hairpin-tail: A case of post-reductional gene action in the mouse egg? Genetics 76: 795–805. [PMC free article: PMC1213105] [PubMed: 4838760]
    79.
    Lyon M.F. and Glenister P.H. (1977) Factors affecting the observed number of young resulting from adjacent-2 disjunction in mice carrying a translocation. Genetical Research 29: 83–92. [PubMed: 559611]
    80.
    Surani M.A.H., Barton S.C. and Norris M.L. (1984) Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308: 548–550. [PubMed: 6709062]
    81.
    McGrath J. and Solter D. (1984) Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37: 179–183. [PubMed: 6722870]
    82.
    Barton S.C., Surani M.A.H. and Norris M.L. (1984) Role of paternal and maternal genomes in mouse development. Nature 311: 374–376. [PubMed: 6482961]
    83.
    Ferguson-Smith A.C. and Bourc’his D. (2018) The discovery and importance of genomic imprinting. eLife 7: e42368. [PMC free article: PMC6197852] [PubMed: 30343680]
    84.
    Reik W. and Walter J. (2001) Evolution of imprinting mechanisms: The battle of the sexes begins in the zygote. Nature Genetics 27: 255–256. [PubMed: 11242103]
    85.
    Reik W. and Lewis A. (2005) Co-evolution of X-chromosome inactivation and imprinting in mammals. Nature Reviews Genetics 6: 403–410. [PubMed: 15818385]
    86.
    Renfree M.B., Suzuki S. and Kaneko-Ishino T. (2013) The origin and evolution of genomic imprinting and viviparity in mammals. Philosophical Transactions of the Royal Society B: Biological Sciences 368: 20120151. [PMC free article: PMC3539366] [PubMed: 23166401]
    87.
    Patten M.M., et al. (2014) The evolution of genomic imprinting: Theories, predictions and empirical tests. Heredity 113: 119–128. [PMC free article: PMC4105453] [PubMed: 24755983]
    88.
    Morison I.M., Ramsay J.P. and Spencer H.G. (2005) A census of mammalian imprinting. Trends in Genetics 21: 457–465. [PubMed: 15990197]
    89.
    Koerner M.V., Pauler F.M., Huang R. and Barlow D.P. (2009) The function of non-coding RNAs in genomic imprinting. Development 136: 1771–1783. [PMC free article: PMC2847617] [PubMed: 19429783]
    90.
    Bogutz A.B., et al. (2019) Evolution of imprinting via lineage-specific insertion of retroviral promoters. Nature Communications 10: 5674. [PMC free article: PMC6908575] [PubMed: 31831741]
    91.
    Greally J.M. (2002) Short interspersed transposable elements (SINEs) are excluded from imprinted regions in the human genome. Proceedings of the National Academy of Sciences USA 99: 327–332. [PMC free article: PMC117560] [PubMed: 11756672]
    92.
    Renfree M.B., Papenfuss A.T., Shaw G. and Pask A.J. (2009) Eggs, embryos and the evolution of imprinting: Insights from the platypus genome. Reproduction, Fertility and Development 21: 935–942. [PubMed: 19874717]
    93.
    Vogels A. and Fryns J.P. (2002) The Prader-Willi syndrome and the Angelman syndrome. Genetic Counseling 13: 385–396. [PubMed: 12558108]
    94.
    Eggermann T., et al. (2015) Imprinting disorders: A group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci. Clinical Epigenetics 7: 123. [PMC free article: PMC4650860] [PubMed: 26583054]
    95.
    Butler M.G. (2020) Imprinting disorders in humans: A review. Current Opinion in Pediatrics 32: 719–729. [PMC free article: PMC8791075] [PubMed: 33148967]
    96.
    Cockett N.E., et al. (1996) Polar overdominance at the ovine callipyge locus. Science 273: 236–238. [PubMed: 8662506]
    97.
    Charlier C., et al. (2001) The callipyge mutation enhances the expression of coregulated imprinted genes in cis without affecting their imprinting status. Nature Genetics 27: 367–369. [PubMed: 11279514]
    98.
    Georges M., Charlier C. and Cockett N. (2003) The callipyge locus: Evidence for the trans interaction of reciprocally imprinted genes. Trends in Genetics 19: 248–252. [PubMed: 12711215]
    99.
    Royo H. and Cavaille J. (2008) Non-coding RNAs in imprinted gene clusters. Biology of the Cell 100: 149–166. [PubMed: 18271756]
    100.
    Meyer P. and Saedler H. (1996) Homology-dependent gene silencing in plants. Annual Review of Plant Physiology and Plant Molecular Biology 47: 23–48. [PubMed: 15012281]
    101.
    Bingham P.M. (1997) Cosuppression comes to the animals. Cell 90: 385–387. [PubMed: 9267017]
    102.
    Garrick D., Fiering S., Martin D.I.K. and Whitelaw E. (1998) Repeat-induced gene silencing in mammals. Nature Genetics 18: 56–59. [PubMed: 9425901]
    103.
    Selker E.U. (2002) Repeat-Induced gene silencing in fungi. Advances in Genetics 46: 439–450. [PubMed: 11931234]
    104.
    Fulci V. and Macino G. (2007) Quelling: Post-transcriptional gene silencing guided by small RNAs in Neurospora crassa. Current Opinion in Microbiology 10: 199–203. [PubMed: 17395524]
    105.
    Matzke M.A. and Mosher R.A. (2014) RNA-directed DNA methylation: An epigenetic pathway of increasing complexity. Nature Reviews Genetics 15: 394–408. [PubMed: 24805120]
    106.
    Ashe H.L., Monks J., Wijgerde M., Fraser P. and Proudfoot N.J. (1997) Intergenic transcription and transinduction of the human beta-globin locus. Genes & Development 11: 2494–2509. [PMC free article: PMC316561] [PubMed: 9334315]
    107.
    Bridges C.B. and Morgan T.H. (1923) The Third-Chromosome Group of Mutant Characters of Drosophila Melanogaster (Carnegie Institution of Washington, New York).
    108.
    Lewis E.B. (1963) Genes and developmental pathways. American Zoologist 3: 33–56.
    109.
    Lewis E.B. (2007) Genes, Development and Cancer, The Life and Work of Edward B. Lewis (Springer, New York).
    110.
    Bateson W. (1894) Materials for the Study of Variation Treated with Especial Regard to Discontinuity in the Origin of Species (Macmillan, New York).
    111.
    Lewis E.B. (1994) Homeosis: The first 100 years. Trends in Genetics 10: 341–343. [PubMed: 7985234]
    112.
    Crow J.F. and Bender W. (2004) Edward B. Lewis, 1918–2004. Genetics 168: 1773–1783. [PMC free article: PMC1448758] [PubMed: 15611154]
    113.
    Lewis E.B. (1978) A gene complex controlling segmentation in Drosophila. Nature 276: 565–570. [PubMed: 103000]
    114.
    Lewis E.B. (1985) Regulation of the genes of the bithorax complex in Drosophila. Cold Spring Harbor Symposia on Quantitative Biology 50: 155–164. [PubMed: 3868476]
    115.
    Peifer M., Karch F. and Bender W. (1987) The bithorax complex: Control of segmental identity. Genes & Development 1: 891–898. [PubMed: 30184830]
    116.
    Duncan I. (1987) The bithorax complex. Annual Review of Genetics 21: 285–319. [PubMed: 3327467]
    117.
    Lewis E.B. (1998) The bithorax complex: The first fifty years. International Journal of Developmental Biology 42: 403–415. [PubMed: 9654025]
    118.
    Maeda R.K. and Karch F. (2006) The ABC of the BX-C: The bithorax complex explained. Development 133: 1413–1422. [PubMed: 16556913]
    119.
    Maeda R.K. and Karch F. (2009) The bithorax complex of Drosophila: An exceptional Hox cluster. Current Topics in Developmental Biology 88: 1–33. [PubMed: 19651300]
    120.
    Akbari O.S., Bousum A., Bae E. and Drewell R.A. (2006) Unraveling cis-regulatory mechanisms at the abdominal-A and Abdominal-B genes in the Drosophila bithorax complex. Developmental Biology 293: 294–304. [PubMed: 16545794]
    121.
    Akam M. (1989) Hox and HOM: Homologous gene clusters in insects and vertebrates. Cell 57: 347–349. [PubMed: 2566382]
    122.
    Lewis E.B. (1955) Some aspects of position pseudoallelism. American Naturalist 89: 73–89.
    123.
    Ingham P. (1985) Abdominal gene organization. Nature 313: 98–99. [PubMed: 3917558]
    124.
    Lewis E.B. (1951) Pseudoallelism and gene evolution. Cold Spring Harbor Symposia on Quantitative Biology 16: 159–174. [PubMed: 14942737]
    125.
    Lewis E.B. (1954) The theory and application of a new method of detecting chromosomal rearrangements in Drosophila melanogaster. American Naturalist 88: 225–239.
    126.
    Zhou J., Ashe H., Burks C. and Levine M. (1999) Characterization of the transvection mediating region of the abdominal-B locus in Drosophila. Development 126: 3057–3065. [PubMed: 10375498]
    127.
    Duncan IW (2002) Transvection effects in Drosophila. Annual Review of Genetics 36: 521–556. [PubMed: 12429702]
    128.
    Galouzis C.C. and Prud’homme B. (2021) Transvection regulates the sex-biased expression of a fly X-linked gene. Science 371: 396–400. [PubMed: 33479152]
    129.
    Hopmann R., Duncan D. and Duncan I. (1995) Transvection in the iab-5,6,7 region of the bithorax complex of Drosophila: Homology independent interactions in trans. Genetics 139: 815–833. [PMC free article: PMC1206383] [PubMed: 7713434]
    130.
    Muller M., Hagstrom K., Gyurkovics H., Pirrotta V. and Schedl P. (1999) The mcp element from the Drosophila melanogaster bithorax complex mediates long-distance regulatory interactions. Genetics 153: 1333–1356. [PMC free article: PMC1460818] [PubMed: 10545463]
    131.
    Gemkow M.J., Verveer P.J. and Arndt-Jovin D.J. (1998) Homologous association of the Bithorax-Complex during embryogenesis: Consequences for transvection in Drosophila melanogaster. Development 125: 4541–4552. [PubMed: 9778512]
    132.
    Duncan I. and Montgomery G. (2002) E. B. Lewis and the bithorax complex: Part II. From cis-trans test to the genetic control of development. Genetics 161: 1–10. [PMC free article: PMC1462105] [PubMed: 12019218]
    133.
    Lewis E.B. (1964) Genetic control and regulation of developmental pathways, in M. Locke (ed.) The Role of Chromosomes in Development (Academic Press, New York).
    134.
    Lawrence P.A. (1992) The Making of a Fly: The Genetics of Animal Design (Blackwell Scientific, New York).
    135.
    Akam M.E., Martinez-Arias A., Weinzierl R. and Wilde C.D. (1985) Function and expression of ultrabithorax in the Drosophila embryo. Cold Spring Harbor Symposia on Quantitative Biology 50: 195–200. [PubMed: 3868478]
    136.
    Hogness D.S., et al. (1985) Regulation and products of the Ubx domain of the bithorax complex. Cold Spring Harbor Symposia on Quantitative Biology 50: 181–194. [PubMed: 3938361]
    137.
    Lipshitz H.D., Peattie D.A. and Hogness D.S. (1987) Novel transcripts from the Ultrabithorax domain of the bithorax complex. Genes & Development 1: 307–322. [PubMed: 3119423]
    138.
    Irish V.F., Martinez-Arias A. and Akam M. (1989) Spatial regulation of the Antennapedia and Ultrabithorax homeotic genes during Drosophila early development. EMBO Journal 8: 1527–1537. [PMC free article: PMC400984] [PubMed: 2569971]
    139.
    Tillib S., et al. (1999) Trithorax- and Polycomb-group response elements within an Ultrabithorax transcription maintenance unit consist of closely situated but separable sequences. Molecular and Cellular Biology 19: 5189–5202. [PMC free article: PMC84362] [PubMed: 10373568]
    140.
    Sanchez-Herrero E. and Akam M. (1989) Spatially ordered transcription of regulatory DNA in the bithorax complex of Drosophila. Development 107: 321–329. [PubMed: 2632227]
    141.
    Bae E., Calhoun V.C., Levine M., Lewis E.B. and Drewell R.A. (2002) Characterization of the intergenic RNA profile at abdominal-A and Abdominal-B in the Drosophila bithorax complex. Proceedings of the National Academy of Sciences USA 99: 16847–16852. [PMC free article: PMC139232] [PubMed: 12481037]
    142.
    Graveley B.R. et al. (2011) The developmental transcriptome of Drosophila melanogaster. Nature 471: 473–479. [PMC free article: PMC3075879] [PubMed: 21179090]
    143.
    Micol J.L. and García-Bellido A. (1988) Genetic analysis of “transvection effects” involving contrabithorax mutations in Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 85: 1146–1150. [PMC free article: PMC279723] [PubMed: 3124114]
    144.
    Micol J.L., Castelli-Gair J.E. and Garcia-Bellido A. (1990) Genetic analysis of transvection effects involving cis-regulatory elements of the Drosophila Ultrabithorax gene. Genetics 126: 365–373. [PMC free article: PMC1204191] [PubMed: 2123161]
    145.
    Mattick J.S. and Gagen M.J. (2001) The evolution of controlled multitasked gene networks: The role of introns and other noncoding RNAs in the development of complex organisms. Molecular Biology and Evolution 18: 1611–1630. [PubMed: 11504843]
    146.
    Peifer M. and Bender W. (1986) The anterobithorax and bithorax mutations of the bithorax complex. EMBO Journal 5: 2293–2303. [PMC free article: PMC1167113] [PubMed: 3023068]
    147.
    Geyer P.K., Green M.M. and Corces V.G. (1990) Tissue-specific transcriptional enhancers may act in trans on the gene located in the homologous chromosome: The molecular basis of transvection in Drosophila. EMBO Journal 9: 2247–2256. [PMC free article: PMC551949] [PubMed: 2162766]
    148.
    McCall K., O‘Connor M.B. and Bender W. (1994) Enhancer traps in the Drosophila bithorax complex mark parasegmental domains. Genetics 138: 387–399. [PMC free article: PMC1206157] [PubMed: 7828822]
    149.
    Judd B.H. (1995) Mutations of zeste that mediate transvection are recessive enhancers of position-effect variegation in Drosophila melanogaster. Genetics 141: 245–253. [PMC free article: PMC1206722] [PubMed: 8536972]
    150.
    Lim B., Heist T., Levine M. and Fukaya T. (2018) Visualization of transvection in living Drosophila embryos. Molecular Cell 70: 287–296. [PMC free article: PMC6092965] [PubMed: 29606591]
    151.
    Judd B.H. (1988) Transvection: Allelic cross talk. Cell 53: 841–843. [PubMed: 2838174]
    152.
    Wu C.T. and Morris J.R. (1999) Transvection and other homology effects. Current Opinion in Genetics and Development 9: 237–246. [PubMed: 10322135]
    153.
    Lewis P.H. (1947) New mutants report. Drosophila Information Service 21: 69.
    154.
    Gorfinkiel N., et al. (2004) The Drosophila Polycomb group gene Sex combs extra encodes the ortholog of mammalian Ring1 proteins. Mechanisms of Development 121: 449–462. [PubMed: 15147763]
    155.
    Peterson A.J., et al. (2004) Requirement for sex comb on midleg protein interactions in Drosophila polycomb group repression. Genetics 167: 1225–1239. [PMC free article: PMC1470928] [PubMed: 15280237]
    156.
    Sinclair D.A., et al. (1998) The Additional sex combs gene of Drosophila encodes a chromatin protein that binds to shared and unique Polycomb group sites on polytene chromosomes. Development 125: 1207–1216. [PubMed: 9477319]
    157.
    Ingham P.W. (1981) Trithorax: A new homoeotic mutation of Drosophila melanogaster II. The role oftrx (+) after embryogenesis. Wilhelm Roux’s Archives of Developmental Biology 190: 365–369. [PubMed: 28305297]
    158.
    Ingham P.W. (1983) Differential expression of bithorax complex genes in the absence of the extra sex combs and trithorax genes. Nature 306: 591–593. [PubMed: 24937863]
    159.
    Ingham P.W. (1984) A gene that regulates the bithorax complex differentially in larval and adult cells of Drosophila. Cell 37: 815–823. [PubMed: 6430566]
    160.
    Ingham P.W. (1985) Genetic control of the spatial pattern of selector gene expression in Drosophila. Cold Spring Harbor Symposia on Quantitative Biology 50: 201–208. [PubMed: 2420511]
    161.
    Struhl G. and Akam M. (1985) Altered distributions of Ultrabithorax transcripts in extra sex combs mutant embryos of Drosophila. EMBO Journal 4: 3259–3264. [PMC free article: PMC554652] [PubMed: 2419125]
    162.
    Kennison J.A. and Tamkun J.W. (1988) Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proceedings of the National Academy of Sciences USA 85: 8136–8140. [PMC free article: PMC282375] [PubMed: 3141923]
    163.
    Shearn A. (1989) The ash-1, ash-2 and trithorax genes of Drosophila melanogaster are functionally related. Genetics 121: 517–525. [PMC free article: PMC1203637] [PubMed: 2497049]
    164.
    Kennison J.A. (1995) The Polycomb and trithorax group proteins of Drosophila: Trans-regulators of homeotic gene function. Annual Review of Genetics 29: 289–303. [PubMed: 8825476]
    165.
    Ingham P.W. (1985) A clonal analysis of the requirement for the trithorax gene in the diversification of segments in Drosophila. Journal of Embryology and Experimental Morphology 89: 349–365. [PubMed: 4093752]
    166.
    Schuettengruber B., Bourbon H.-M., Di Croce L. and Cavalli G. (2017) Genome regulation by Polycomb and Trithorax: 70 years and counting. Cell 171: 34–57. [PubMed: 28938122]
    167.
    Schuettengruber B., Chourrout D., Vervoort M., Leblanc B. and Cavalli G. (2007) Genome regulation by polycomb and trithorax proteins. Cell 128: 735–745. [PubMed: 17320510]
    168.
    Erwin D.H. (2015) Retrospective. Eric Davidson (1937–2015). Science 350: 517. [PubMed: 26516272]
    169.
    Hood L. and Rothenberg E.V. (2015) Developmental biologist Eric H. Davidson, 1937–2015. Proceedings of the National Academy of Sciences USA 112: 13423–13425. [PMC free article: PMC4640791] [PubMed: 26499244]
    170.
    Crippa M., Davidson E.H. and Mirsky A.E. (1967) Persistence in early amphibian embryos of informational RNAs from lampbrush chromosome stage of oogenesis. Proceedings of the National Academy of Sciences USA 57: 885–892. [PMC free article: PMC224630] [PubMed: 5232368]
    171.
    Davidson E.H. (1968) Gene Activity in Early Development (Academic Press, New York).
    172.
    Davidson E.H. and Erwin D.H. (2006) Gene regulatory networks and the evolution of animal body plans. Science 311: 796–800. [PubMed: 16469913]
    173.
    Denis H. (1966) Gene expression in amphibian development II. Release of the genetic information in growing embryos. Journal of Molecular Biology 22: 285–304. [PubMed: 6008464]
    174.
    Mirsky A.E. and Ris H. (1951) The desoxyribonucleic acid content of animal cells and Its evolutionary significance. Journal of General Physiology 34: 451–462. [PMC free article: PMC2147229] [PubMed: 14824511]
    175.
    Taft R.J. and Mattick J.S. (2003) Increasing biological complexity is positively correlated with the relative genome-wide expansion of non-protein-coding DNA sequences. Genome Biology Preprint Depository. http:​//genomebiology.com/2003/5/1/P1.
    176.
    Taft R.J., Pheasant M. and Mattick J.S. (2007) The relationship between non-protein-coding DNA and eukaryotic complexity. BioEssays 29: 288–299. [PubMed: 17295292]
    177.
    Liu G., Mattick J.S. and Taft R.J. (2013) A meta-analysis of the genomic and transcriptomic composition of complex life. Cell Cycle 12: 2061–2072. [PMC free article: PMC3737309] [PubMed: 23759593]
    178.
    Davidson E.H., Klein W.H. and Britten R.J. (1977) Sequence organization in animal DNA and a speculation on hnRNA as a coordinate regulatory transcript. Developmental Biology 55: 69–84. [PubMed: 832773]
    179.
    Davidson E.H. and Britten R.J. (1979) Regulation of gene expression: Possible role of repetitive sequences. Science 204: 1052–1059. [PubMed: 451548]
    180.
    Davidson E.H. and Britten R.J. (1973) Organization, transcription, and regulation in the animal genome. Quarterly Review of Biology 48: 565–613. [PubMed: 4592421]
    181.
    Davidson E.H. (1971) Note on the control of gene expression during development. Journal of Theoretical Biology 32: 123–130. [PubMed: 5104509]
    182.
    Britten R.J. and Davidson E.H. (1971) Repetitive and non-repetitive DNA sequences and a speculation on origins of evolutionary novelty. Quarterly Review of Biology 46: 111–138. [PubMed: 5160087]
    183.
    Fedoroff N., Wellauer P.K. and Wall R. (1977) Intermolecular duplexes in heterogeneous nuclear RNA from HeLa cells. Cell 10: 597–610. [PubMed: 862021]
    184.
    Pederson T. (2009) The discovery of eukaryotic genome design and its forgotten corollary–the postulate of gene regulation by nuclear RNA. FASEB Journal 23: 2019–2021. [PubMed: 19567373]
    185.
    Davidson E.H. (2006) The Regulatory Genome: Gene Regulatory Networks In Development And Evolution (Academic Press, New York).
    186.
    Erwin D.H. and Davidson E.H. (2009) The evolution of hierarchical gene regulatory networks. Nature Reviews Genetics 10: 141–148. [PubMed: 19139764]
    187.
    Peter I.S. and Davidson E.H. (2011) Evolution of gene regulatory networks controlling body plan development. Cell 144: 970–985. [PMC free article: PMC3076009] [PubMed: 21414487]
    188.
    King M.C. and Wilson A.C. (1975) Evolution at two levels in humans and chimpanzees. Science 188: 107–116. [PubMed: 1090005]
    189.
    Jacob F. (1977) Evolution and tinkering. Science 196: 1161–1166. [PubMed: 860134]
    190.
    Arthur W. (2002) The emerging conceptual framework of evolutionary developmental biology. Nature 415: 757–764. [PubMed: 11845200]
    191.
    Carroll S.B. (2008) Evo-devo and an expanding evolutionary synthesis: A genetic theory of morphological evolution. Cell 134: 25–36. [PubMed: 18614008]
    192.
    Loehlin D.W., Ames J.R., Vaccaro K. and Carroll S.B. (2019) A major role for noncoding regulatory mutations in the evolution of enzyme activity. Proceedings of the National Academy of Sciences USA 116: 12383–12389. [PMC free article: PMC6589674] [PubMed: 31152141]
    193.
    Waddington C.H. (1969) Gene regulation in higher cells. Science 166: 639–640. [PubMed: 5823305]
    194.
    Kauffman S. (1969) Homeostasis and differentiation in random genetic control networks. Nature 224: 177–178. [PubMed: 5343519]
    195.
    Kauffman S. (1971) Gene regulation networks: A theory for their global structure and behaviors, in G. Schatten (ed.) Current Topics in Developmental Biology (Academic Press, New York). [PubMed: 5005757]
    196.
    Kauffman S. (1974) The large scale structure and dynamics of gene control circuits: An ensemble approach. Journal of Theoretical Biology 44: 167–190. [PubMed: 4595774]
    197.
    Levine M. and Davidson E.H. (2005) Gene regulatory networks for development. Proceedings of the National Academy of Sciences USA 102: 4936–4942. [PMC free article: PMC555974] [PubMed: 15788537]
    198.
    Peter I.S. and Davidson E.H. (2011) A gene regulatory network controlling the embryonic specification of endoderm. Nature 474: 635–639. [PMC free article: PMC3976212] [PubMed: 21623371]
    199.
    Peter I.S., Faure E. and Davidson E.H. (2012) Predictive computation of genomic logic processing functions in embryonic development. Proceedings of the National Academy of Sciences USA 109: 16434–16442. [PMC free article: PMC3478651] [PubMed: 22927416]
    200.
    Albert R. and Othmer H.G. (2003) The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster. Journal of Theoretical Biology 223: 1–18. [PMC free article: PMC6388622] [PubMed: 12782112]
    201.
    Davidich M.I. and Bornholdt S. (2008) Boolean network model predicts cell cycle sequence of fission yeast. PLOS ONE 3: e1672. [PMC free article: PMC2243020] [PubMed: 18301750]
    202.
    W., R. (1974) Nuclear and messenger RNA. Nature 247: 506–507. https://doi​.org/10.1038/247506a0
    203.
    Crick F. (1971) General model for the chromosomes of higher organisms. Nature 234: 25–27. [PubMed: 4942881]
    204.
    Kolodny G.M. (1973) Regulation of gene expression in eukaryotic cells. Journal of Cell Biology 59: 175a.
    205.
    Kolodny G.M. (1975) The regulation of gene expression in eukaryotic cells. Medical Hypotheses 1: 15–22. [PubMed: 1105092]
    206.
    Wise G.E. and Goldstein L. (1973) Electron microscope localization of nuclear RNA’s that shuttle between cytoplasm and nucleus and nuclear RNA’s that do not. Journal of Cell Biology 56: 129–138. [PMC free article: PMC2108845] [PubMed: 4629880]
    207.
    Goldstein L., Wise G.E. and Beeson M. (1973) Proof that certain RNAs shuttle non-randomly between cytoplasm and nucleus. Experimental Cell Research 76: 281–288. [PubMed: 4568158]
    208.
    Goldstein L. (1976) Role for small nuclear RNAs in “programming” chromosomal information? Nature 261: 519–521. [PubMed: 934289]
    209.
    Goldstein L. and Ko C. (1975) The characteristics of shuttling RNAs confirmed. Experimental Cell Research 96: 297–302. [PubMed: 1193179]
    210.
    Mandel P. and Métais P. (1948) Les acides nucleiques du plasma sanguin chez l‘homme. Comptes Rendus de l‘Académie des Sciences 142: 241–243. [PubMed: 18875018]
    211.
    Kolodny G.M., Culp L.A. and Rosenthal L.J. (1972) Secretion of RNA by normal and transformed cells. Experimental Cell Research 73: 65–72. [PubMed: 4338683]
    212.
    Kolodny G.M. (1971) Evidence for transfer of macromolecular RNA between mammalian cells in culture. Experimental Cell Research 65: 313–324. [PubMed: 4101797]
    213.
    Judd B.H. and Young M.W. (1974) An examination of the one cistron: One chromomere concept. Cold Spring Harbor Symposia on Quantitative Biology 38: 573–579. [PubMed: 4208792]
    214.
    Daneholt B. (1972) Giant RNA transcript in a Balbiani ring. Nature New Biology 240: 229–232. [PubMed: 4509163]
    215.
    Heywood S.M., Kennedy D.S. and Bester A.J. (1975) Studies concerning the mechanism by which translational-control RNA regulates protein synthesis in embryonic muscle. European Journal of Biochemistry 58: 587–593. [PubMed: 1237405]
    216.
    Bester A.J., Kennedy D.S. and Heywood S.M. (1975) Two classes of translational control RNA: Their role in the regulation of protein synthesis. Proceedings of the National Academy of Sciences USA 72: 1523–1527. [PMC free article: PMC432569] [PubMed: 1055423]
    217.
    Brawerman G. (1976) A model for the control of transcription during development. Cancer Research 36: 4278–4281. [PubMed: 975062]
    218.
    Dickson E. and Robertson H.D. (1976) Potential regulatory roles for RNA in cellular development. Cancer Research 36: 3387–3393. [PubMed: 975098]
    219.
    Robertson H.D. and Dickson E. (1975) RNA processing and the control of gene expression. Brookhaven Symposia in Biology 26: 240–266. [PubMed: 1104093]
    220.
    Rothenberg E.V. (2016) Eric Davidson: Steps to a gene regulatory network for development. Developmental Biology 412: S7–19. [PMC free article: PMC4828313] [PubMed: 26825392]
    221.
    Jacob F., Perrin D., Sanchez C. and Monod J. (2005) The operon: A group of genes with expression coordinated by an operator [Facsimile of the article in Comptes Rendus de l‘Académie des Sciences de Paris 250 (1960) 1727–1729]. Comptes Rendus Biologies 328: 514–520. [PubMed: 15999435]
    222.
    Jacob F. and Monod J. (1961) Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology 3: 318–356. [PubMed: 13718526]
    223.
    Monod J., Changeux J.P. and Jacob F. (1963) Allosteric proteins and cellular control systems. Journal of Molecular Biology 6: 306–329. [PubMed: 13936070]
    224.
    Ptashne M. (1967) Specific binding of the lambda phage repressor to lambda DNA. Nature 214: 232–234. [PubMed: 6034235]
    225.
    Maniatis T., Ptashne M. and Maurer R. (1974) Control elements in the DNA of bacteriophage lambda. Cold Spring Harbor Symposia on Quantitative Biology 38: 857–868. [PubMed: 4545512]
    226.
    Ptashne M., et al. (1980) How the lambda repressor and cro work. Cell 19: 1–11. [PubMed: 6444544]
    227.
    Deichmann U. (2016) Interview with Eric Davidson. Developmental Biology 412: S20–9. [PubMed: 26825396]
    228.
    Peter I.S. and Davidson E.H. (2009) Genomic control of patterning. International Journal of Developmental Biology 53: 707–716. [PMC free article: PMC3967875] [PubMed: 19378258]
    229.
    Peter I.S. and Davidson E.H. (2009) Modularity and design principles in the sea urchin embryo gene regulatory network. FEBS Letters 583: 3948–3958. [PMC free article: PMC2810318] [PubMed: 19932099]
    230.
    Peter I.S. and Davidson E.H. (2010) The endoderm gene regulatory network in sea urchin embryos up to mid-blastula stage. Developmental Biology 340: 188–199. [PMC free article: PMC3981691] [PubMed: 19895806]
    231.
    Peter I.S. and Davidson E.H. (2016) Implications of developmental gene regulatory networks inside and outside developmental biology. Current Topics in Developmental Biology 117: 237–251. [PubMed: 26969981]
    232.
    Peter I.S. and Davidson E.H. (2017) Assessing regulatory information in developmental gene regulatory networks. Proceedings of the National Academy of Sciences USA 114: 5862–5869. [PMC free article: PMC5468647] [PubMed: 28584110]
    233.
    Faure E., Peter I.S. and Davidson E.H. (2013) A new software package for predictive gene regulatory network modeling and redesign. Journal of Computational Biology 20: 419–423. [PMC free article: PMC3667423] [PubMed: 23614576]
    234.
    Calzone F.J., Lee J.J., Le N., Britten R.J. and Davidson E.H. (1988) A long, nontranslatable poly(A) RNA stored in the egg of the sea urchin Strongylocentrotus purpuratus. Genes & Development 2: 305–318. [PubMed: 2454211]
    235.
    Britten R.J., Baron W.F., Stout D.B. and Davidson E.H. (1988) Sources and evolution of human Alu repeated sequences. Proceedings of the National Academy of Sciences USA 85: 4770–4774. [PMC free article: PMC280517] [PubMed: 3387437]
    236.
    Britten R. (2006) Transposable elements have contributed to thousands of human proteins. Proceedings of the National Academy of Sciences USA 103: 1798–1803. [PMC free article: PMC1413650] [PubMed: 16443682]
    237.
    Britten R.J. (2010) Transposable element insertions have strongly affected human evolution. Proceedings of the National Academy of Sciences USA 107: 19945–19948. [PMC free article: PMC2993358] [PubMed: 21041622]

    Chapter 6

    1.
    Yi D. (2008) Cancer, viruses, and mass migration: Paul Berg’s venture into eukaryotic biology and the advent of recombinant DNA research and technology, 1967–1980. Journal of the History of Biology 41: 589–636. [PubMed: 19244843]
    2.
    Luria S.E. and Human M.L. (1952) A nonhereditary, host-induced variation of bacterial viruses. Journal of Bacteriology 64: 557–569. [PMC free article: PMC169391] [PubMed: 12999684]
    3.
    Bertani G. and Weigle J.J. (1953) Host controlled variation in bacterial viruses. Journal of Bacteriology 65: 113–121. [PMC free article: PMC169650] [PubMed: 13034700]
    4.
    Weigle J.J. and Bertani G. (1953) Variations of bacteriophage conditioned by host bacteria. Annales de l‘Institut Pasteur 84: 175–179. [PubMed: 13031249]
    5.
    Arber W. and Dussoix D. (1962) Host specificity of DNA produced by Escherichia coli. I. Host controlled modification of bacteriophage lambda. Journal of Molecular Biology 5: 18–36. [PubMed: 13862047]
    6.
    Dussoix D. and Arber W. (1962) Host specificity of DNA produced by Escherichia coli. II. Control over acceptance of DNA from infecting phage lambda. Journal of Molecular Biology 5: 37–49. [PubMed: 13888713]
    7.
    Arber W., Hattman S. and Dussoix D. (1963) On the host-controlled modification of bacteriophage lambda. Virology 21: 30–35. [PubMed: 14062909]
    8.
    Dussoix D. and Arber W. (1965) Host specificity of DNA produced by Escherichia coli. IV. Host specificity of infectious DNA from bacteriophage lambda. Journal of Molecular Biology 11: 238–246. [PubMed: 14292250]
    9.
    Arber W. (1965) Host-controlled modification of bacteriophage. Annual Review of Microbiology 19: 365–378. [PubMed: 5318444]
    10.
    Kuhnlein U., Linn S. and Arber W. (1969) Host specificity of DNA produced by Escherichia coli. XI. In vitro modification of phage fd replicative form. Proceedings of the National Academy of Sciences USA 63: 556–562. [PMC free article: PMC223599] [PubMed: 4895540]
    11.
    Arber W. and Linn S. (1969) DNA modification and restriction. Annual Review of Biochemistry 38: 467–500. [PubMed: 4897066]
    12.
    Lederberg S. and Meselson M. (1964) Degradation of non-replicating bacteriophage DNA in non-accepting cells. Journal of Molecular Biology 8: 623–628. [PubMed: 14187389]
    13.
    Meselson M. and Yuan R. (1968) DNA restriction enzyme from E. coli. Nature 217: 1110–1114. [PubMed: 4868368]
    14.
    Loenen W.A.M., Dryden D.T.F., Raleigh E.A., Wilson G.G. and Murray N.E. (2014) Highlights of the DNA cutters: A short history of the restriction enzymes. Nucleic Acids Research 42: 3–19. [PMC free article: PMC3874209] [PubMed: 24141096]
    15.
    Kennaway C.K. et al. (2012) Structure and operation of the DNA-translocating type I DNA restriction enzymes. Genes & Development 26: 92–104. [PMC free article: PMC3258970] [PubMed: 22215814]
    16.
    Loenen W.A.M., Dryden D.T.F., Raleigh E.A. and Wilson G.G. (2014) Type I restriction enzymes and their relatives. Nucleic Acids Research 42: 20–44. [PMC free article: PMC3874165] [PubMed: 24068554]
    17.
    Smith H.O. and Wilcox K.W. (1970) A restriction enzyme from Hemophilus influenzae. I. Purification and general properties. Journal of Molecular Biology 51: 379–391. [PubMed: 5312500]
    18.
    Kelly Jr. T.J., and Smith H.O. (1970) A restriction enzyme from Hemophilus influenzae. II. Base sequence of the recognition site. Journal of Molecular Biology 51: 393–409. [PubMed: 5312501]
    19.
    Danna K. and Nathans D. (1971) Specific cleavage of simian virus 40 DNA by restriction endonuclease of Hemophilus influenzae. Proceedings of the National Academy of Sciences USA 68: 2913–2917. [PMC free article: PMC389558] [PubMed: 4332003]
    20.
    Weiss B. and Richardson C.C. (1967) Enzymatic breakage and joining of deoxyribonucleic acid, I. Repair of single-strand breaks in DNA by an enzyme system from Escherichia coli infected with T4 bacteriophage. Proceedings of the National Academy of Sciences USA 57: 1021–1028. [PMC free article: PMC224649] [PubMed: 5340583]
    21.
    Jackson D.A., Symons R.H. and Berg P. (1972) Biochemical method for inserting new genetic information into DNA of Simian Virus 40: Circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proceedings of the National Academy of Sciences USA 69: 2904–2909. [PMC free article: PMC389671] [PubMed: 4342968]
    22.
    Cohen S.N. (2013) DNA cloning: A personal view after 40 years. Proceedings of the National Academy of Sciences USA 110: 15521–15529. [PMC free article: PMC3785787] [PubMed: 24043817]
    23.
    Boyer H.W. (1971) DNA restriction and modification mechanisms in bacteria. Annual Review of Microbiology 25: 153–176. [PubMed: 4949033]
    24.
    Cohen S.N., Chang A.C.Y., Boyer H.W. and Helling R.B. (1973) Construction of biologically functional bacterial plasmids in vitro. Proceedings of the National Academy of Sciences USA 70: 3240–3244. [PMC free article: PMC427208] [PubMed: 4594039]
    25.
    Chang A.C.Y. and Cohen S.N. (1974) Genome construction between bacterial species in vitro: Replication and expression of Staphylococcus plasmid genes in Escherichia coli. Proceedings of the National Academy of Sciences USA 71: 1030–1034. [PMC free article: PMC388155] [PubMed: 4598290]
    26.
    Morrow J.F., et al. (1974) Replication and transcription of eukaryotic DNA in Esherichia coli. Proceedings of the National Academy of Sciences USA 71: 1743–1747. [PMC free article: PMC388315] [PubMed: 4600264]
    27.
    Berg P. and Singer M.F. (1995) The recombinant DNA controversy: Twenty years later. Proceedings of the National Academy of Sciences USA 92: 9011–9013. [PMC free article: PMC40913] [PubMed: 7568062]
    28.
    Berg P. (2008) Asilomar 1975: DNA modification secured. Nature 455: 290–291. [PubMed: 18800118]
    29.
    Bolivar F., et al. (1977) Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. Gene 2: 95–113. [PubMed: 344137]
    30.
    Norrander J., Kempe T. and Messing J. (1983) Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene 26: 101–106. [PubMed: 6323249]
    31.
    Vieira J. and Messing J. (1982) The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene 19: 259–268. [PubMed: 6295879]
    32.
    Yanisch-Perron C., Vieira J. and Messing J. (1985) Improved M13 phage cloning vectors and host strains: Nucleotide sequences of the M13mp18 and pUC19 vectors. Gene 33: 103–119. [PubMed: 2985470]
    33.
    Dean D. (1981) A plasmid cloning vector for the direct selection of strains carrying recombinant plasmids. Gene 15: 99–102. [PubMed: 6271634]
    34.
    Polisky B., Bishop R.J. and Gelfand D.H. (1976) A plasmid cloning vehicle allowing regulated expression of eukaryotic DNA in bacteria. Proceedings of the National Academy of Sciences USA 73: 3900–3904. [PMC free article: PMC431258] [PubMed: 1069275]
    35.
    Young C.L., Britton Z.T. and Robinson A.S. (2012) Recombinant protein expression and purification: A comprehensive review of affinity tags and microbial applications. Biotechnology Journal 7: 620–634. [PubMed: 22442034]
    36.
    Maniatis T., Fritsch E.F. and Sambrook J. (1982) Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, New York).
    37.
    Various (1988) Current Protocols in Molecular Biology (John Wiley & Sons, New York).
    38.
    Gill K.P. and Denham M. (2020) Optimized transgene delivery using third-generation lentiviruses. Current Protocols in Molecular Biology 133: e125. [PMC free article: PMC7583475] [PubMed: 32986282]
    39.
    Nodelman I.M., Patel A., Levendosky R.F. and Bowman G.D. (2020) Reconstitution and purification of nucleosomes with recombinant histones and purified DNA. Current Protocols in Molecular Biology 133: e130. [PMC free article: PMC7735289] [PubMed: 33305911]
    40.
    Reimer K.A. and Neugebauer K.M. (2020) Preparation of mammalian nascent RNA for long read sequencing. Current Protocols in Molecular Biology 133: e128. [PMC free article: PMC7586757] [PubMed: 33085989]
    41.
    Vasquez C.A., Cowan Q.T. and Komor A.C. (2020) Base editing in human cells to produce single-nucleotide-variant clonal cell lines. Current Protocols in Molecular Biology 133: e129. [PMC free article: PMC7654285] [PubMed: 33151638]
    42.
    Baltimore D. (1970) Viral RNA-dependent DNA polymerase: RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226: 1209–1211. [PubMed: 4316300]
    43.
    Temin H.M. and Mizutani S. (1970) RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226: 1211–1213. [PubMed: 4316301]
    44.
    Michelson A.M. and Todd A.R. (1955) Nucleotides part XXXII. Synthesis of a dithymidine dinucleotide containing a 3′: 5′-internucleotidic linkage. Journal of the Chemical Society (Resumed): 2632–2638. https://doi​.org/10.1039/JR9550002632
    45.
    Hall R.H., Todd A. and Webb R.F. (1957) Nucleotides. Part XLI. Mixed anhydrides as intermediates in the synthesis of dinucleoside phosphates. Journal of the Chemical Society 1957: 3291–3296.
    46.
    Todd A. (1958) Synthesis in the study of nucleotides; basic work on phosphorylation opens the way to an attack on nucleic acids and nucleotide coenzymes. Science 127: 787–792. [PubMed: 13543331]
    47.
    Gilham P.T. and Khorana H.G. (1958) Studies on polynucleotides. I. A new and general method for the chemical synthesis of the C5″-C3″ internucleotidic linkage. Syntheses of deoxyribodinucleotides. Journal of the American Chemical Society 80: 6212–6222.
    48.
    Letsinger R.L. and Ogilvie K.K. (1969) Nucleotide chemistry. XIII. Synthesis of oligothymidylates via phosphotriester intermediates. Journal of the American Chemical Society 91: 3350–3355.
    49.
    Letsinger R.L., Finnan J.L., Heavner G.A. and Lunsford W.B. (1975) Nucleotide chemistry. XX. Phosphite coupling procedure for generating internucleotide links. Journal of the American Chemical Society 97: 3278–3279. [PubMed: 1133350]
    50.
    Reese C.B. (1978) The chemical synthesis of oligo- and poly-nucleotides by the phosphotriester approach. Tetrahedron 34: 3143–3179.
    51.
    Reese C.B. (2005) Oligo- and poly-nucleotides: 50 years of chemical synthesis. Organic & Biomolecular Chemistry 3: 3851–3868. [PubMed: 16312051]
    52.
    Matteucci M.D. and Caruthers M.H. (1981) Synthesis of deoxyoligonucleotides on a polymer support. Journal of the American Chemical Society 103: 3185–3191.
    53.
    Beaucage S.L. and Caruthers M.H. (1981) Deoxynucleoside phosphoramidites—A new class of key intermediates for deoxypolynucleotide synthesis. Tetrahedron Letters 22: 1859–1862.
    54.
    Goodchild J. (1990) Conjugates of oligonucleotides and modified oligonucleotides: A review of their synthesis and properties. Bioconjugate Chemistry 1: 165–187. [PubMed: 1965782]
    55.
    Beaucage S.L. and Iyer R.P. (1992) Advances in the synthesis of oligonucleotides by the phosphoramidite approach. Tetrahedron 48: 2223–2311.
    56.
    Roy S. and Caruthers M. (2013) Synthesis of DNA/RNA and their analogs via phosphoramidite and H-phosphonate chemistries. Molecules 18: 14268–14284. [PMC free article: PMC6270087] [PubMed: 24252996]
    57.
    Roy B., Depaix A., Périgaud C. and Peyrottes S. (2016) Recent trends in nucleotide synthesis. Chemical Reviews 116: 7854–7897. [PubMed: 27319940]
    58.
    Smith C.I.E. and Zain R. (2019) Therapeutic oligonucleotides: State of the art. Annual Review of Pharmacology and Toxicology 59: 605–630. [PubMed: 30285540]
    59.
    Bonde M.T. et al. (2015) Direct mutagenesis of thousands of genomic targets using microarray-derived oligonucleotides. ACS Synthetic Biology 4: 17–22. [PMC free article: PMC4304438] [PubMed: 24856730]
    60.
    Palluk S. et al. (2018) De novo DNA synthesis using polymerase-nucleotide conjugates. Nature Biotechnology 36: 645–650. [PubMed: 29912208]
    61.
    Eisenstein M. (2020) Enzymatic DNA synthesis enters new phase. Nature Biotechnology 38: 1113–1115. [PubMed: 33020638]
    62.
    Kosuri S. and Church G.M. (2014) Large-scale de novo DNA synthesis: Technologies and applications. Nature Methods 11: 499–507. [PMC free article: PMC7098426] [PubMed: 24781323]
    63.
    Southern E.M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. Journal of Molecular Biology 98: 503–517. [PubMed: 1195397]
    64.
    Alwine J.C., Kemp D.J. and Stark G.R. (1977) Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes. Proceedings of the National Academy of Sciences USA 74: 5350–5354. [PMC free article: PMC431715] [PubMed: 414220]
    65.
    Towbin H., Staehelin T. and Gordon J. (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proceedings of the National Academy of Sciences USA 76: 4350–4354. [PMC free article: PMC411572] [PubMed: 388439]
    66.
    Burnette W.N. (1981) “Western Blotting”: Electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Analytical Biochemistry 112: 195–203. [PubMed: 6266278]
    67.
    Moritz C.P. (2020) 40 years Western blotting: A scientific birthday toast. Journal of Proteomics 212: 103575. [PubMed: 31706026]
    68.
    Bowen B., Steinberg J., Laemmli U.K. and Weintraub H. (1980) The detection of DNA-binding proteins by protein blotting. Nucleic Acids Research 8: 1–20. [PMC free article: PMC327239] [PubMed: 6243775]
    69.
    Qian Z.W. and Wilusz J. (1993) Cloning of a cDNA encoding an RNA binding protein by screening expression libraries using a Northwestern strategy. Analytical Biochemistry 212: 547–554. [PubMed: 8214599]
    70.
    Grunstein M. and Hogness D.S. (1975) Colony hybridization: A method for the isolation of cloned DNAs that contain a specific gene. Proceedings of the National Academy of Sciences USA 72: 3961–3965. [PMC free article: PMC433117] [PubMed: 1105573]
    71.
    Brownlee G.G., Sanger F. and Barrell B.G. (1967) Nucleotide sequence of 5S-ribosomal RNA from Escherichia coli. Nature 215: 735–736. [PubMed: 4862513]
    72.
    Brownlee G.G., Sanger F. and Barrell B.G. (1968) The sequence of 5 s ribosomal ribonucleic acid. Journal of Molecular Biology 34: 379–412. [PubMed: 4938553]
    73.
    Wu R. and Kaiser A.D. (1968) Structure and base sequence in the cohesive ends of bacteriophage lambda DNA. Journal of Molecular Biology 35: 523–537. [PubMed: 4299833]
    74.
    Wu R. and Taylor E. (1971) Nucleotide sequence analysis of DNA. II. Complete nucleotide sequence of the cohesive ends of bacteriophage lambda DNA. Journal of Molecular Biology 57: 491–511. [PubMed: 4931680]
    75.
    Wu R. (1972) Nucleotide sequence analysis of DNA. Nature New Biology 236: 198–200. [PubMed: 4553110]
    76.
    Min Jou W., Haegeman G., Ysebaert M. and Fiers W. (1972) Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein. Nature 237: 82–88. [PubMed: 4555447]
    77.
    Fiers W. et al. (1976) Complete nucleotide sequence of bacteriophage MS2 RNA: Primary and secondary structure of the replicase gene. Nature 260: 500–507. [PubMed: 1264203]
    78.
    Maxam A.M. and Gilbert W. (1977) A new method for sequencing DNA. Proceedings of the National Academy of Sciences USA 74: 560–564. [PMC free article: PMC392330] [PubMed: 265521]
    79.
    Sanger F. et al. (1977) Nucleotide sequence of bacteriophage phi X174 DNA. Nature 265: 687–695. [PubMed: 870828]
    80.
    Sanger F., Nicklen S. and Coulson A.R. (1977) DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences USA 74: 5463–5467. [PMC free article: PMC431765] [PubMed: 271968]
    81.
    Smith L.M. et al. (1986) Fluorescence detection in automated DNA sequence analysis. Nature 321: 674–679. [PubMed: 3713851]
    82.
    Prober J.M. et al. (1987) A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides. Science 238: 336–341. [PubMed: 2443975]
    83.
    Watson J.D. and Cook-Deegan R.M. (1991) Origins of the human genome project. FASEB Journal 5: 8–11. [PubMed: 1991595]
    84.
    Bentley D.R. et al. (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456: 53–59. [PMC free article: PMC2581791] [PubMed: 18987734]
    85.
    Heather J.M. and Chain B. (2016) The sequence of sequencers: The history of sequencing DNA. Genomics 107: 1–8. [PMC free article: PMC4727787] [PubMed: 26554401]
    86.
    Foret F., Klepárník K. and Minárik M. (2019) Nucleic acids: Chromatographic and electrophoretic methods, in P. Worsfold, A. Townshend and C. Poole (eds.) Encyclopedia of Analytical Science (Third edition) (Academic Press, New York).
    87.
    Wilson J.T., Forget B.G., Wilson L.B. and Weissman S.M. (1977) Human globin messenger RNA: Importance of cloning for structural analysis. Science 196: 200–202. [PubMed: 847468]
    88.
    Begley C.G. and Ellis L.M. (2012) Raise standards for preclinical cancer research. Nature 483: 531–533. [PubMed: 22460880]
    89.
    Freedman L.P., Cockburn I.M. and Simcoe T.S. (2015) The economics of reproducibility in preclinical research. PLOS Biology 13: e1002165. [PMC free article: PMC4461318] [PubMed: 26057340]
    90.
    Begley C.G. and Ioannidis John P.A. (2015) Reproducibility in science. Circulation Research 116: 116–126. [PubMed: 25552691]
    91.
    Ioannidis J.P.A. (2017) Acknowledging and overcoming nonreproducibility in basic and preclinical research. Journal of the American Medical Association 317: 1019–1020. [PubMed: 28192565]
    92.
    Morange M. (1998) A History of Molecular Biology (Harvard University Press, New York).
    93.
    Finn R.D. et al. (2008) The Pfam protein families database. Nucleic Acids Research 36: D281–8. [PMC free article: PMC2238907] [PubMed: 18039703]
    94.
    El-Gebali S. et al. (2019) The Pfam protein families database in 2019. Nucleic Acids Research 47: D427–32. [PMC free article: PMC6324024] [PubMed: 30357350]
    95.
    Rubin G.M. and Lewis E.B. (2000) A brief history of Drosophila’s contributions to genome research. Science 287: 2216–2218. [PubMed: 10731135]
    96.
    Bender W., Spierer P., Hogness D.S. and Chambon P. (1983) Chromosomal walking and jumping to isolate DNA from the Ace and rosy loci and the bithorax complex in Drosophila melanogaster. Journal of Molecular Biology 168: 17–33. [PubMed: 6410077]
    97.
    Bender W. et al. (1983) Molecular genetics of the bithorax complex in Drosophila melanogaster. Science 221: 23–29. [PubMed: 17737996]
    98.
    Garber R.L., Kuroiwa A. and Gehring W.J. (1983) Genomic and cDNA clones of the homeotic locus Antennapedia in Drosophila. EMBO Journal 2: 2027–2036. [PMC free article: PMC555405] [PubMed: 6416827]
    99.
    McGinnis W., Levine M.S., Hafen E., Kuroiwa A. and Gehring W.J. (1984) A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and Bithorax complexes. Nature 308: 428–433. [PubMed: 6323992]
    100.
    Scott M.P. and Weiner A.J. (1984) Structural relationships among genes that control development - sequence homology between the Antennapedia, Ultrabithorax, and Fushi Tarazu loci of Drosophila. Proceedings of the National Academy of Sciences USA 81: 4115–4119. [PMC free article: PMC345379] [PubMed: 6330741]
    101.
    Akam M.E., Martinez-Arias A., Weinzierl R. and Wilde C.D. (1985) Function and expression of ultrabithorax in the Drosophila embryo. Cold Spring Harbor Symposia on Quantitative Biology 50: 195–200. [PubMed: 3868478]
    102.
    Irish V.F., Martinez-Arias A. and Akam M. (1989) Spatial regulation of the Antennapedia and Ultrabithorax homeotic genes during Drosophila early development. EMBO Journal 8: 1527–1537. [PMC free article: PMC400984] [PubMed: 2569971]
    103.
    Sanchez-Herrero E. and Akam M. (1989) Spatially ordered transcription of regulatory DNA in the bithorax complex of Drosophila. Development 107: 321–329. [PubMed: 2632227]
    104.
    Müller M.M., Carrasco A.E. and DeRobertis E.M. (1984) A homeo-box-containing gene expressed during oogenesis in xenopus. Cell 39: 157–162. [PubMed: 6207937]
    105.
    Gehring W.J. et al. (1994) Homeodomain-DNA recognition. Cell 78: 211–223. [PubMed: 8044836]
    106.
    Gehring W.J. and Ikeo K. (1999) Pax 6: Mastering eye morphogenesis and eye evolution. Trends in Genetics 15: 371–377. [PubMed: 10461206]
    107.
    Duboule D. and Dollé P. (1989) The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO Journal 8: 1497–1505. [PMC free article: PMC400980] [PubMed: 2569969]
    108.
    Graham A., Papalopulu N. and Krumlauf R. (1989) The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell 57: 367–378. [PubMed: 2566383]
    109.
    Akam M. (1989) Hox and HOM: Homologous gene clusters in insects and vertebrates. Cell 57: 347–349. [PubMed: 2566382]
    110.
    Tournier-Lasserve E., Odenwald W.F., Garbern J., Trojanowski J. and Lazzarini R.A. (1989) Remarkable intron and exon sequence conservation in human and mouse homeobox Hox1.3 genes. Molecular and Cellular Biology 9: 2273–2278. [PMC free article: PMC363029] [PubMed: 2568583]
    111.
    Potter S.S. and Branford W.W. (1998) Evolutionary conservation and tissue-specific processing of Hoxa 11 antisense transcripts. Mammalian Genome 9: 799–806. [PubMed: 9745033]
    112.
    Hahn H. et al. (1996) Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85: 841–851. [PubMed: 8681379]
    113.
    Johnson R.L. et al. (1996) Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272: 1668–1671. [PubMed: 8658145]
    114.
    Davies P.C.W. and Lineweaver C.H. (2011) Cancer tumors as Metazoa 1.0: Tapping genes of ancient ancestors. Physical Biology 8: 015001. [PMC free article: PMC3148211] [PubMed: 21301065]
    115.
    Trigos A.S., Pearson R.B., Papenfuss A.T. and Goode D.L. (2019) Somatic mutations in early metazoan genes disrupt regulatory links between unicellular and multicellular genes in cancer. eLife 8: e40947. [PMC free article: PMC6402835] [PubMed: 30803482]
    116.
    Rous P. (1911) A sarcoma of the fowl transmissible by an agent separable from the tumor cells. Journal of Experimental Medicine 13: 397–411. [PMC free article: PMC2124874] [PubMed: 19867421]
    117.
    Ellerman V. and Bang O. (1908) Experimentelle leukämie bei Hühnerin. Zentralblatt für Bakteriologie, Mikrobiologie und Hygiene 46: 595–609.
    118.
    Fujinami A. and Inamoto K. (1914) Untersuchungen über das Vorkommen und die klinische Bedeutung der Sarkome beim Hausgeflügel. Zeitschrift für Krebsforschung 14: 94–119.
    119.
    Martin G.S. (2004) The road to Src. Oncogene 23: 7910–7917. [PubMed: 15489909]
    120.
    Irby R.B. and Yeatman T.J. (2000) Role of Src expression and activation in human cancer. Oncogene 19: 5636–5642. [PubMed: 11114744]
    121.
    Croce C.M. (2008) Oncogenes and cancer. New England Journal of Medicine 358: 502–511. [PubMed: 18234754]
    122.
    Peiris M.N., Li F. and Donoghue D.J. (2019) BCR: A promiscuous fusion partner in hematopoietic disorders. Oncotarget 10: 2738–2754. [PMC free article: PMC6505627] [PubMed: 31105873]
    123.
    Knudson A.G. (1971) Mutation and cancer: Statistical study of retinoblastoma. Proceedings of the National Academy of Sciences USA 68: 820–823. [PMC free article: PMC389051] [PubMed: 5279523]
    124.
    Du W. and Pogoriler J. (2006) Retinoblastoma family genes. Oncogene 25: 5190–5200. [PMC free article: PMC1899835] [PubMed: 16936737]
    125.
    Berry J.L. et al. (2019) The RB1 story: Characterization and cloning of the first tumor suppressor gene. Genes 10: 879. [PMC free article: PMC6895859] [PubMed: 31683923]
    126.
    Levine A.J. and Oren M. (2009) The first 30 years of p53: Growing ever more complex. Nature Reviews Cancer 9: 749–758. [PMC free article: PMC2771725] [PubMed: 19776744]
    127.
    Lane D. and Levine A. (2010) p53 research: The past thirty years and the next thirty years. Cold Spring Harbor Perspectives in Biology 2: a000893. [PMC free article: PMC2982174] [PubMed: 20463001]
    128.
    Sherr C.J. (2004) Principles of tumor suppression. Cell 116: 235–246. [PubMed: 14744434]
    129.
    Friedrich G. and Soriano P. (1991) Promoter traps in embryonic stem cells: A genetic screen to identify and mutate developmental genes in mice. Genes & Development 5: 1513–1523. [PubMed: 1653172]
    130.
    Irion S. et al. (2007) Identification and targeting of the ROSA26 locus in human embryonic stem cells. Nature Biotechnology 25: 1477–1482. [PubMed: 18037879]
    131.
    Li X. et al. (2014) Rosa26-targeted swine models for stable gene over-expression and Cre-mediated lineage tracing. Cell Research 24: 501–504. [PMC free article: PMC3975497] [PubMed: 24503648]
    132.
    Yang D. et al. (2016) Identification and characterization of rabbit ROSA26 for gene knock-in and stable reporter gene expression. Scientific Reports 6: 25161. [PMC free article: PMC4846827] [PubMed: 27117226]
    133.
    Zambrowicz B.P. et al. (1997) Disruption of overlapping transcripts in the ROSA βgeo 26 gene trap strain leads to widespread expression of β-galactosidase in mouse embryos and  hematopoietic cells. Proceedings of the National Academy of Sciences USA 94: 3789–3794. [PMC free article: PMC20519] [PubMed: 9108056]
    134.
    Dolgin E. (2017) The most popular genes in the human genome. Nature 551: 427–431. [PubMed: 29168817]
    135.
    Levitt N.C. and Hickson I.D. (2002) Caretaker tumour suppressor genes that defend genome integrity. Trends in Molecular Medicine 8: 179–186. [PubMed: 11927276]
    136.
    Papamichos-Chronakis M. and Peterson C.L. (2013) Chromatin and the genome integrity network. Nature Reviews Genetics 14: 62–75. [PMC free article: PMC3731064] [PubMed: 23247436]
    137.
    Oki E., Oda S., Maehara Y. and Sugimachi K. (1999) Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair. Oncogene 18: 2143–2147. [PubMed: 10321739]
    138.
    Schumacher T.N., Scheper W. and Kvistborg P. (2019) Cancer neoantigens. Annual Review of Immunology 37: 173–200. [PubMed: 30550719]
    139.
    Bhullar K.S. et al. (2018) Kinase-targeted cancer therapies: Progress, challenges and future directions. Molecular Cancer 17: 48. [PMC free article: PMC5817855] [PubMed: 29455673]
    140.
    Samstein R.M. et al. (2019) Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nature Genetics 51: 202–206. [PMC free article: PMC6365097] [PubMed: 30643254]
    141.
    Blass E. and Ott P.A. (2021) Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nature Reviews Clinical Oncology 18: 215–229. [PMC free article: PMC7816749] [PubMed: 33473220]
    142.
    Sterner R.C. and Sterner R.M. (2021) CAR-T cell therapy: Current limitations and potential strategies. Blood Cancer Journal 11: 69. [PMC free article: PMC8024391] [PubMed: 33824268]
    143.
    Nemazee D. (2000) Receptor selection in B and T lymphocytes. Annual Review of Immunology 18: 19–51. [PMC free article: PMC3822044] [PubMed: 10837051]
    144.
    Cumano A. et al. (2019) New molecular insights into immune cell development. Annual Review of Immunology 37: 497–519. [PubMed: 31026413]
    145.
    Cohn M. et al. (2007) Reflections on the clonal-selection theory. Nature Reviews Immunology 7: 823–830. [PubMed: 17893695]
    146.
    Oppenheim J.J. (2001) Cytokines: Past, present, and future. International Journal of Hematology 74: 3–8. [PubMed: 11530802]
    147.
    Köhler G. and Milstein C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256: 495–497. [PubMed: 1172191]
    148.
    Winter G. and Harris W.J. (1993) Humanized antibodies. Immunology Today 14: 243–246. [PubMed: 8397764]
    149.
    Tsien R.Y. (1998) The green fluorescent protein. Annual Review of Biochemistry 67: 509–544. [PubMed: 9759496]
    150.
    Ow D.W. et al. (1986) Transient and stable expression of the firefly luciferase gene in plant cells and transgenic plants. Science 234: 856–859. [PubMed: 17758108]
    151.
    Roda A., Pasini P., Mirasoli M., Michelini E. and Guardigli M. (2004) Biotechnological applications of bioluminescence and chemiluminescence. Trends in Biotechnology 22: 295–303. [PubMed: 15158059]
    152.
    Sherkow J.S. and Greely H.T. (2015) The history of patenting genetic material. Annual Review of Genetics 49: 161–182. [PubMed: 26442843]
    153.
    Rehman W., Arfons L.M. and Lazarus H.M. (2011) The rise, fall and subsequent triumph of thalidomide: Lessons learned in drug development. Therapeutic Advances in Hematology 2: 291–308. [PMC free article: PMC3573415] [PubMed: 23556097]
    154.
    Mullis K. et al. (1986) Specific enzymatic amplification of DNA in vitro: The polymerase chain reaction. Cold Spring Harbor Symposia on Quantitative Biology 51: 263–273. [PubMed: 3472723]
    155.
    Saiki R.K. et al. (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239: 487–491. [PubMed: 2448875]
    156.
    Brock T.D. (1995) The road to Yellowstone—and beyond. Annual Review of Microbiology 49: 1–29. [PubMed: 8561455]
    157.
    158.
    Adams M.D. et al. (1992) Sequence identification of 2,375 human brain genes. Nature 355: 632–634. [PubMed: 1538749]
    159.
    Roberts L. (1991) Genome patent fight erupts. Science 254: 184–186. [PubMed: 1925568]
    160.
    Rounsley S.D. et al. (1996) The construction of Arabidopsis expressed sequence tag assemblies. A new resource to facilitate gene identification. Plant Physiology 112: 1177–1183. [PMC free article: PMC158044] [PubMed: 8938416]
    161.
    Adams M.D. et al. (1994) A model for high-throughput automated DNA sequencing and analysis core facilities. Nature 368: 474–475. [PubMed: 8133896]
    162.
    Venter J.C., Smith H.O. and Hood L. (1996) A new strategy for genome sequencing. Nature 381: 364–366. [PubMed: 8632789]
    163.
    Venter J.C. et al. (1998) Shotgun sequencing of the human genome. Science 280: 1540–1542. [PubMed: 9644018]
    164.
    Weber J.L. and Myers E.W. (1997) Human whole-genome shotgun sequencing. Genome Research 7: 401–409. [PubMed: 9149936]
    165.
    Fritsch E.F., Lawn R.M. and Maniatis T. (1979) Characterisation of deletions which affect the expression of fetal globin genes in man. Nature 279: 598–603. [PubMed: 450109]
    166.
    Bell G.I., Karam J.H. and Rutter W.J. (1981) Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proceedings of the National Academy of Sciences USA 78: 5759–5763. [PMC free article: PMC348853] [PubMed: 6272317]
    167.
    Jagadeeswaran P., Tuan D., Forget B.G. and Weissman S.M. (1982) A gene deletion ending at the midpoint of a repetitive DNA sequence in one form of hereditary persistence of fetal haemoglobin. Nature 296: 469–470. [PubMed: 6174873]
    168.
    Rees A., Stocks J., Shoulders C.C., Galton D.J. and Baralle F.E. (1983) DNA polymorphism adjacent to human apoprotein A-1 gene: Relation to hypertriglyceridaemia. Lancet 321: 444–446. [PubMed: 6131168]
    169.
    Clark M.B. et al. (2015) Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing. Nature Methods 12: 339–342. [PubMed: 25751143]
    170.
    Gloss B.S. and Dinger M.E. (2016) The specificity of long noncoding RNA expression. Biochimica et Biophysica Acta 1859: 16–22. [PubMed: 26297315]
    171.
    Deveson I.W., Hardwick S.A., Mercer T.R. and Mattick J.S. (2017) The dimensions, dynamics, and relevance of the mammalian noncoding transcriptome. Trends in Genetics 33: 464–478. [PubMed: 28535931]
    172.
    Müller J.B. et al. (2020) The proteome landscape of the kingdoms of life. Nature 582: 592–596. [PubMed: 32555458]
    173.
    Gerstberger S., Hafner M. and Tuschl T. (2014) A census of human RNA-binding proteins. Nature Reviews Genetics 15: 829–845. [PubMed: 25365966]
    174.
    Hentze M.W., Castello A., Schwarzl T. and Preiss T. (2018) A brave new world of RNA-binding proteins. Nature Reviews Molecular Cell Biology 19: 327–341. [PubMed: 29339797]

    Chapter 7

    1.
    Swift H. (1950) The constancy of desoxyribose nucleic acid in plant nuclei. Proceedings of the National Academy of Sciences USA 36: 643–654. [PMC free article: PMC1063260] [PubMed: 14808154]
    2.
    Britten R.J. and Davidson E.H. (1969) Gene regulation for higher cells: A theory. Science 165: 349–357. [PubMed: 5789433]
    3.
    Sparrow A.H., Price H.J. and Underbrink A.G. (1972) A survey of DNA content per cell and per chromosome of prokaryotic and eukaryotic organisms: Some evolutionary considerations. Brookhaven Symposia in Biology 23: 451–494. [PubMed: 4558510]
    4.
    Tjio J.H. and Levan A. (1956) The chromosome number of man. Hereditas 42: 1–6.
    5.
    Gartler S.M. (2006) The chromosome number in humans: A brief history. Nature Reviews Genetics 7: 655–660. [PubMed: 16847465]
    6.
    Mirsky A.E. and Ris H. (1951) The desoxyribonucleic acid content of animal cells and its evolutionary significance. Journal of General Physiology 34: 451–462. [PMC free article: PMC2147229] [PubMed: 14824511]
    7.
    Gregory T.R. (2001) Coincidence, coevolution, or causation? DNA content, cellsize, and the C-value enigma. Biological Reviews 76: 65–101. [PubMed: 11325054]
    8.
    Palazzo A.F. and Gregory T.R. (2014) The case for junk DNA. PLOS Genetics 10: e1004351. [PMC free article: PMC4014423] [PubMed: 24809441]
    9.
    Thomas Jr. C.A. (1971) The genetic organization of chromosomes. Annual Review of Genetics 5: 237–256. [PubMed: 16097657]
    10.
    Gregory T.R. and Hebert P.D.N. (1999) The modulation of DNA content: Proximate causes and ultimate consequences. Genome Research 9: 317–324. [PubMed: 10207154]
    11.
    Cavalier-Smith T. (1978) Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the DNA C-value paradox. Journal of Cell Science 34: 247–278. [PubMed: 372199]
    12.
    Cavalier-Smith T. (1982) Skeletal DNA and the evolution of genome size. Annual Review of Biophysics and Bioengineering 11: 273–302. [PubMed: 7049065]
    13.
    Beaton M.J. and Cavalier-Smith T. (1999) Eukaryotic non-coding DNA is functional: Evidence from the differential scaling of cryptomonad genomes. Proceedings of the Royal Society B: Biological Sciences 266: 2053–2059. [PMC free article: PMC1690321] [PubMed: 10902541]
    14.
    Hardie D.C. and Hebert P.D.N. (2003) The nucleotypic effects of cellular DNA content in cartilaginous and ray-finned fishes. Genome 46: 683–706. [PubMed: 12897876]
    15.
    Marshall W.F. et al. (2012) What determines cell size? BMC Biology 10: 101. [PMC free article: PMC3522064] [PubMed: 23241366]
    16.
    Fedoroff N.V. (2012) Transposable elements, epigenetics, and genome evolution. Science 338: 758–767. [PubMed: 23145453]
    17.
    Moore G.P. (1984) The C-value paradox. BioScience 34: 425–429.
    18.
    Byers T.J. (1986) Molecular biology of DNA in Acanthamoeba, Amoeba, Entamoeba, and Naegleria. International Review of Cytology 99: 311–341. [PubMed: 3514511]
    19.
    Otto S.P. and Whitton J. (2000) Polyploid incidence and evolution. Annual Review of Genetics 34: 401–437. [PubMed: 11092833]
    20.
    Adams K.L. and Wendel J.F. (2005) Polyploidy and genome evolution in plants. Current Opinion in Plant Biology 8: 135–141. [PubMed: 15752992]
    21.
    Taft R.J., Pheasant M. and Mattick J.S. (2007) The relationship between non-protein-coding DNA and eukaryotic complexity. BioEssays 29: 288–299. [PubMed: 17295292]
    22.
    Metcalfe C.J., Filée J., Germon I., Joss J. and Casane D. (2012) Evolution of the Australian lungfish (Neoceratodus forsteri) genome: A major role for CR1 and L2 LINE elements. Molecular Biology and Evolution 29: 3529–3539. [PubMed: 22734051]
    23.
    Sun C. et al. (2012) LTR retrotransposons contribute to genomic gigantism in plethodontid salamanders. Genome Biology and Evolution 4: 168–183. [PMC free article: PMC3318908] [PubMed: 22200636]
    24.
    Wu C. and Lu J. (2019) Diversification of transposable elements in Arthropods and its impact on genome evolution. Genes 10: 338. [PMC free article: PMC6562904] [PubMed: 31064091]
    25.
    Petersen M. et al. (2019) Diversity and evolution of the transposable element repertoire in arthropods with particular reference to insects. BMC Evolutionary Biology 19: 11. [PMC free article: PMC6327564] [PubMed: 30626321]
    26.
    Wong W.Y. et al. (2019) Expansion of a single transposable element family is associated with genome-size increase and radiation in the genus Hydra. Proceedings of the National Academy of Sciences USA 116: 22915–22917. [PMC free article: PMC6859323] [PubMed: 31659034]
    27.
    Liu G., Mattick J.S. and Taft R.J. (2013) A meta-analysis of the genomic and transcriptomic composition of complex life. Cell Cycle 12: 2061–2072. [PMC free article: PMC3737309] [PubMed: 23759593]
    28.
    Bird A.P. (1995) Gene number, noise reduction and biological complexity. Trends in Genetics 11: 94–100. [PubMed: 7732579]
    29.
    Ohno S. (1970) Evolution by Gene Duplication (Springer-Verlag, New York).
    30.
    Zhang J. (2003) Evolution by gene duplication: An update. Trends in Ecology & Evolution 18: 292–298.
    31.
    Wolfe K.H. (2015) Origin of the yeast whole-genome duplication. PLOS Biology 13: e1002221. [PMC free article: PMC4529243] [PubMed: 26252643]
    32.
    McLysaght A., Hokamp K. and Wolfe K.H. (2002) Extensive genomic duplication during early chordate evolution. Nature Genetics 31: 200–204. [PubMed: 12032567]
    33.
    Sharp A.J. et al. (2005) Segmental duplications and copy-number variation in the human genome. American Journal of Human Genetics 77: 78–88. [PMC free article: PMC1226196] [PubMed: 15918152]
    34.
    Ozkan H., Levy A.A. and Feldman M. (2001) Allopolyploidy-induced rapid genome evolution in the wheat (Aegilops-Triticum) group. Plant Cell 13: 1735–1747. [PMC free article: PMC139130] [PubMed: 11487689]
    35.
    Roose M.L. and Gottlieb L.D. (1976) Genetic and biochemical consequences of polyploidy in Tragopogon. Evolution 30: 818–830. [PubMed: 28563335]
    36.
    Levin D.A. (1983) Polyploidy and novelty in flowering plants. American Naturalist 122: 1–25.
    37.
    Lamichhaney S. et al. (2018) Rapid hybrid speciation in Darwin’s finches. Science 359: 224–228. [PubMed: 29170277]
    38.
    Jacques P.-É., Jeyakani J. and Bourque G. (2013) The majority of primate-specific regulatory sequences are derived from transposable elements. PLOS Genetics 9: e1003504. [PMC free article: PMC3649963] [PubMed: 23675311]
    39.
    Trizzino M. et al. (2017) Transposable elements are the primary source of novelty in primate gene regulation. Genome Research 27: 1623–1633. [PMC free article: PMC5630026] [PubMed: 28855262]
    40.
    Etchegaray E., Naville M., Volff J.-N. and Haftek-Terreau Z. (2021) Transposable element-derived sequences in vertebrate development. Mobile DNA 12: 1. [PMC free article: PMC7786948] [PubMed: 33407840]
    41.
    Cosby R.L. et al. (2021) Recurrent evolution of vertebrate transcription factors by transposase capture. Science 371: eabc6405. [PMC free article: PMC8186458] [PubMed: 33602827]
    42.
    Hermant C. and Torres-Padilla M.-E. (2021) TFs for TEs: The transcription factor repertoire of mammalian transposable elements. Genes & Development 35: 22–39. [PMC free article: PMC7778262] [PubMed: 33397727]
    43.
    Aziz R.K., Breitbart M. and Edwards R.A. (2010) Transposases are the most abundant, most ubiquitous genes in nature. Nucleic Acids Research 38: 4207–4217. [PMC free article: PMC2910039] [PubMed: 20215432]
    44.
    Serrato-Capuchina A. and Matute D.R. (2018) The role of transposable elements in speciation. Genes 9: 254. [PMC free article: PMC5977194] [PubMed: 29762547]
    45.
    Wells J.N. and Feschotte C. (2020) A field guide to eukaryotic transposable elements. Annual Review of Genetics 54: 539–561. [PMC free article: PMC8293684] [PubMed: 32955944]
    46.
    Britten R.J., Baron W.F., Stout D.B. and Davidson E.H. (1988) Sources and evolution of human Alu repeated sequences. Proceedings of the National Academy of Sciences USA 85: 4770–4774. [PMC free article: PMC280517] [PubMed: 3387437]
    47.
    Feschotte C. (2008) Transposable elements and the evolution of regulatory networks. Nature Reviews Genetics 9: 397–405. [PMC free article: PMC2596197] [PubMed: 18368054]
    48.
    Patoori S., Barnada S. and Trizzino M. (2021) Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors. bioRxiv epub: 2021.11.24.469877. [PMC free article: PMC9641669] [PubMed: 36052683]
    49.
    Ohno S. (1972) So much “junk” DNA in our genome. Brookhaven Symposia in Biology 23: 366–370. [PubMed: 5065367]
    50.
    King J.L. and Jukes T.H. (1969) Non-darwinian evolution. Science 164: 788–798. [PubMed: 5767777]
    51.
    Muller H.J. (1950) Our load of mutations. American Journal of Human Genetics 2: 111–176. [PMC free article: PMC1716299] [PubMed: 14771033]
    52.
    Muller H.J. (1964) The relation of recombination to mutational advance. Mutation Research 1: 2–9. [PubMed: 14195748]
    53.
    Ohno S. (1972) An argument for the genetic simplicity of man and other mammals. Journal of Human Evolution 1: 651–662.
    54.
    Haldane J.B.S. (1957) The cost of natural selection. Journal of Genetics 55: 511.
    55.
    Nei M. (1969) Gene duplication and nucleotide substitution in evolution. Nature 221: 40–42. [PubMed: 5782607]
    56.
    Nei M. (2005) Selectionism and neutralism in molecular evolution. Molecular Biology and Evolution 22: 2318–2342. [PMC free article: PMC1513187] [PubMed: 16120807]
    57.
    Eddy S.R. (2012) The C-value paradox, junk DNA and ENCODE. Current Biology 22: R898–9. [PubMed: 23137679]
    58.
    Graur D. (2017) An upper limit on the functional fraction of the human genome. Genome Biology and Evolution 9: 1880–1885. [PMC free article: PMC5570035] [PubMed: 28854598]
    59.
    Charlesworth B., Charlesworth D., Coyne J.A. and Langley C.H. (2016) Hubby and Lewontin on protein variation in natural populations: When molecular genetics came to the rescue of population genetics. Genetics 203: 1497–1503. [PMC free article: PMC4981259] [PubMed: 27516612]
    60.
    Pigliucci M. and Schlichting C.D. (1997) On the limits of quantitative genetics for the study of phenotypic evolution. Acta Biotheoretica 45: 143–160.
    61.
    Paul J. (1972) General theory of chromosome structure and gene activation in Eukaryotes. Nature 238: 444–446. [PubMed: 4561852]
    62.
    Southern E. (1974) Eukaryotic DNA (University Park Press, New York).
    63.
    Freeling M., Xu J., Woodhouse M. and Lisch D. (2015) A solution to the C-Value paradox and the function of junk DNA: The genome balance hypothesis. Molecular Plant 8: 899–910. [PubMed: 25743198]
    64.
    Veitia R.A. and Bottani S. (2009) Whole genome duplications and a ‘function’ for junk DNA? Facts and hypotheses. PLOS ONE 4: e8201. [PMC free article: PMC2788606] [PubMed: 20011530]
    65.
    Brenner S. (1998) Refuge of spandrels. Current Biology 8: R669. [PubMed: 9776723]
    66.
    Brosius J. (2003) How significant is 98.5% ‘junk’ in mammalian genomes? Bioinformatics 19(Suppl 2): ii35.
    67.
    Brosius J. (2003) The contribution of RNAs and retroposition to evolutionary novelties. Genetica 118: 99–116. [PubMed: 12868601]
    68.
    Brosius J. (2005) Waste not, want not - transcript excess in multicellular eukaryotes. Trends in Genetics 21: 287–288. [PubMed: 15851065]
    69.
    Strasser B.J. (2010) Collecting, comparing, and computing sequences: The making of Margaret O. Dayhoff’s Atlas of Protein Sequence and Structure, 1954–1965. Journal of the History of Biology 43: 623–660. [PubMed: 20665074]
    70.
    Cobb M. (2017) 60 years ago, Francis Crick changed the logic of biology. PLOS Biology 15: e2003243. [PMC free article: PMC5602739] [PubMed: 28922352]
    71.
    Zuckerkandl E. and Pauling L. (1962) Molecular evolution, in M. Kasha and B. Pullman (eds.) Horizons in Biochemistry (Academic Press, New York).
    72.
    Margoliash E. (1963) Primary structure and evolution of cytochrome c. Proceedings of the National Academy of Sciences USA 50: 672–679. [PMC free article: PMC221244] [PubMed: 14077496]
    73.
    Dickerson R.E. (1971) The structure of cytochrome c and the rates of molecular evolution. Journal of Molecular Evolution 1: 26–45. [PubMed: 4377446]
    74.
    Kumar S. (2005) Molecular clocks: Four decades of evolution. Nature Reviews Genetics 6: 654–662. [PubMed: 16136655]
    75.
    Ho S.Y.W. and Duchêne S. (2014) Molecular-clock methods for estimating evolutionary rates and timescales. Molecular Ecology 23: 5947–5965. [PubMed: 25290107]
    76.
    Alvarez-Ponce D. (2021) Richard Dickerson, molecular clocks, and rates of protein evolution. Journal of Molecular Evolution 89: 122–126. [PubMed: 33205299]
    77.
    Kimura M. (1968) Evolutionary rate at the molecular level. Nature 217: 624–626. [PubMed: 5637732]
    78.
    Kimura M. (1979) The neutral theory of molecular evolution. Scientific American 241: 98–126. [PubMed: 504979]
    79.
    Kimura M. (1983) The Neutral Theory of Molecular Evolution (Cambridge University Press, New York).
    80.
    Kimura M. (1986) DNA and the neutral theory. Philosophical Transactions of the Royal Society B: Biological Sciences 312: 343–354. [PubMed: 2870526]
    81.
    Kimura M. (1989) The neutral theory of molecular evolution and the world view of the neutralists. Genome 31: 24–31. [PubMed: 2687096]
    82.
    O‘Donald P. (1969) “Haldane’s Dilemma” and the rate of natural selection. Nature 221: 815–816. [PubMed: 5765051]
    83.
    Ohta T. (1973) Slightly deleterious mutant substitutions in evolution. Nature 246: 96–98. [PubMed: 4585855]
    84.
    Ohta T. (2002) Near-neutrality in evolution of genes and gene regulation. Proceedings of the National Academy of Sciences USA 99: 16134–16137. [PMC free article: PMC138577] [PubMed: 12461171]
    85.
    Lynch M. (2002) Intron evolution as a population-genetic process. Proceedings of the National Academy of Sciences USA 99: 6118–6123. [PMC free article: PMC122912] [PubMed: 11983904]
    86.
    Lynch M. and Conery J.S. (2003) The origins of genome complexity. Science 302: 1401–1404. [PubMed: 14631042]
    87.
    Lynch M. (2006) The origins of eukaryotic gene structure. Molecular Biology and Evolution 23: 450–468. [PubMed: 16280547]
    88.
    Lynch M. et al. (2016) Genetic drift, selection and the evolution of the mutation rate. Nature Reviews Genetics 17: 704–714. [PubMed: 27739533]
    89.
    Koonin E.V. (2016) Splendor and misery of adaptation, or the importance of neutral null for understanding evolution. BMC Biology 14: 114. [PMC free article: PMC5180405] [PubMed: 28010725]
    90.
    Sung W., Ackerman M.S., Miller S.F., Doak T.G. and Lynch M. (2012) Drift-barrier hypothesis and mutation-rate evolution. Proceedings of the National Academy of Sciences USA 109: 18488–18492. [PMC free article: PMC3494944] [PubMed: 23077252]
    91.
    Xu C. and Zhang J. (2018) Alternative polyadenylation of mammalian transcripts is generally deleterious, not adaptive. Cell Systems 6: 734–742. [PMC free article: PMC6420822] [PubMed: 29886108]
    92.
    Liu Z. and Zhang J. (2018) Human C-to-U coding RNA editing is largely nonadaptive. Molecular Biology and Evolution 35: 963–969. [PMC free article: PMC6455930] [PubMed: 29385526]
    93.
    Liu Z. and Zhang J. (2018) Most m6A RNA modifications in protein-coding regions are evolutionarily unconserved and likely nonfunctional. Molecular Biology and Evolution 35: 666–675. [PMC free article: PMC5850464] [PubMed: 29228327]
    94.
    Xu C., Park J.-K. and Zhang J. (2019) Evidence that alternative transcriptional initiation is largely nonadaptive. PLOS Biology 17: e3000197. [PMC free article: PMC6438578] [PubMed: 30883542]
    95.
    Xu C. and Zhang J. (2020) A different perspective on alternative cleavage and polyadenylation. Nature Reviews Genetics 21: 63. [PubMed: 31745293]
    96.
    Barton N.H., Etheridge A.M. and Véber A. (2017) The infinitesimal model: Definition, derivation, and implications. Theoretical Population Biology 118: 50–73. [PubMed: 28709925]
    97.
    Hurst L.D. (2009) Genetics and the understanding of selection. Nature Reviews Genetics 10: 83–93. [PubMed: 19119264]
    98.
    Lewontin R.C. (1974) The Genetic Basis of Evolutionary Change (Columbia University Press, New York).
    99.
    Dover G. (2000) How genomic and developmental dynamics affect evolutionary processes. BioEssays 22: 1153–1159. [PubMed: 11084631]
    100.
    Dover G. (2000) Dear Mr Darwin: Letters on the Evolution of Life and Human Nature (Weidenfeld & Nicolson, New York).
    101.
    Mattick J.S., Taft R.J. and Faulkner G.J. (2010) A global view of genomic information--moving beyond the gene and the master regulator. Trends in Genetics 26: 21–28. [PubMed: 19944475]
    102.
    Yusuf L. et al. (2020) Noncoding regions underpin avian bill shape diversification at macroevolutionary scales. Genome Research 30: 553–565. [PMC free article: PMC7197477] [PubMed: 32269134]
    103.
    Gilad Y., Oshlack A., Smyth G.K., Speed T.P. and White K.P. (2006) Expression profiling in primates reveals a rapid evolution of human transcription factors. Nature 440: 242–245. [PubMed: 16525476]
    104.
    Barton R.A. and Venditti C. (2014) Rapid evolution of the cerebellum in humans and other great apes. Current Biology 24: 2440–2444. [PubMed: 25283776]
    105.
    Lou D.I. et al. (2014) Rapid evolution of BRCA1 and BRCA2 in humans and other primates. BMC Evolutionary Biology 14: 155. [PMC free article: PMC4106182] [PubMed: 25011685]
    106.
    Raia P. et al. (2018) Unexpectedly rapid evolution of mandibular shape in hominins. Scientific Reports 8: 7340. [PMC free article: PMC5943523] [PubMed: 29743608]
    107.
    Cechova M. et al. (2020) Dynamic evolution of great ape Y chromosomes. Proceedings of the National Academy of Sciences USA 117: 26273–26280. [PMC free article: PMC7585023] [PubMed: 33020265]
    108.
    Chintalapati M. and Moorjani P. (2020) Evolution of the mutation rate across primates. Current Opinion in Genetics and Development 62: 58–64. [PubMed: 32634682]
    109.
    Bowling D.L. et al. (2020) Rapid evolution of the primate larynx? PLOS Biology 18: e3000764. [PMC free article: PMC7418954] [PubMed: 32780733]
    110.
    Mayr E. (1970) Populations, Species, and Evolution. An Abridgment of Animal Species and Evolution (Harvard University Press, New York).
    111.
    Jacob F. (1977) Evolution and tinkering. Science 196: 1161–1166. [PubMed: 860134]
    112.
    Niklas K.J. (2014) The evolutionary-developmental origins of multicellularity. American Journal of Botany 101: 6–25. [PubMed: 24363320]
    113.
    Ohta T. and Gillespie J.H. (1996) Development of neutral and nearly neutral theories. Theoretical Population Biology 49: 128–142. [PubMed: 8813019]
    114.
    Kreitman M. (1983) Nucleotide polymorphism at the alcohol dehydrogenase locus of Drosophila melanogaster. Nature 304: 412–417. [PubMed: 6410283]
    115.
    Chamary J.V. and Hurst L.D. (2005) Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals. Genome Biology 6: R75. [PMC free article: PMC1242210] [PubMed: 16168082]
    116.
    Chamary J.V., Parmley J.L. and Hurst L.D. (2006) Hearing silence: Non-neutral evolution at synonymous sites in mammals. Nature Reviews Genetics 7: 98–108. [PubMed: 16418745]
    117.
    Lawrie D.S., Messer P.W., Hershberg R. and Petrov D.A. (2013) Strong purifying selection at synonymous sites in D. melanogaster. PLOS Genetics 9: e1003527. [PMC free article: PMC3667748] [PubMed: 23737754]
    118.
    Dhindsa R.S., Copeland B.R., Mustoe A.M. and Goldstein D.B. (2020) Natural selection shapes codon usage in the human genome. American Journal of Human Genetics 107: 83–95. [PMC free article: PMC7332603] [PubMed: 32516569]
    119.
    LaBella A.L., Opulente D.A., Steenwyk J.L., Hittinger C.T. and Rokas A. (2019) Variation and selection on codon usage bias across an entire subphylum. PLOS Genetics 15: e1008304. [PMC free article: PMC6701816] [PubMed: 31365533]
    120.
    Bollenbach T., Vetsigian K. and Kishony R. (2007) Evolution and multilevel optimization of the genetic code. Genome Research 17: 401–404. [PubMed: 17351130]
    121.
    Itzkovitz S. and Alon U. (2007) The genetic code is nearly optimal for allowing additional information within protein-coding sequences. Genome Research 17: 405–412. [PMC free article: PMC1832087] [PubMed: 17293451]
    122.
    Itzkovitz S., Hodis E. and Segal E. (2010) Overlapping codes within protein-coding sequences. Genome Research 20: 1582–1589. [PMC free article: PMC2963821] [PubMed: 20841429]
    123.
    Loehlin D.W., Ames J.R., Vaccaro K. and Carroll S.B. (2019) A major role for noncoding regulatory mutations in the evolution of enzyme activity. Proceedings of the National Academy of Sciences USA 116: 12383–12389. [PMC free article: PMC6589674] [PubMed: 31152141]
    124.
    Siddiq M.A. and Thornton J.W. (2019) Fitness effects but no temperature-mediated balancing selection at the polymorphic Adh gene of Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 116: 21634–21640. [PMC free article: PMC6815130] [PubMed: 31594844]
    125.
    Callier V. (2018) in Quantamagazine, November 8, 2018.
    126.
    Garud N.R., Messer P.W. and Petrov D.A. (2021) Detection of hard and soft selective sweeps from Drosophila melanogaster population genomic data. PLOS Genetics 17: e1009373. [PMC free article: PMC7946363] [PubMed: 33635910]
    127.
    Kern A.D. and Hahn M.W. (2018) The neutral theory in light of natural selection. Molecular Biology and Evolution 35: 1366–1371. [PMC free article: PMC5967545] [PubMed: 29722831]
    128.
    Jensen J.D. et al. (2019) The importance of the Neutral Theory in 1968 and 50 years on: A response to Kern and Hahn 2018. Evolution 73: 111–114. [PMC free article: PMC6496948] [PubMed: 30460993]
    129.
    Pheasant M. and Mattick J.S. (2007) Raising the estimate of functional human sequences. Genome Research 17: 1245–1253. [PubMed: 17690206]
    130.
    Yona A.H., Alm E.J. and Gore J. (2018) Random sequences rapidly evolve into de novo promoters. Nature Communications 9: 1530. [PMC free article: PMC5906472] [PubMed: 29670097]
    131.
    Frith M.C. et al. (2006) Evolutionary turnover of mammalian transcription start sites. Genome Research 16: 713–722. [PMC free article: PMC1473182] [PubMed: 16687732]
    132.
    Ponting C.P. and Hardison R.C. (2011) What fraction of the human genome is functional? Genome Research 21: 1769–1776. [PMC free article: PMC3205562] [PubMed: 21875934]
    133.
    Kutter C. et al. (2012) Rapid turnover of long noncoding RNAs and the evolution of gene expression. PLOS Genetics 8: e1002841. [PMC free article: PMC3406015] [PubMed: 22844254]
    134.
    Quinn J.J. et al. (2016) Rapid evolutionary turnover underlies conserved lncRNA-genome interactions. Genes & Development 30: 191–207. [PMC free article: PMC4719309] [PubMed: 26773003]
    135.
    Glinsky G. and Barakat T.S. (2019) The evolution of Great Apes has shaped the functional enhancers’ landscape in human embryonic stem cells. Stem Cell Research 37: 101456. [PubMed: 31100635]
    136.
    Fisher S., Grice E.A., Vinton R.M., Bessling S.L. and McCallion A.S. (2006) Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science 312: 276–279. [PubMed: 16556802]
    137.
    Carroll S.B. (2008) Evo-devo and an expanding evolutionary synthesis: A genetic theory of morphological evolution. Cell 134: 25–36. [PubMed: 18614008]
    138.
    Carroll S.B., Prud’homme B. and Gompel N (2008) Regulating evolution. Scientific American 298: 60–67. [PubMed: 18444326]
    139.
    Jeong S. et al. (2008) The evolution of gene regulation underlies a morphological difference between two Drosophila sister species. Cell 132: 783–793. [PubMed: 18329365]
    140.
    Shubin N., Tabin C. and Carroll S. (2009) Deep homology and the origins of evolutionary novelty. Nature 457: 818–823. [PubMed: 19212399]
    141.
    Shibata Y. et al. (2012) Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection. PLOS Genetics 8: e1002789. [PMC free article: PMC3386175] [PubMed: 22761590]
    142.
    King M.C. and Wilson A.C. (1975) Evolution at two levels in humans and chimpanzees. Science 188: 107–116. [PubMed: 1090005]
    143.
    Wray G.A. (2007) The evolutionary significance of cis-regulatory mutations. Nature Reviews Genetics 8: 206–216. [PubMed: 17304246]
    144.
    Wolfe K.H., Sharp P.M. and Li W.-H. (1989) Mutation rates differ among regions of the mammalian genome. Nature 337: 283–285. [PubMed: 2911369]
    145.
    Ellegren H., Smith N.G. and Webster M.T. (2003) Mutation rate variation in the mammalian genome. Current Opinion in Genetics and Development 13: 562–568. [PubMed: 14638315]
    146.
    Supek F. and Lehner B. (2015) Differential DNA mismatch repair underlies mutation rate variation across the human genome. Nature 521: 81–84. [PMC free article: PMC4425546] [PubMed: 25707793]
    147.
    Perera D. et al. (2016) Differential DNA repair underlies mutation hotspots at active promoters in cancer genomes. Nature 532: 259–263. [PubMed: 27075100]
    148.
    Oldmeadow C., Mengersen K., Mattick J.S. and Keith J.M. (2010) Multiple evolutionary rate classes in animal genome evolution. Molecular Biology and Evolution 27: 942–953. [PubMed: 19955480]
    149.
    Barriere A., Gordon K.L. and Ruvinsky I. (2011) Distinct functional constraints partition sequence conservation in a cis-regulatory element. PLOS Genetics 7: e1002095. [PMC free article: PMC3107193] [PubMed: 21655084]
    150.
    Pouyet F., Aeschbacher S., Thiéry A. and Excoffier L. (2018) Background selection and biased gene conversion affect more than 95% of the human genome and bias demographic inferences. eLife 7: e36317. [PMC free article: PMC6177262] [PubMed: 30125248]
    151.
    Monroe J.G. et al. (2022) Mutation bias reflects natural selection in Arabidopsis thaliana. Nature 602: 101-5. [PMC free article: PMC8810380] [PubMed: 35022609]
    152.
    Zhang J. (2022) Important genomic regions mutate less often than do other regions. Nature. News & Views: https://doi​.org/10.1038​/d41586-022-00017-6. [PubMed: 35022583]
    153.
    Vierstra J. et al. (2020) Global reference mapping of human transcription factor footprints. Nature 583: 729–736. [PMC free article: PMC7410829] [PubMed: 32728250]
    154.
    Zuckerkandl E. (1976) Gene control in eukaryotes and the c-value paradox “excess” DNA as an impediment to transcription of coding sequences. Journal of Molecular Evolution 9: 73–104. [PubMed: 798041]
    155.
    Doolittle W.F. and Sapienza C. (1980) Selfish genes, the phenotype paradigm and genome evolution. Nature 284: 601–603. [PubMed: 6245369]
    156.
    Comings D.E. (1972) The structure and function of chromatin, in Advances in Human Genetics (Springer). [PubMed: 4578264]
    157.
    Gilbert W. (1978) Why genes in pieces? Nature 271: 501. [PubMed: 622185]
    158.
    Loomis Jr. W.F. (1973) Vestigial DNA? Developmental Biology 30: 3–4. [PubMed: 4703682]
    159.
    Hutchinson J., Narayan R.K.J. and Rees H. (1980) Constraints upon the composition of supplementary DNA. Chromosoma 78: 137–145. [PubMed: 7389509]
    160.
    Jain H.K. (1980) Incidental DNA. Nature 288: 647–648. [PubMed: 7453799]
    161.
    Vanin E.F. (1985) Processed pseudogenes: Characteristics and evolution. Annual Review of Genetics 19: 253–272. [PubMed: 3909943]
    162.
    Jacq C., Miller J.R. and Brownlee G.G. (1977) A pseudogene structure in 5S DNA of Xenopus laevis. Cell 12: 109–120. [PubMed: 561661]
    163.
    Ohno S. (1985) Dispensable genes. Trends in Genetics 1: 160–164.
    164.
    Cheetham S.W., Faulkner G.J. and Dinger M.E. (2020) Overcoming challenges and dogmas to understand the functions of pseudogenes. Nature Reviews Genetics 21: 191–201. [PubMed: 31848477]
    165.
    McCarrey J.R. and Riggs A.D. (1986) Determinator-inhibitor pairs as a mechanism for threshold setting in development: A possible function for pseudogenes. Proceedings of the National Academy of Sciences USA 83: 679–683. [PMC free article: PMC322927] [PubMed: 2418440]
    166.
    Nepveu A. and Marcu K.B. (1986) Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO Journal 5: 2859–2865. [PMC free article: PMC1167235] [PubMed: 3024965]
    167.
    Zhou B.-S., Beidler D.R. and Cheng Y.-C. (1992) Identification of antisense RNA transcripts from a human DNA topoisomerase I pseudogene. Cancer Research 52: 4280–4285. [PubMed: 1339303]
    168.
    Korneev S.A., Park J.H. and O‘Shea M. (1999) Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. Journal of Neuroscience 19: 7711–7720. [PMC free article: PMC6782476] [PubMed: 10479675]
    169.
    Korneev S.A. et al. (2008) Novel noncoding antisense RNA transcribed from human anti-NOS2A locus is differentially regulated during neuronal differentiation of embryonic stem cells. RNA 14: 2030–2037. [PMC free article: PMC2553742] [PubMed: 18820242]
    170.
    Koop B.F., Goodman M., Xu P., Chan K. and Slightom J.L. (1986) Primate η-globin DNA sequences and man’s place among the great apes. Nature 319: 234–238. [PubMed: 3945312]
    171.
    Giannopoulou E. et al. (2012) A single nucleotide polymorphism in the HbbP1 gene in the human β-globin locus is associated with a mild β-thalassemia disease phenotype. Hemoglobin 36: 433–445. [PubMed: 22943111]
    172.
    Moleirinho A. et al. (2013) Evolutionary constraints in the β-globin cluster: The signature of purifying selection at the δ-globin (HBD) locus and its role in developmental gene regulation. Genome Biology and Evolution 5: 559–571. [PMC free article: PMC3622298] [PubMed: 23431002]
    173.
    Ma Y. et al. (2021) Genome-wide analysis of pseudogenes reveals HBBP1′s human-specific essentiality in erythropoiesis and implication in β-thalassemia. Developmental Cell 56: 478–493. [PubMed: 33476555]
    174.
    O‘Brien S.J. (1973) On estimating functional gene number in Eukaryotes. Nature New Biology 242: 52–54. [PubMed: 4512011]
    175.
    Gerdes S.Y. et al. (2003) Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. Journal of Bacteriology 185: 5673–5684. [PMC free article: PMC193955] [PubMed: 13129938]
    176.
    Giaever G. et al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418: 387–391. [PubMed: 12140549]
    177.
    Brown S.W. (1966) Heterochromatin. Science 151: 417–425. [PubMed: 5322971]
    178.
    Peacock W.J. et al. (1978) Fine structure and evolution of DNA in heterochromatin. Cold Spring Harbor Symposia on Quantitative Biology 42: 1121–1135. [PubMed: 98264]
    179.
    Williams G.C. (1966) Adaptation and Natural Selection (Princeton University Press, New York).
    180.
    Hamilton W.D. (1970) Selfish and spiteful behaviour in an evolutionary model. Nature 228: 1218–1220. [PubMed: 4395095]
    181.
    Dawkins R. (1976) The Selfish Gene (Oxford University Press, New York).
    182.
    Orgel L.E. and Crick F.H. (1980) Selfish DNA: The ultimate parasite. Nature 284: 604–607. [PubMed: 7366731]
    183.
    Orgel L.E., Crick F.H. and Sapienza C. (1980) Selfish DNA. Nature 288: 645–646. [PubMed: 7453798]
    184.
    Fedoroff N.V. (2012) McClintock’s challenge in the 21st century. Proceedings of the National Academy of Sciences USA 109: 20200–20203. [PMC free article: PMC3528499] [PubMed: 23150590]
    185.
    Stoye J.P., Fenner S., Greenoak G.E., Moran C. and Coffin J.M. (1988) Role of endogenous retroviruses as mutagens: The hairless mutation of mice. Cell 54: 383–391. [PubMed: 2840205]
    186.
    Kleckner N. (1981) Transposable elements in prokaryotes. Annual Review of Genetics 15: 341–404. [PubMed: 6279020]
    187.
    Shapiro J.A. (1992) Natural genetic engineering in evolution. Genetica 86: 99–111. [PubMed: 1334920]
    188.
    Witzany G. (2009) Natural Genetic Engineering and Natural Genome Editing, Annals of the New York Academy of Sciences, Vol. 1178 (Wiley-Blackwell, New York). [PubMed: 19845624]
    189.
    Charlesworth B., Sniegowski P. and Stephan W. (1994) The evolutionary dynamics of repetitive DNA in eukaryotes. Nature 371: 215–220. [PubMed: 8078581]
    190.
    Iranzo J. and Koonin E.V. (2018) How genetic parasites persist despite the purge of natural selection. Europhysics Letters 122: 58001.
    191.
    Palazzo A.F. and Koonin E.V. (2020) Functional long non-coding RNAs evolve from junk transcripts. Cell 183: 1151–1161. [PubMed: 33068526]
    192.
    Comfort N.C. (2001) From controlling elements to transposons: Barbara McClintock and the Nobel Prize. Trends in Biochemical Sciences 26: 454–457. [PubMed: 11440859]
    193.
    Comfort N.C. (2003) The Tangled Field: Barbara McClintock’s Search for the Patterns of Genetic Control (Harvard University Press, New York).
    194.
    Brandt J. et al. (2005) Transposable elements as a source of genetic innovation: Expression and evolution of a family of retrotransposon-derived neogenes in mammals. Gene 345: 101–111. [PubMed: 15716091]
    195.
    Gall J.G. (1981) Chromosome structure and the C-value paradox. Journal of Cell Biology 91: S3–S14. [PMC free article: PMC2112778] [PubMed: 7033242]
    196.
    Hurst G.D.D. and Werren J.H. (2001) The role of selfish genetic elements in eukaryotic evolution. Nature Reviews Genetics 2: 597–606. [PubMed: 11483984]
    197.
    Williamson B. (1977) DNA insertions and gene structure. Nature 270: 295–297.
    198.
    Darnell Jr. J.E., (2013) Reflections on the history of pre-mRNA processing and highlights of current knowledge: A unified picture. RNA 19: 443–460. [PMC free article: PMC3677254] [PubMed: 23440351]
    199.
    Bachenheimer S. and Darnell J.E. (1975) Adenovirus-2 mRNA is transcribed as part of a high-molecular-weight precursor RNA. Proceedings of the National Academy of Sciences USA 72: 4445–4449. [PMC free article: PMC388738] [PubMed: 1060124]
    200.
    Berget S.M., Moore C. and Sharp P.A. (1977) Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proceedings of the National Academy of Sciences USA 74: 3171–3175. [PMC free article: PMC431482] [PubMed: 269380]
    201.
    Chow L.T., Gelinas R.E., Broker T.R. and Roberts R.J. (1977) An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA. Cell 12: 1–8. [PubMed: 902310]
    202.
    Berk A.J. (2016) Discovery of RNA splicing and genes in pieces. Proceedings of the National Academy of Sciences USA 113: 801–805. [PMC free article: PMC4743779] [PubMed: 26787897]
    203.
    Westphal H. and Lai S.-P. (1978) Displacement loops in adenovirus DNA-RNA hybrids. Cold Spring Harbor Symposia on Quantitative Biology 42: 555–558. [PubMed: 277363]
    204.
    Jeffreys A.J. and Flavell R.A. (1977) Rabbit beta-globin gene contains a large insert in coding sequence. Cell 12: 1097–1108. [PubMed: 597859]
    205.
    Kinniburgh A.J., Mertz J.E. and Ross J. (1978) The precursor of mouse β-globin messenger RNA contains two intervening RNA sequences. Cell 14: 681–693. [PubMed: 688388]
    206.
    Breathnach R., Mandel J.L. and Chambon P. (1977) Ovalbumin gene is split in chicken DNA. Nature 270: 314–319. [PubMed: 593351]
    207.
    Doel M.T., Houghton M., Cook E.A. and Carey N.H. (1977) The presence of ovalbumin mRNA coding sequences in multiple restriction fragments of chicken DNA. Nucleic Acids Research 4: 3701–3713. [PMC free article: PMC343194] [PubMed: 563592]
    208.
    Baldacci P. et al. (1979) Isolation of the lysozyme gene of chicken. Nucleic Acids Research 6: 2667–2681. [PMC free article: PMC327884] [PubMed: 461199]
    209.
    Tonegawa S., Maxam A.M., Tizard R., Bernard O. and Gilbert W. (1978) Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. Proceedings of the National Academy of Sciences USA 75: 1485–1489. [PMC free article: PMC411497] [PubMed: 418414]
    210.
    Glover D.M. and Hogness D.S. (1977) Novel arrangement of 18s and 28s sequences in a repeating unit of Drosophila-melanogaster rDNA. Cell 10: 167–176. [PubMed: 402220]
    211.
    Goldberg S., Weber J. and Darnell J.E. (1977) The definition of a large viral transcription unit late in Ad2 infection of HeLa cells: Mapping by effects of ultraviolet irradiation. Cell 10: 617–621. [PubMed: 862023]
    212.
    Goldberg S., Schwartz H. and Darnell Jr. J.E., (1977) Evidence from UV transcription mapping in HeLa cells that heterogeneous nuclear RNA is the messenger RNA precursor. Proceedings of the National Academy of Sciences USA 74: 4520–4523. [PMC free article: PMC431976] [PubMed: 270700]
    213.
    Konkel D.A., Tilghman S.M. and Leder P. (1978) The sequence of the chromosomal mouse β-globin major gene: Homologies in capping, splicing and poly(A) sites. Cell 15: 1125–1132. [PubMed: 569555]
    214.
    Crick F. (1979) Split genes and RNA splicing. Science 204: 264–271. [PubMed: 373120]
    215.
    Sharp P.A. (2005) The discovery of split genes and RNA splicing. Trends in Biochemical Sciences 30: 279–281. [PubMed: 15950867]
    216.
    Cavalier-Smith T. (1985) Selfish DNA and the origin of introns. Nature 315: 283–284. [PubMed: 2987701]
    217.
    Mattick J.S. (1994) Introns: Evolution and function. Current Opinion in Genetics and Development 4: 823–831. [PubMed: 7888751]
    218.
    Gallegos J.E. and Rose A.B. (2015) The enduring mystery of intron-mediated enhancement. Plant Science 237: 8–15. [PubMed: 26089147]
    219.
    Darnell J.E. (2002) The surprises of mammalian molecular cell biology. Nature Medicine 8: 1068–1071. [PubMed: 12357235]
    220.
    Ohno S. (1980) Gene duplication, junk DNA, intervening sequences and the universal signal for their removal. Revista Brasileira De Genetica 3: 99–114.
    221.
    Milcarek C., Price R. and Penman S. (1974) The metabolism of a poly(A) minus mRNA fraction in HeLa cells. Cell 3: 1–10. [PubMed: 4213457]
    222.
    Salditt-Georgieff M., Harpold M.M., Wilson M.C. and Darnell Jr. J.E., (1981) Large heterogeneous nuclear ribonucleic acid has three times as many 5′ caps as polyadenylic acid segments, and most caps do not enter polyribosomes. Molecular Cell Biology 1: 179–187. [PMC free article: PMC369657] [PubMed: 6152852]
    223.
    Cheng J. et al. (2005) Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308: 1149–1154. [PubMed: 15790807]
    224.
    Padgett R.A., Grabowski P.J., Konarska M.M., Seiler S. and Sharp P.A. (1986) Splicing of messenger RNA precursors. Annual Review of Biochemistry 55: 1119–1150. [PubMed: 2943217]
    225.
    Sharp P.A. et al. (1987) Splicing of messenger RNA precursors. Cold Spring Harbor Symposia on Quantitative Biology 52: 277–285. [PubMed: 3331341]
    226.
    Xing Y., Johnson C.V., Dobner P.R. and Lawrence J.B. (1993) Higher level organization of individual gene transcription and RNA splicing. Science 259: 1326–1330. [PubMed: 8446901]
    227.
    St Laurent G. et al. (2012) Intronic RNAs constitute the major fraction of the non-coding RNA in mammalian cells. BMC Genomics 13: 504. [PMC free article: PMC3507791] [PubMed: 23006825]
    228.
    Heilig R., Mursaskowsky R., Kloepfer C. and Mandel J.L. (1982) The ovalbumin gene family: Complete sequence and structure of the Y gene. Nucleic Acids Research 10: 4363–4382. [PMC free article: PMC320805] [PubMed: 7122240]
    229.
    Leff S.E., Rosenfeld M.G. and Evans R.M. (1986) Complex transcriptional units: Diversity in gene expression by alternative RNA processing. Annual Review of Biochemistry 55: 1091–1117. [PubMed: 3017190]
    230.
    Croft L. et al. (2000) ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome. Nature Genetics 24: 340–341. [PubMed: 10742092]
    231.
    Lareau L.F., Green R.E., Bhatnagar R.S. and Brenner S.E. (2004) The evolving roles of alternative splicing. Current Opinion in Structural Biology 14: 273–282. [PubMed: 15193306]
    232.
    Blencowe B.J. (2006) Alternative splicing: New insights from global analyses. Cell 126: 37–47. [PubMed: 16839875]
    233.
    Darnell Jr. J.E., (1978) Implications of RNA-RNA splicing in evolution of eukaryotic cells. Science 202: 1257–1260. [PubMed: 364651]
    234.
    Doolittle W.F. (1978) Genes in pieces - were they ever together. Nature 272: 581–582.
    235.
    Blake C.C.F. (1978) Do genes-in-pieces imply proteins-in-pieces? Nature 273: 267.
    236.
    Blake C.C. (1979) Exons encode protein functional units. Nature 277: 598. [PubMed: 423957]
    237.
    Blake C.C. (1981) Exons and the structure, function and evolution of haemoglobin. Nature 291: 616. [PubMed: 7242670]
    238.
    Holland S.K. and Blake C.C. (1987) Proteins, exons and molecular evolution. Biosystems 20: 181–206. [PubMed: 3038209]
    239.
    Stoltzfus A., Spencer D.F., Zuker M., Logsdon Jr. J.M., and Doolittle W.F. (1994) Testing the exon theory of genes: The evidence from protein structure. Science 265: 202–207. [PubMed: 8023140]
    240.
    Deveson I.W. et al. (2018) Universal alternative splicing of noncoding exons. Cell Systems 6: 245–255. [PubMed: 29396323]
    241.
    Palmer J.D. and Logsdon Jr. J.M., (1991) The recent origins of introns. Current Opinion in Genetics and Development 1: 470–477. [PubMed: 1822279]
    242.
    Cavalier-Smith T. (1985) Eukaryotic gene numbers, non-coding DNA and genome size, inT. Cavalier-Smith, (ed.) The Evolution of Genome Size (John Wiley & Sons, New York).
    243.
    Gilbert W., Marchionni M. and McKnight G. (1986) On the antiquity of introns. Cell 46: 151–154. [PubMed: 2424613]
    244.
    Brenner S., Dove W., Herskowitz I. and Thomas R. (1990) Genes and development: Molecular and logical themes. Genetics 126: 479–486. [PMC free article: PMC1204205] [PubMed: 2249752]
    245.
    Ferat J.L. and Michel F.(1993) Group II self-splicing introns in bacteria. Nature 364: 358–361. [PubMed: 7687328]
    246.
    Lambowitz A.M. and Belfort M. (1993) Introns as mobile genetic elements. Annual Review of Biochemistry 62: 587–622. [PubMed: 8352597]
    247.
    Cavalier-Smith T. (1991) Intron phylogeny: A new hypothesis. Trends in Genetics 7: 145–148. [PubMed: 2068786]
    248.
    Logsdon J.M.J. (1998) The recent origins of spliceosomal introns revisited. Current Opinion in Genetics and Development 8: 637–648. [PubMed: 9914210]
    249.
    Ng S.Y. et al. (1985) Evolution of the functional human beta-actin gene and its multi-pseudogene family: Conservation of noncoding regions and chromosomal dispersion of pseudogenes. Molecular and Cellular Biology 5: 2720–2732. [PMC free article: PMC367010] [PubMed: 3837182]
    250.
    Lloyd C. and Gunning P. (1993) Noncoding regions of the gamma-actin gene influence the impact of the gene on myoblast morphology. Journal of Cell Biology 121: 73–82. [PMC free article: PMC2119773] [PubMed: 8458874]
    251.
    Dutton J.R. et al. (2008) An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10. BMC Developmental Biology 8: 105. [PMC free article: PMC2601039] [PubMed: 18950534]
    252.
    Hsu A.P. et al. (2013) GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome. Blood 121: 3830–3837. [PMC free article: PMC3650705] [PubMed: 23502222]
    253.
    Ridley M. (1999) Genome: The Autobiography of a Species in 23 Chapters (HarperCollins, New York).
    254.
    Sharp P.A. (1985) On the origin of RNA splicing and introns. Cell 42: 397–400. [PubMed: 2411416]
    255.
    Bridgeman B. (1995) A review of the role of efference copy in sensory and oculomotor control systems. Annals of Biomedical Engineering 23: 409–422. [PubMed: 7486348]
    256.
    Mattick J.S. and Gagen M.J. (2001) The evolution of controlled multitasked gene networks: The role of introns and other noncoding RNAs in the development of complex organisms. Molecular Biology and Evolution 18: 1611–1630. [PubMed: 11504843]
    257.
    Mattick J.S. (2001) Non-coding RNAs: The architects of eukaryotic complexity. EMBO Reports 2: 986–991. [PMC free article: PMC1084129] [PubMed: 11713189]
    258.
    Mattick J.S. (2003) Challenging the dogma: The hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 25: 930–939. [PubMed: 14505360]
    259.
    Mattick J.S. (2004) RNA regulation: A new genetics? Nature Reviews Genetics 5: 316–323. [PubMed: 15131654]
    260.
    Mattick J.S. (2004) The hidden genetic program of complex organisms. Scientific American 291: 60–67. [PubMed: 15487671]
    261.
    Mattick J.S. (2007) A new paradigm for developmental biology. Journal of Experimental Biology 210: 1526–1547. [PubMed: 17449818]
    262.
    Amaral P.P., Dinger M.E., Mercer T.R. and Mattick J.S. (2008) The eukaryotic genome as an RNA machine. Science 319: 1787–1789. [PubMed: 18369136]
    263.
    Amaral P.P. and Mattick J.S. (2008) Noncoding RNA in development. Mammalian Genome 19: 454–492. [PubMed: 18839252]
    264.
    Mattick J.S. (2009) Deconstructing the dogma: A new view of the evolution and genetic programming of complex organisms. Annals of the New York Academy of Science 1178: 29–46. [PubMed: 19845626]
    265.
    Mattick J.S. (2011) The central role of RNA in human development and cognition. FEBS Letters 585: 1600–1616. [PubMed: 21557942]
    266.
    Morris K.V. and Mattick J.S. (2014) The rise of regulatory RNA. Nature Reviews Genetics 15: 423–437. [PMC free article: PMC4314111] [PubMed: 24776770]
    267.
    Borsari B. et al. (2021) Enhancers with tissue-specific activity are enriched in intronic regions. Genome Research 31: 1325–1336. [PMC free article: PMC8327915] [PubMed: 34290042]
    268.
    Lin S.L., Kim H. and Ying S.Y. (2008) Intron-mediated RNA interference and microRNA (miRNA). Frontiers in Bioscience 13: 2216–2230. [PubMed: 17981704]

    Chapter 8

    1.
    Chomczynski P. and Sacchi N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry 162: 156–159. [PubMed: 2440339]
    2.
    Moriyama Y., Hodnett J.L., Prestayko A.W. and Busch H. (1969) Studies on the nuclear 4 to 7S RNA of the Novikoff hepatoma. Journal of Molecular Biology 39: 335–349. [PubMed: 4312042]
    3.
    Bishop J.M. et al. (1970) The low molecular weight RNAs of Rous sarcoma virus. II. The 7S RNA. Virology 42: 927–937. [PubMed: 4321311]
    4.
    Prestayko A.W. and Busch H. (1968) Low molecular weight RNA of the chromatin fraction from Novikoff hepatoma and rat liver nuclei. Biochimica et Biophysica Acta 169: 327–337. [PubMed: 4302868]
    5.
    Nakamura T., Prestayko A.W. and Busch H. (1968) Studies on nucleolar 4 to 6S ribonucleic acid of Novikoff hepatoma cells. Journal of Biological Chemistry 243: 1368–1375. [PubMed: 4296684]
    6.
    Weinberg R.A. and Penman S. (1968) Small molecular weight monodisperse nuclear RNA. Journal of Molecular Biology 38: 289–304. [PubMed: 5718554]
    7.
    Dingman C.W. and Peacock A.C. (1968) Analytical studies on nuclear ribonucleic acid using polyacrylamide gel electrophoresis. Biochemistry 7: 659–668. [PubMed: 5644137]
    8.
    Prestayko A.W., Tonato M. and Busch H. (1970) Low molecular weight RNA associated with 28S nucleolar RNA. Journal of Molecular Biology 47: 505–515. [PubMed: 5418169]
    9.
    Pederson T. and Bhorjee J.S. (1979) Evidence for a role of RNA in eukaryotic chromosome structure. Metabolically stable, small nuclear RNA species are covalently linked to chromosomal DNA in HeLa cells. Journal of Molecular Biology 128: 451–480. [PubMed: 571474]
    10.
    Weinberg R.A. (1973) Nuclear RNA metabolism. Annual Review of Biochemistry 42: 329–354. [PubMed: 4581227]
    11.
    Zieve G., Benecke B.J. and Penman S. (1977) Synthesis of two classes of small RNA species in vivo and in vitro. Biochemistry 16: 4520–4525. [PubMed: 911771]
    12.
    Reichel R. and Benecke B.J. (1980) Reinitiation of synthesis of small cytoplasmic RNA species K and L in isolated HeLa cell nuclei in vitro. Nucleic Acids Research 8: 225–234. [PMC free article: PMC327263] [PubMed: 7422543]
    13.
    Elder J.T., Pan J., Duncan C.H. and Weissman S.M. (1981) Transcriptional analysis of interspersed repetitive polymerase III transcription units in human DNA. Nucleic Acids Research 9: 1171–1189. [PMC free article: PMC326744] [PubMed: 7232214]
    14.
    Haynes S.R. and Jelinek W.R. (1981) Low molecular weight RNAs transcribed in vitro by RNA polymerase III from Alu-type dispersed repeats in Chinese hamster DNA are also found in vivo. Proceedings of the National Academy of Sciences USA 78: 6130–6134. [PMC free article: PMC348991] [PubMed: 6796957]
    15.
    Lerner M.R. and Steitz J.A. (1979) Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proceedings of the National Academy of Sciences USA 76: 5495–5499. [PMC free article: PMC411675] [PubMed: 316537]
    16.
    Lerner M.R., Boyle J.A., Mount S.M., Wolin S.L. and Steitz J.A. (1980) Are snRNPs involved in splicing? Nature 283: 220–224. [PubMed: 7350545]
    17.
    Rogers J. and Wall R. (1980) A mechanism for RNA splicing. Proceedings of the National Academy of Sciences USA 77: 1877–1879. [PMC free article: PMC348611] [PubMed: 6246511]
    18.
    Shine J. and Dalgarno L. (1975) Determinant of cistron specificity in bacterial ribosomes. Nature 254: 34–38. [PubMed: 803646]
    19.
    Steitz J.A. and Jakes K. (1975) How ribosomes select initiator regions in mRNA: Base pair formation between the 3′ terminus of 16S rRNA and the mRNA during initiation of protein synthesis in Escherichia coli. Proceedings of the National Academy of Sciences USA 72: 4734–4738. [PMC free article: PMC388805] [PubMed: 1107998]
    20.
    Tan E.M. and Kunkel H.G. (1966) Characteristics of a soluble nuclear antigen precipitating with sera of patients with Systemic Lupus Erythematosus. Journal of Immunology 96: 464–471. [PubMed: 5932578]
    21.
    Lerner M.R., Boyle J.A., Hardin J.A. and Steitz J.A. (1981) Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science 211: 400–402. [PubMed: 6164096]
    22.
    Hardin J.A. et al. (1982) Antibodies from patients with connective tissue diseases bind specific subsets of cellular RNA-protein particles. Journal of Clinical investigation 70: 141–147. [PMC free article: PMC370236] [PubMed: 6806318]
    23.
    Reeves W.H., Narain S. and Satoh M. (2003) Henry Kunkel, Stephanie Smith, clinical immunology, and split genes. Lupus 12: 213–217. [PubMed: 12708785]
    24.
    Thore S., Mayer C., Sauter C., Weeks S. and Suck D. (2003) Crystal structures of the Pyrococcus abyssi Sm core and its complex with RNA: Common features of RNA binding in archaea and eukarya. Journal of Biological Chemistry 278: 1239–1247. [PubMed: 12409299]
    25.
    Padgett R.A. (2001) mRNA Splicing: Role of snRNAs (John Wiley & Sons, Ltd, New York).
    26.
    Yang V.W., Lerner M.R., Steitz J.A. and Flint S.J. (1981) A small nuclear ribonucleoprotein is required for splicing of adenoviral early RNA sequences. Proceedings of the National Academy of Sciences USA 78: 1371–1375. [PMC free article: PMC319132] [PubMed: 6940164]
    27.
    Padgett R.A., Mount S.M., Steitz J.A. and Sharp P.A. (1983) Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein. Cell 35: 101–107. [PubMed: 6194895]
    28.
    Calvet J.P. and Pederson T. (1981) Base-pairing interactions between small nuclear RNAs and nuclear RNA precursors as revealed by psoralen cross-linking in vivo. Cell 26: 363–370. [PubMed: 6173132]
    29.
    Calvet J.P., Meyer L.M. and Pederson T. (1982) Small nuclear RNA U2 is base-paired to heterogeneous nuclear RNA. Science 217: 456–458. [PubMed: 6178162]
    30.
    Padgett R.A., Grabowski P.J., Konarska M.M., Seiler S. and Sharp P.A. (1986) Splicing of messenger RNA precursors. Annual Review of Biochemistry 55: 1119–1150. [PubMed: 2943217]
    31.
    Fica S.M. and Nagai K. (2017) Cryo-electron microscopy snapshots of the spliceosome: Structural insights into a dynamic ribonucleoprotein machine. Nature Structural & Molecular Biology 24: 791–799. [PMC free article: PMC6386135] [PubMed: 28981077]
    32.
    Wilkinson M.E., Charenton C. and Nagai K. (2020) RNA splicing by the spliceosome. Annual Review of Biochemistry 89: 359–388. [PubMed: 31794245]
    33.
    Bai R. et al. (2021) Structure of the activated human minor spliceosome. Science 371: eabg0879. [PubMed: 33509932]
    34.
    Kwek K.Y. et al. (2002) U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nature Structural Biology 9: 800–805. [PubMed: 12389039]
    35.
    Jobert L. et al. (2009) Human U1 snRNA forms a new chromatin-associated snRNP with TAF15. EMBO Reports 10: 494–500. [PMC free article: PMC2680868] [PubMed: 19282884]
    36.
    Mondal T., Rasmussen M., Pandey G.K., Isaksson A. and Kanduri C. (2010) Characterization of the RNA content of chromatin. Genome Research 20: 899–907. [PMC free article: PMC2892091] [PubMed: 20404130]
    37.
    Chinen M., Morita M., Fukumura K. and Tani T. (2010) Involvement of the spliceosomal U4 small nuclear RNA in heterochromatic gene silencing at fission yeast centromeres. Journal of Biological Chemistry 285: 5630–5638. [PMC free article: PMC2820790] [PubMed: 20018856]
    38.
    Kaida D. et al. (2010) U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation. Nature 468: 664–668. [PMC free article: PMC2996489] [PubMed: 20881964]
    39.
    Berg M.G. et al. (2012) U1 snRNP determines mRNA length and regulates isoform expression. Cell 150: 53–64. [PMC free article: PMC3412174] [PubMed: 22770214]
    40.
    Yin Y. et al. (2020) U1 snRNP regulates chromatin retention of noncoding RNAs. Nature 580: 147–150. [PubMed: 32238924]
    41.
    Caizzi L. et al. (2021) Efficient RNA polymerase II pause release requires U2 snRNP function. Molecular Cell 81: 1920–1934. [PubMed: 33689748]
    42.
    Hall S.L. and Padgett R.A. (1994) Conserved sequences in a class of rare eukaryotic nuclear introns with non-consensus splice sites. Journal of Molecular Biology 239: 357–365. [PubMed: 8201617]
    43.
    Tarn W.-Y. and Steitz J.A. (1996) A novel spliceosome containing U11, U12, and U5 snRNPs excises a minor class (AT–AC) intron in vitro. Cell 84: 801–811. [PubMed: 8625417]
    44.
    Burge C.B., Padgett R.A. and Sharp P.A. (1998) Evolutionary fates and origins of U12-type introns. Molecular Cell 2: 773–785. [PubMed: 9885565]
    45.
    Turunen J.J., Niemelä E.H., Verma B. and Frilander M.J. (2013) The significant other: Splicing by the minor spliceosome. Wiley Interdisciplinary Reviews RNA 4: 61–76. [PMC free article: PMC3584512] [PubMed: 23074130]
    46.
    Jutzi D., Akinyi M.V., Mechtersheimer J., Frilander M.J. and Ruepp M.-D. (2018) The emerging role of minor intron splicing in neurological disorders. Cell Stress 2: 40–54. [PMC free article: PMC6558932] [PubMed: 31225466]
    47.
    Baumgartner M. et al. (2018) Minor spliceosome inactivation causes microcephaly, owing to cell cycle defects and death of self-amplifying radial glial cells. Development 145: dev166322. [PMC free article: PMC6141777] [PubMed: 30093551]
    48.
    Li L. et al. (2020) Defective minor spliceosomes induce SMA-associated phenotypes through sensitive intron-containing neural genes in Drosophila. Nature Communications 11: 5608. [PMC free article: PMC7644725] [PubMed: 33154379]
    49.
    Pene J.J., Knight Jr. E., and Darnell Jr. J.E. (1968) Characterization of a new low molecular weight RNA in HeLa cell ribosomes. Journal of Molecular Biology 33: 609–623. [PubMed: 5700415]
    50.
    Bachellerie J.P., Michot B. and Raynal F. (1983) Recognition signals for mouse pre-rRNA processing. A potential role for U3 nucleolar RNA. Molecular Biology Reports 9: 79–86. [PubMed: 6193412]
    51.
    Kiss T. (2002) Small nucleolar RNAs: An abundant group of noncoding RNAs with diverse cellular functions. Cell 109: 145–148. [PubMed: 12007400]
    52.
    Rimer J.M. et al. (2018) Long-range function of secreted small nucleolar RNAs that direct 2′-O-methylation. Journal of Biological Chemistry 293: 13284–13296. [PMC free article: PMC6109910] [PubMed: 29980600]
    53.
    Ochs R.L., Lischwe M.A., Spohn W.H. and Busch H. (1985) Fibrillarin: A new protein of the nucleolus identified by autoimmune sera. Biology of the Cell 54: 123–133. [PubMed: 2933102]
    54.
    Tyc K. and Steitz J.A. (1989) U3, U8 and U13 comprise a new class of mammalian snRNPs localized in the cell nucleolus. EMBO Journal 8: 3113–3119. [PMC free article: PMC401391] [PubMed: 2531075]
    55.
    Fatica A., Galardi S., Altieri F. and Bozzoni I. (2000) Fibrillarin binds directly and specifically to U16 box C/D snoRNA. RNA 6: 88–95. [PMC free article: PMC1369896] [PubMed: 10668801]
    56.
    Kass S., Tyc K., Steitz J.A. and Sollner-Webb B. (1990) The U3 small nucleolar ribonucleoprotein functions in the first step of preribosomal RNA processing. Cell 60: 897–908. [PubMed: 2156625]
    57.
    Kiss-Laszlo Z., Henry Y., Bachellerie J.P., Caizergues-Ferrer M. and Kiss T. (1996) Site-specific ribose methylation of preribosomal RNA: A novel function for small nucleolar RNAs. Cell 85: 1077–1088. [PubMed: 8674114]
    58.
    Tollervey D. and Kiss T. (1997) Function and synthesis of small nucleolar RNAs. Current Opinion in Cell Biology 9: 337–342. [PubMed: 9159079]
    59.
    Fournier M.J. and Maxwell E.S. (1993) The nucleolar snRNAs: Catching up with the spliceosomal snRNAs. Trends in Biochemical Sciences 18: 131–135. [PubMed: 8493724]
    60.
    Bachellerie J.P., Cavaille J. and Huttenhofer A. (2002) The expanding snoRNA world. Biochimie 84: 775–790. [PubMed: 12457565]
    61.
    Lafontaine D.L.J. and Tollervey D. (1998) Birth of the snoRNPs: The evolution of the modification-guide snoRNAs. Trends in Biochemical Sciences 23: 383–388. [PubMed: 9810226]
    62.
    Omer A.D. et al. (2000) Homologs of small nucleolar RNAs in Archaea. Science 288: 517–522. [PubMed: 10775111]
    63.
    Terns M.P. and Terns R.M. (2002) Small nucleolar RNAs: Versatile trans-acting molecules of ancient evolutionary origin. Gene Expression 10: 17–39. [PMC free article: PMC5977530] [PubMed: 11868985]
    64.
    Abel Y. and Rederstorff M. (2019) SnoRNAs and the emerging class of sdRNAs: Multifaceted players in oncogenesis. Biochimie 164: 17–21. [PubMed: 31078583]
    65.
    Venema J. and Tollervey D. (1999) Ribosome synthesis in Saccharomyces cerevisiae. Annual Review of Genetics 33: 261–311. [PubMed: 10690410]
    66.
    Falaleeva M. et al. (2016) Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing. Proceedings of the National Academy of Sciences USA 113: E1625–34. [PMC free article: PMC4812717] [PubMed: 26957605]
    67.
    Sharma S. et al. (2017) Specialized box C/D snoRNPs act as antisense guides to target RNA base acetylation. PLOS Genetics 13: e1006804. [PMC free article: PMC5464676] [PubMed: 28542199]
    68.
    Gall J.G., Bellini M., Wu Z. and Murphy C. (1999) Assembly of the nuclear transcription and processing machinery: Cajal bodies (coiled bodies) and transcriptosomes. Molecular Biology of the Cell 10: 4385–4402. [PMC free article: PMC25765] [PubMed: 10588665]
    69.
    Jády B.E. and Kiss T. (2001) A small nucleolar guide RNA functions both in 2′-O-ribose methylation and pseudouridylation of the U5 spliceosomal RNA. EMBO Journal 20: 541–551. [PMC free article: PMC133463] [PubMed: 11157760]
    70.
    Mowry K.L. and Steitz J.A. (1987) Identification of the human U7 snRNP as one of several factors involved in the 3′ end maturation of histone premessenger RNA’s. Science 238: 1682–1687. [PubMed: 2825355]
    71.
    Gall J.G. and Callan H.G. (1989) The sphere organelle contains small nuclear ribonucleoproteins. Proceedings of the National Academy of Sciences USA 86: 6635–6639. [PMC free article: PMC297899] [PubMed: 2528145]
    72.
    Bratkovič T., Božič J. and Rogelj B. (2019) Functional diversity of small nucleolar RNAs. Nucleic Acids Research 48: 1627–1651. [PMC free article: PMC7038934] [PubMed: 31828325]
    73.
    Vitali P. and Kiss T. (2019) Cooperative 2′-O-methylation of the wobble cytidine of human elongator tRNAMet(CAT) by a nucleolar and a Cajal body-specific box C/D RNP. Genes & Development 33: 741–746. [PMC free article: PMC6601510] [PubMed: 31171702]
    74.
    Nostramo R.T. and Hopper A.K. (2019) Beyond rRNA and snRNA: tRNA as a 2′-O-methylation target for nucleolar and Cajal body box C/D RNPs. Genes & Development 33: 739–740. [PMC free article: PMC6601515] [PubMed: 31262844]
    75.
    Mitchell J.R., Cheng J. and Collins K. (1999) A box H/ACA small nucleolar RNA-like domain at the human telomerase RNA 3′ end. Molecular and Cellular Biology 19: 567–576. [PMC free article: PMC83914] [PubMed: 9858580]
    76.
    Jady B.E., Bertrand E. and Kiss T. (2004) Human telomerase RNA and box H/ACA scaRNAs share a common Cajal body-specific localization signal. Journal of Cell Biology 164: 647–652. [PMC free article: PMC2172171] [PubMed: 14981093]
    77.
    Ghanim G.E. et al. (2021) Structure of human telomerase holoenzyme with bound telomeric DNA. Nature 593: 449–453. [PMC free article: PMC7610991] [PubMed: 33883742]
    78.
    Jády B.E., Ketele A. and Kiss T. (2012) Human intron-encoded Alu RNAs are processed and packaged into Wdr79-associated nucleoplasmic box H/ACA RNPs. Genes & Development 26: 1897–1910. [PMC free article: PMC3435494] [PubMed: 22892240]
    79.
    Schubert T. et al. (2012) Df31 protein and snoRNAs maintain accessible higher-order structures of chromatin. Molecular Cell 48: 434–444. [PubMed: 23022379]
    80.
    Jorjani H. et al. (2016) An updated human snoRNAome. Nucleic Acids Research 44: 5068–5082. [PMC free article: PMC4914119] [PubMed: 27174936]
    81.
    Kufel J. and Grzechnik P. (2019) Small nucleolar RNAs tell a different tale. Trends in Genetics 35: 104–117. [PubMed: 30563726]
    82.
    Maxwell E.S. and Fournier M.J. (1995) The small nucleolar RNAs. Annual Review of Biochemistry 64: 897–934. [PubMed: 7574504]
    83.
    Tycowski K.T., Shu M.D. and Steitz J.A. (1996) A mammalian gene with introns instead of exons generating stable RNA products. Nature 379: 464–466. [PubMed: 8559254]
    84.
    Bortolin M.L. and Kiss T. (1998) Human U19 intron-encoded snoRNA is processed from a long primary transcript that possesses little potential for protein coding. RNA 4: 445–454. [PMC free article: PMC1369630] [PubMed: 9630250]
    85.
    Pelczar P. and Filipowicz W. (1998) The host gene for intronic U17 small nucleolar RNAs in mammals has no protein-coding potential and is a member of the 5′-terminal oligopyrimidine gene family. Molecular and Cellular Biology 18: 4509–4518. [PMC free article: PMC109036] [PubMed: 9671460]
    86.
    Rebane A., Tamme R., Laan M., Pata I. and Metspalu A. (1998) A novel snoRNA (U73) is encoded within the introns of the human and mouse ribosomal protein S3a genes. Gene 210: 255–263. [PubMed: 9573378]
    87.
    Tanaka R. et al. (2000) Intronic U50 small-nucleolar-RNA (snoRNA) host gene of no protein-coding potential is mapped at the chromosome breakpoint t(3;6)(q27;q15) of human B-cell lymphoma. Genes to Cells 5: 277–287. [PubMed: 10792466]
    88.
    Cavaille J., Seitz H., Paulsen M., Ferguson-Smith A.C. and Bachellerie J.P. (2002) Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region. Human Molecular Genetics 11: 1527–1538. [PubMed: 12045206]
    89.
    Zhang X.-O. et al. (2014) Species-specific alternative splicing leads to unique expression of sno-lncRNAs. BMC Genomics 15: 287. [PMC free article: PMC4234469] [PubMed: 24734784]
    90.
    Smith C.M. and Steitz J.A. (1998) Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5′-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Molecular and Cellular Biology 18: 6897–6909. [PMC free article: PMC109273] [PubMed: 9819378]
    91.
    Cavaille J. et al. (2000) Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proceedings of the National Academy of Sciences USA 97: 14311–14316. [PMC free article: PMC18915] [PubMed: 11106375]
    92.
    Cavaille J., Vitali P., Basyuk E., Huttenhofer A. and Bachellerie J.P. (2001) A novel brain-specific box C/D small nucleolar RNA processed from tandemly repeated introns of a noncoding RNA gene in rats. Journal of Biological Chemistry 276: 26374–26383. [PubMed: 11346658]
    93.
    Lee S., Walker C.L. and Wevrick R. (2003) Prader-Willi syndrome transcripts are expressed in phenotypically significant regions of the developing mouse brain. Gene Expression Patterns 3: 599–609. [PubMed: 12971993]
    94.
    Kawaji H. et al. (2008) Hidden layers of human small RNAs. BMC Genomics 9: 157. [PMC free article: PMC2359750] [PubMed: 18402656]
    95.
    Taft R.J. et al. (2009) Small RNAs derived from snoRNAs. RNA 15: 1233–1240. [PMC free article: PMC2704076] [PubMed: 19474147]
    96.
    Ender C. et al. (2008) A human snoRNA with microRNA-like functions. Molecular Cell 32: 519–528. [PubMed: 19026782]
    97.
    Yin Q.-F. et al. (2012) Long noncoding RNAs with snoRNA ends. Molecular Cell 48: 219–230. [PubMed: 22959273]
    98.
    Xing Y.-H. et al. (2017) SLERT regulates DDX21 rings associated with Pol I transcription. Cell 169: 664 –78. [PubMed: 28475895]
    99.
    Wu M. et al. (2021) lncRNA SLERT controls phase separation of FC/DFCs to facilitate Pol I transcription. Science 373: 547–555. [PubMed: 34326237]
    100.
    Talross G.J.S., Deryusheva S. and Gall J.G. (2021) Stable lariats bearing a snoRNA (slb-snoRNA) in eukaryotic cells: A level of regulation for guide RNAs. Proceedings of the National Academy of Sciences USA 118: e2114156118. [PMC free article: PMC8609340] [PubMed: 34725166]
    101.
    Runte M. et al. (2001) The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A. Human Molecular Genetics 10: 2687–2700. [PubMed: 11726556]
    102.
    Gallagher R.C., Pils B., Albalwi M. and Francke U. (2002) Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader-Willi syndrome. American Journal of Human Genetics 71: 669–678. [PMC free article: PMC379204] [PubMed: 12154412]
    103.
    Kishore S. and Stamm S. (2006) The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 311: 230–232. [PubMed: 16357227]
    104.
    Zieve G. and Penman S. (1976) Small RNA species of the HeLa cell: Metabolism and subcellular localization. Cell 8: 19–31. [PubMed: 954090]
    105.
    Erikson E., Erikson R.L., Henry B. and Pace N.R. (1973) Comparison of oligonucleotides produced by RNase T1 digestion of 7S RNA from avian and murine oncornaviruses and from uninfected cells. Virology 53: 40–46. [PubMed: 4350418]
    106.
    Walter P. and Blobel G. (1982) Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum. Nature 299: 691–698. [PubMed: 6181418]
    107.
    Matlin K.S. (2013) History of the signal hypothesis, in eLS (John Wiley & Sons). 10​.1002/9780470015902.a0025089.
    108.
    Li W.Y., Reddy R., Henning D., Epstein P. and Busch H. (1982) Nucleotide sequence of 7S RNA. Homology to Alu DNA and La 4.5S RNA. Journal of Biological Chemistry 257: 5136–5142. [PubMed: 6802847]
    109.
    Batey R.T., Rambo R.P., Lucast L., Rha B. and Doudna J.A. (2000) Crystal structure of the ribonucleoprotein core of the signal recognition particle. Science 287: 1232–1239. [PubMed: 10678824]
    110.
    Walter P. and Blobel G. (1983) Disassembly and reconstitution of signal recognition particle. Cell 34: 525–533. [PubMed: 6413076]
    111.
    Larsen N. and Zwieb C. (1991) SRP-RNA sequence alignment and secondary structure. Nucleic Acids Research 19: 209–215. [PMC free article: PMC333582] [PubMed: 1707519]
    112.
    Luirink J. and Dobberstein B. (1994) Mammalian and Escherichia coli signal recognition particles. Molecular Microbiology 11: 9–13. [PubMed: 8145649]
    113.
    Onafuwa-Nuga A.A., Telesnitsky A. and King S.R. (2006) 7SL RNA, but not the 54-kd signal recognition particle protein, is an abundant component of both infectious HIV-1 and minimal virus-like particles. RNA 12: 542–546. [PMC free article: PMC1421090] [PubMed: 16489186]
    114.
    Tian C., Wang T., Zhang W. and Yu X.-F. (2007) Virion packaging determinants and reverse transcription of SRP RNA in HIV-1 particles. Nucleic Acids Research 35: 7288–7302. [PMC free article: PMC2175372] [PubMed: 17959647]
    115.
    Wang T. et al. (2007) 7SL RNA mediates virion packaging of the antiviral cytidine deaminase APOBEC3G. Journal of Virology 81: 13112–13124. [PMC free article: PMC2169093] [PubMed: 17881443]
    116.
    Wang T., Tian C., Zhang W., Sarkis P.T.N. and Yu X.-F. (2008) Interaction with 7SL RNA but not with HIV-1 genomic RNA or P Bodies Is required for APOBEC3F virion packaging. Journal of Molecular Biology 375: 1098–1112. [PubMed: 18067920]
    117.
    Itano M.S., Arnion H., Wolin S.L. and Simon S.M. (2018) Recruitment of 7SL RNA to assembling HIV-1 virus-like particles. Traffic 19: 36–43. [PMC free article: PMC6781622] [PubMed: 29044909]
    118.
    Abdelmohsen K. et al. (2014) 7SL RNA represses p53 translation by competing with HuR. Nucleic Acids Research 42: 10099–10111. [PMC free article: PMC4150789] [PubMed: 25123665]
    119.
    Weiner A.M. (1980) An abundant cytoplasmic 7S RNA is complementary to the dominant interspersed middle repetitive DNA-sequence family in the human genome. Cell 22: 209–218. [PubMed: 6159101]
    120.
    Ullu E. and Tschudi C. (1984) Alu sequences are processed 7SL RNA genes. Nature 312: 171–172. [PubMed: 6209580]
    121.
    Quentin Y. (1992) Origin of the Alu family: A family of Alu-like monomers gave birth to the left and the right arms of the Alu elements. Nucleic Acids Research 20: 3397–3401. [PMC free article: PMC312495] [PubMed: 1378589]
    122.
    Wassarman D.A. and Steitz J.A. (1991) Structural analyses of the 7SK ribonucleoprotein (RNP), the most abundant human small RNP of unknown function. Molecular Cell Biology 11: 3432–3445. [PMC free article: PMC361072] [PubMed: 1646389]
    123.
    Ringuette M., Liu W.C., Jay E., Yu K.K. and Krause M.O. (1980) Stimulation of transcription of chromatin by specific small nuclear RNAs. Gene 8: 211–224. [PubMed: 6244212]
    124.
    Sohn U., Szyszko J., Coombs D. and Krause M. (1983) 7S-K nuclear RNA from simian virus 40-transformed cells has sequence homology to the viral early promoter. Proceedings of the National Academy of Sciences USA 80: 7090–7094. [PMC free article: PMC389998] [PubMed: 6196783]
    125.
    Blencowe B.J. (2002) Transcription: Surprising role for an elusive small nuclear RNA. Current Biology 12: R147–9. [PubMed: 11864590]
    126.
    Yang Z., Zhu Q., Luo K. and Zhou Q. (2001) The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414: 317–322. [PubMed: 11713532]
    127.
    Nguyen V.T., Kiss T., Michels A.A. and Bensaude O. (2001) 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414: 322–325. [PubMed: 11713533]
    128.
    Kohoutek J. (2009) P-TEFb- the final frontier. Cell Division 4: 19. [PMC free article: PMC2748068] [PubMed: 19723344]
    129.
    Lenasi T. and Barboric M. (2010) P-TEFb stimulates transcription elongation and pre-mRNA splicing through multilateral mechanisms. RNA Biology 7: 145–150. [PubMed: 20305375]
    130.
    Peterlin B.M., Brogie J.E. and Price D.H. (2012) 7SK snRNA: A noncoding RNA that plays a major role in regulating eukaryotic transcription. Wiley Interdisciplinary Reviews RNA 3: 92–103. [PMC free article: PMC3223291] [PubMed: 21853533]
    131.
    Castelo-Branco G. et al. (2013) The non-coding snRNA 7SK controls transcriptional termination, poising, and bidirectionality in embryonic stem cells. Genome Biology 14: R98. [PMC free article: PMC4053805] [PubMed: 24044525]
    132.
    Quaresma A.J.C., Bugai A. and Barboric M. (2016) Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb. Nucleic Acids Research 44: 7527–7539. [PMC free article: PMC5027500] [PubMed: 27369380]
    133.
    Flynn R.A. et al. (2016) 7SK-BAF axis controls pervasive transcription at enhancers. Nature Structural & Molecular Biology 23: 231–238. [PMC free article: PMC4982704] [PubMed: 26878240]
    134.
    Egloff S., Studniarek C. and Kiss T. (2018) 7SK small nuclear RNA, a multifunctional transcriptional regulatory RNA with gene-specific features. Transcription 9: 95–101. [PMC free article: PMC5834218] [PubMed: 28820318]
    135.
    Gruber A.R. et al. (2008) Invertebrate 7SK snRNAs. Journal of Molecular Evolution 66: 107–115. [PMC free article: PMC2755741] [PubMed: 18193315]
    136.
    Yazbeck A.M., Tout K.R. and Stadler P.F. (2018) Detailed secondary structure models of invertebrate 7SK RNAs. RNA Biology 15: 158–164. [PMC free article: PMC5798955] [PubMed: 29219696]
    137.
    Miller J., McLachlan A.D. and Klug A. (1985) Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO Journal 4: 1609–1614. [PMC free article: PMC554390] [PubMed: 4040853]
    138.
    Klug A. (2010) The discovery of Zinc Fingers and their applications in gene regulation and genome manipulation. Annual Review of Biochemistry 79: 213–231. [PubMed: 20192761]
    139.
    Hu S., Wang X. and Shan G. (2016) Insertion of an Alu element in a lncRNA leads to primate-specific modulation of alternative splicing. Nature Structural & Molecular Biology 23: 1011–1019. [PubMed: 27694840]
    140.
    Pelham H.R. and Brown D.D. (1980) A specific transcription factor that can bind either the 5S RNA gene or 5S RNA. Proceedings of the National Academy of Sciences USA 77: 4170–4174. [PMC free article: PMC349792] [PubMed: 7001457]
    141.
    Honda B.M. and Roeder R.G. (1980) Association of a 5S gene transcription factor with 5S RNA and altered levels of the factor during cell differentiation. Cell 22: 119–126. [PubMed: 6159099]
    142.
    Hendrick J.P., Wolin S.L., Rinke J., Lerner M.R. and Steitz J.A. (1981) Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: Further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. Molecular Cell Biology 1: 1138–1149. [PMC free article: PMC369740] [PubMed: 6180298]
    143.
    Maraia R.J., Sasaki-Tozawa N., Driscoll C.T., Green E.D. and Darlington G.J. (1994) The human Y4 small cytoplasmic RNA gene is controlled by upstream elements and resides on chromosome 7 with all other hY scRNA genes. Nucleic Acids Research 22: 3045–3052. [PMC free article: PMC310274] [PubMed: 7520568]
    144.
    Stein A.J., Fuchs G., Fu C., Wolin S.L. and Reinisch K.M. (2005) Structural insights into RNA quality control: The Ro autoantigen binds misfolded RNAS via its central cavity. Cell 121: 529–539. [PMC free article: PMC1769319] [PubMed: 15907467]
    145.
    Perreault J., Perreault J.P. and Boire G. (2007) Ro-associated Y RNAs in metazoans: Evolution and diversification. Molecular Biology and Evolution 24: 1678–1689. [PubMed: 17470436]
    146.
    Krude T. (2010) Non-coding RNAs: New players in the field of eukaryotic DNA replication, in H.P. Nasheuer (ed.) Genome Stability and Human Diseases. Subcellular Biochemistry,vol. 50, pp. 105–118 (Springer, New York). [PubMed: 20012579]
    147.
    Chen X. et al. (2003) The Ro autoantigen binds misfolded U2 small nuclear RNAs and assists mammalian cell survival after UV Irradiation. Current Biology 13: 2206–2211. [PubMed: 14680639]
    148.
    Fuchs G., Stein A.J., Fu C., Reinisch K.M. and Wolin S.L. (2006) Structural and biochemical basis for misfolded RNA recognition by the Ro autoantigen. Nature Structural & Molecular Biology 13: 1002–1009. [PubMed: 17041599]
    149.
    Sim S. et al. (2009) The subcellular distribution of an RNA quality control protein, the Ro autoantigen, is regulated by noncoding Y RNA binding. Molecular Biology of the Cell 20: 1555–1564. [PMC free article: PMC2649258] [PubMed: 19116308]
    150.
    Chen X. et al. (2007) An ortholog of the Ro autoantigen functions in 23S rRNA maturation in D. radiodurans. Genes & Development 21: 1328–1339. [PMC free article: PMC1877746] [PubMed: 17510283]
    151.
    Wurtmann E.J. and Wolin S.L. (2010) A role for a bacterial ortholog of the Ro autoantigen in starvation-induced rRNA degradation. Proceedings of the National Academy of Sciences USA 107: 4022–4027. [PMC free article: PMC2840137] [PubMed: 20160119]
    152.
    Chen X. et al. (2013) An RNA degradation machine sculpted by Ro autoantigen and noncoding RNA. Cell 153: 166–177. [PMC free article: PMC3646564] [PubMed: 23540697]
    153.
    Sim S., Wolin S.L., Storz G. and Papenfort K. (2018) Bacterial Y RNAs: Gates, tethers, and tRNA mimics. Microbiology Spectrum 6. doi: 10.1128/microbiolspec.RWR-0023-2018. [PMC free article: PMC6047535] [PubMed: 30006996] [CrossRef]
    154.
    Kedersha N.L. and Rome L.H. (1986) Isolation and characterization of a novel ribonucleoprotein particle: Large structures contain a single species of small RNA. Journal of Cell Biology 103: 699–709. [PMC free article: PMC2114306] [PubMed: 2943744]
    155.
    Kedersha N.L., Miquel M.C., Bittner D. and Rome L.H. (1990) Vaults. II. Ribonucleoprotein structures are highly conserved among higher and lower eukaryotes. Journal of Cell Biology 110: 895–901. [PMC free article: PMC2116106] [PubMed: 1691193]
    156.
    van Zon A., Mossink M.H., Scheper R.J., Sonneveld P. and Wiemer E.A. (2003) The vault complex. Cellular and Molecular Life Sciences 60: 1828–1837. [PubMed: 14523546]
    157.
    Horos R. et al. (2019) The small non-coding Vault RNA1-1 acts as a riboregulator of autophagy. Cell 176: 1054–1067. [PubMed: 30773316]
    158.
    Mizushima N. (2007) Autophagy: Process and function. Genes & Development 21: 2861–2873. [PubMed: 18006683]
    159.
    Amort M. et al. (2015) Expression of the vault RNA protects cells from undergoing apoptosis. Nature Communications 6: 7030. [PMC free article: PMC4430821] [PubMed: 25952297]
    160.
    Bracher L. et al. (2020) Human vtRNA1-1 levels modulate signaling pathways and regulate apoptosis in human cancer cells. Biomolecules 10: 614. [PMC free article: PMC7226377] [PubMed: 32316166]
    161.
    Wakatsuki S. et al. (2021) Small noncoding vault RNA modulates synapse formation by amplifying MAPK signaling. Journal of Cell Biology 220: e201911078. [PMC free article: PMC7809882] [PubMed: 33439240]
    162.
    Nallagatla S.R., Toroney R. and Bevilacqua P.C. (2011) Regulation of innate immunity through RNA structure and the protein kinase PKR. Current Opinion in Structural Biology 21: 119–127. [PMC free article: PMC3075410] [PubMed: 21145228]
    163.
    Reich P.R., Forget B.G. and Weissman S.M. (1966) RNA of low molecular weight in KB cells infected with adenovirus type 2. Journal of Molecular Biology 17: 428–439. [PubMed: 5963076]
    164.
    Ohe K. and Weissman S.M. (1971) The nucleotide sequence of a low molecular weight ribonucleic acid from cells infected with adenovirus 2. Journal of Biological Chemistry 246: 6991–7009. [PubMed: 4331202]
    165.
    Mathews M.B. (1975) Genes for VA-RNA in adenovirus 2. Cell 6: 223–229. [PubMed: 1182803]
    166.
    Akusjarvi G., Mathews M.B., Andersson P., Vennstrom B. and Pettersson U. (1980) Structure of genes for virus-associated RNAI and RNAII of adenovirus type 2. Proceedings of the National Academy of Sciences USA 77: 2424–2428. [PMC free article: PMC349411] [PubMed: 6930642]
    167.
    Thimmappaya B., Weinberger C., Schneider R.J. and Shenk T. (1982) Adenovirus VAI RNA is required for efficient translation of viral mRNAs at late times after infection. Cell 31: 543–551. [PubMed: 6297772]
    168.
    Mathews M.B. and Shenk T. (1991) Adenovirus virus-associated RNA and translation control. Journal of Virology 65: 5657–5662. [PMC free article: PMC250225] [PubMed: 1920611]
    169.
    Hood I.V. et al. (2019) Crystal structure of an adenovirus virus-associated RNA. Nature Communications 10: 2871. [PMC free article: PMC6599070] [PubMed: 31253805]
    170.
    Krayev A.S. et al. (1982) Ubiquitous transposon-like repeats B1 and B2 of the mouse genome: B2 sequencing. Nucleic Acids Research 10: 7461–7475. [PMC free article: PMC327023] [PubMed: 6296779]
    171.
    Kramerov D.A., Grigoryan A.A., Ryskov A.P. and Georgiev G.P. (1979) Long double-stranded sequences (dsRNA-B) of nuclear pre-mRNA consist of a few highly abundant classes of sequences: Evidence from DNA cloning experiments. Nucleic Acids Research 6: 697–713. [PMC free article: PMC327722] [PubMed: 370792]
    172.
    Fornace Jr. A.J., and Mitchell J.B. (1986) Induction of B2 RNA polymerase III transcription by heat shock: Enrichment for heat shock induced sequences in rodent cells by hybridization subtraction. Nucleic Acids Research 14: 5793–5811. [PMC free article: PMC311592] [PubMed: 2426659]
    173.
    Sutcliffe J.G., Milner R.J., Gottesfeld J.M. and Lerner R.A. (1984) Identifier sequences are transcribed specifically in brain. Nature 308: 237–241. [PubMed: 6199680]
    174.
    DeChiara T.M. and Brosius J. (1987) Neural BC1 RNA: cDNA clones reveal nonrepetitive sequence content. Proceedings of the National Academy of Sciences USA 84: 2624–2628. [PMC free article: PMC304710] [PubMed: 2437583]
    175.
    Tiedge H., Fremeau Jr. R.T., Weinstock P.H., Arancio O. and Brosius J. (1991) Dendritic location of neural BC1 RNA. Proceedings of the National Academy of Sciences USA 88: 2093–2097. [PMC free article: PMC51175] [PubMed: 1706516]
    176.
    Tiedge H., Chen W. and Brosius J. (1993) Primary structure, neural-specific expression, and dendritic location of human BC200 RNA. Journal of Neuroscience 13: 2382–2390. [PMC free article: PMC6576500] [PubMed: 7684772]
    177.
    Volff J.N. and Brosius J. (2007) Modern genomes with retro-look: Retrotransposed elements, retroposition and the origin of new genes. Gene and Protein Evolution 3: 175–190. [PubMed: 18753792]
    178.
    Lewejohann L. et al. (2004) Role of a neuronal small non-messenger RNA: Behavioural alterations in BC1 RNA-deleted mice. Behavioural Brain Research 154: 273 –89. [PubMed: 15302134]
    179.
    Brutlag D., Schekman R. and Kornberg A. (1971) A possible role for RNA polymerase in the initiation of M13 DNA synthesis. Proceedings of the National Academy of Sciences USA 68: 2826–2829. [PMC free article: PMC389535] [PubMed: 4941987]
    180.
    Sugino A., Hirose S. and Okazaki R. (1972) RNA-linked nascent DNA fragments in Escherichia coli. Proceedings of the National Academy of Sciences USA 69: 1863–1867. [PMC free article: PMC426820] [PubMed: 4558661]
    181.
    Zakian V.A. (2012) Telomeres: The beginnings and ends of eukaryotic chromosomes. Experimental Cell Research 318: 1456–1460. [PMC free article: PMC3372703] [PubMed: 22391099]
    182.
    Yu G.L., Bradley J.D., Attardi L.D. and Blackburn E.H. (1990) In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344: 126–132. [PubMed: 1689810]
    183.
    Greider C.W. and Blackburn E.H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43: 405–413. [PubMed: 3907856]
    184.
    Nakamura T.M. and Cech T.R. (1998) Reversing time: Origin of telomerase. Cell 92: 587–590. [PubMed: 9506510]
    185.
    Curcio M.J. and Belfort M. (2007) The beginning of the end: Links between ancient retroelements and modern telomerases. Proceedings of the National Academy of Sciences USA 104: 9107–9108. [PMC free article: PMC1890453] [PubMed: 17517612]
    186.
    Belfort M., Curcio M.J. and Lue N.F. (2011) Telomerase and retrotransposons: Reverse transcriptases that shaped genomes. Proceedings of the National Academy of Sciences USA 108: 20304–20310. [PMC free article: PMC3251155] [PubMed: 22187457]
    187.
    McEachern M.J., Krauskopf A. and Blackburn E.H. (2000) Telomeres and their control. Annual Review of Genetics 34: 331–358. [PubMed: 11092831]
    188.
    Qi X. et al. (2012) RNA/DNA hybrid binding affinity determines telomerase template-translocation efficiency. EMBO Journal 31: 150–161. [PMC free article: PMC3252576] [PubMed: 21989387]
    189.
    Logeswaran D., Li Y., Podlevsky J.D. and Chen J.J.L. (2021) Monophyletic origin and divergent evolution of animal telomerase RNA. Molecular Biology and Evolution 38: 215–228. [PMC free article: PMC8480181] [PubMed: 32770221]
    190.
    Washietl S., Hofacker I.L. and Stadler P.F. (2005) Fast and reliable prediction of noncoding RNAs. Proceedings of the National Academy of Sciences USA 102: 2454–2459. [PMC free article: PMC548974] [PubMed: 15665081]
    191.
    Miao Z. et al. (2015) RNA-Puzzles Round II: Assessment of RNA structure prediction programs applied to three large RNA structures. RNA 21: 1066–1084. [PMC free article: PMC4436661] [PubMed: 25883046]
    192.
    Backofen R. et al. (2017) RNA-bioinformatics: Tools, services and databases for the analysis of RNA-based regulation. Journal of Biotechnology 261: 76–84. [PubMed: 28554830]
    193.
    Smith M.A., Seemann S.E., Quek X.C. and Mattick J.S. (2017) DotAligner: Identification and clustering of RNA structure motifs. Genome Biology 18: 244. [PMC free article: PMC5747123] [PubMed: 29284541]
    194.
    Griffiths-Jones S. et al. (2005) Rfam: Annotating non-coding RNAs in complete genomes. Nucleic Acids Research 33: D121–4. [PMC free article: PMC540035] [PubMed: 15608160]
    195.
    Kalvari I. et al. (2018) Rfam 13.0: Shifting to a genome-centric resource for non-coding RNA families. Nucleic Acids Research 46: D335–42. [PMC free article: PMC5753348] [PubMed: 29112718]
    196.
    The RNAcentral Consortium (2018) RNAcentral: A hub of information for non-coding RNA sequences. Nucleic Acids Research 47: D221–9. [PMC free article: PMC6324050] [PubMed: 30395267]
    197.
    Crick F.H.C. (1966) Genetic code - yesterday today and tomorrow. Cold Spring Harbor Symposia on Quantitative Biology 31: 3–9. [PubMed: 5237190]
    198.
    Falk R. and Lazcano A. (2012) The forgotten dispute: A.I. Oparin and H.J. Muller on the origin of life. Hist Philos Life Sci 34: 373–390. [PubMed: 23316567]
    199.
    Lazcano A. (2012) The biochemical roots of the RNA world: From zymonucleic acid to ribozymes. History and Philosophy of the Life Sciences 34: 407–423. [PubMed: 23316569]
    200.
    Rich A. (2004) The excitement of discovery. Annual Review of Biochemistry 73: 1–37. [PubMed: 15189135]
    201.
    Orgel L.E. (1968) Evolution of the genetic apparatus. Journal of Molecular Biology 38: 381–393. [PubMed: 5718557]
    202.
    Woese C.R. (1970) The problem of evolving a genetic code. Bioscience 20: 471–485.
    203.
    Orgel L.E. (2004) Prebiotic chemistry and the origin of the RNA world. Critical Reviews in Biochemistry and Molecular Biology 39: 99–123. [PubMed: 15217990]
    204.
    Kruger K. et al. (1982) Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31: 147–157. [PubMed: 6297745]
    205.
    Michel F. and Dujon B. (1983) Conservation of RNA secondary structures in two intron families including mitochondrial-, chloroplast- and nuclear-encoded members. EMBO Journal 2: 33–38. [PMC free article: PMC555082] [PubMed: 11894905]
    206.
    Michel F. and Ferat J.-L. (1995) Structure and activities of group II introns. Annual Review of Biochemistry 64: 435–461. [PubMed: 7574489]
    207.
    Lambowitz A.M. and Zimmerly S. (2004) Mobile group II introns. Annual Review of Genetics 38: 1–35. [PubMed: 15568970]
    208.
    Bonen L. and Vogel J. (2001) The ins and outs of group II introns. Trends in Genetics 17: 322–331. [PubMed: 11377794]
    209.
    Sharp P.A. (1985) On the origin of RNA splicing and introns. Cell 42: 397–400. [PubMed: 2411416]
    210.
    Cavalier-Smith T. (1991) Intron phylogeny: A new hypothesis. Trends in Genetics 7: 145–148. [PubMed: 2068786]
    211.
    Fica S.M., Mefford M.A., Piccirilli J.A. and Staley J.P. (2014) Evidence for a group II intron–like catalytic triplex in the spliceosome. Nature Structural & Molecular Biology 21: 464–471. [PMC free article: PMC4257784] [PubMed: 24747940]
    212.
    Galej W.P. et al. (2016) Cryo-EM structure of the spliceosome immediately after branching. Nature 537: 197–201. [PMC free article: PMC5156311] [PubMed: 27459055]
    213.
    Smathers C.M. and Robart A.R. (2019) The mechanism of splicing as told by group II introns: Ancestors of the spliceosome. Biochimica et Biophysica Acta 1862: 194390. [PubMed: 31202783]
    214.
    Ferat J.L. and Michel F. (1993) Group II self-splicing introns in bacteria. Nature 364: 358–361. [PubMed: 7687328]
    215.
    Irimia M. and Roy S.W. (2014) Origin of spliceosomal introns and alternative splicing. Cold Spring Harbor Perspectives in Biology 6: a016071. [PMC free article: PMC4031966] [PubMed: 24890509]
    216.
    Guerrier-Takada C., Gardiner K., Marsh T., Pace N. and Altman S. (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35: 849–857. [PubMed: 6197186]
    217.
    Walker S.C. and Engelke D.R. (2006) Ribonuclease P: The evolution of an ancient RNA enzyme. Critical Reviews in Biochemistry and Molecular Biology 41: 77–102. [PMC free article: PMC2803672] [PubMed: 16595295]
    218.
    Reddy R. et al. (1981) Characterization and subcellular localization of 7–8S RNAs of Novikoff hepatoma. Journal of Biological Chemistry 256: 8452–8457. [PubMed: 6167578]
    219.
    Lan P. et al. (2020) Structural insight into precursor ribosomal RNA processing by ribonuclease MRP. Science 369: 656–663. [PubMed: 32586950]
    220.
    Chang D.D. and Clayton D.A. (1989) Mouse RNAase MRP RNA is encoded by a nuclear gene and contains a decamer sequence complementary to a conserved region of mitochondrial RNA substrate. Cell 56: 131–139. [PubMed: 2910496]
    221.
    Martin A.N. and Li Y. (2007) RNase MRP RNA and human genetic diseases. Cell Research 17: 219–226. [PubMed: 17189938]
    222.
    Takagi Y., Warashina M., Stec W.J., Yoshinari K. and Taira K. (2001) Recent advances in the elucidation of the mechanisms of action of ribozymes. Nucleic Acids Research 29: 1815–1834. [PMC free article: PMC37246] [PubMed: 11328865]
    223.
    Gilbert W. (1986) The RNA World. Nature 319: 618.
    224.
    Tjhung K.F., Shokhirev M.N., Horning D.P. and Joyce G.F. (2020) An RNA polymerase ribozyme that synthesizes its own ancestor. Proceedings of the National Academy of Sciences USA 117: 2906–2913. [PMC free article: PMC7022166] [PubMed: 31988127]
    225.
    Becker S. et al. (2019) Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides. Science 366: 76–82. [PubMed: 31604305]
    226.
    Lazcano A. (2015) The RNA World and the origin of life: A short history of a tidy evolutionary narrative. BIO Web of Conferences 4: 00013.
    227.
    Fedor M.J. and Williamson J.R. (2005) The catalytic diversity of RNAs. Nature Reviews Molecular Cell Biology 6: 399–412. [PubMed: 15956979]
    228.
    Salehi-Ashtiani K., Lupták A., Litovchick A. and Szostak J.W. (2006) A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science 313: 1788–1792. [PubMed: 16990549]
    229.
    Webb C.-H.T., Riccitelli N.J., Ruminski D.J. and Lupták A. (2009) Widespread occurrence of self-cleaving ribozymes. Science 326: 953. [PMC free article: PMC3159031] [PubMed: 19965505]
    230.
    de la Peña M. and García-Robles I. (2010) Intronic hammerhead ribozymes are ultraconserved in the human genome. EMBO Reports 11: 711–716. [PMC free article: PMC2933863] [PubMed: 20651741]
    231.
    De la Peña M., García-Robles I. and Cervera A. (2017) The hammerhead ribozyme: A long history for a short RNA. Molecules 22: 78. [PMC free article: PMC6155905] [PubMed: 28054987]
    232.
    Perreault J. et al. (2011) Identification of hammerhead ribozymes in all domains of life reveals novel structural variations. PLOS Computational Biology 7: e1002031. [PMC free article: PMC3088659] [PubMed: 21573207]
    233.
    Hernandez A.J. et al. (2020) B2 and ALU retrotransposons are self-cleaving ribozymes whose activity is enhanced by EZH2. Proceedings of the National Academy of Sciences USA 117: 415–425. [PMC free article: PMC6955291] [PubMed: 31871160]
    234.
    Chen Y. et al. (2021) Hovlinc is a recently evolved class of ribozyme found in human lncRNA. Nature Chemical Biology 17: 601–607. [PubMed: 33753927]
    235.
    Scheitl C.P.M., Ghaem Maghami M., Lenz A.-K. and Höbartner C. (2020) Site-specific RNA methylation by a methyltransferase ribozyme. Nature 587: 663–667. [PMC free article: PMC7116789] [PubMed: 33116304]
    236.
    Wolk S.K. et al. (2020) Modified nucleotides may have enhanced early RNA catalysis. Proceedings of the National Academy of Sciences USA 117: 8236–8242. [PMC free article: PMC7165471] [PubMed: 32229566]
    237.
    Noller H.F., Hoffarth V. and Zimniak L. (1992) Unusual resistance of peptidyl transferase to protein extraction procedures. Science 256: 1416–1419. [PubMed: 1604315]
    238.
    Steitz T.A. and Moore P.B. (2003) RNA, the first macromolecular catalyst: The ribosome is a ribozyme. Trends in Biochemical Sciences 28: 411–418. [PubMed: 12932729]
    239.
    Lambowitz A.M. and Belfort M. (1993) Introns as mobile genetic elements. Annual Review of Biochemistry 62: 587–622. [PubMed: 8352597]
    240.
    Wallis M.G. and Schroeder R. (1997) The binding of antibiotics to RNA. Progress in Biophysics and Molecular Biology 67: 141–154. [PubMed: 9446933]
    241.
    Gallego J. and Varani G. (2001) Targeting RNA with small-molecule drugs:  therapeutic promise and chemical challenges. Accounts of Chemical Research 34: 836–843. [PubMed: 11601968]
    242.
    Schneider-Poetsch T., Chhipi-Shrestha J.K. and Yoshida M. (2021) Splicing modulators: On the way from nature to clinic. The Journal of Antibiotics 74: 603–616. [PMC free article: PMC8472923] [PubMed: 34345042]
    243.
    Endo Y., Mitsui K., Motizuki M. and Tsurugi K. (1987) The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28S ribosomal RNA caused by the toxins. Journal of Biological Chemistry 262: 5908–5912. [PubMed: 3571242]
    244.
    Westhof E. and Fritsch V. (2000) RNA folding: Beyond Watson–Crick pairs. Structure 8: R55–65. [PubMed: 10745012]
    245.
    Westhof E., Masquida B. and Jossinet F. (2011) Predicting and modeling RNA architecture. Cold Spring Harbor Perspectives in Biology 3: a003632. [PMC free article: PMC3039537] [PubMed: 20504963]
    246.
    Westhof E. and Fritsch V. (2011) The endless subtleties of RNA-protein complexes. Structure 19: 902–903. [PubMed: 21742256]
    247.
    Crossley M.P., Bocek M. and Cimprich K.A. (2019) R-loops as cellular regulators and genomic threats. Molecular Cell 73: 398–411. [PMC free article: PMC6402819] [PubMed: 30735654]
    248.
    Cetin N.S. et al. (2019) Isolation and genome-wide characterization of cellular DNA:RNA triplex structures. Nucleic Acids Research 47: 2306–2321. [PMC free article: PMC6411930] [PubMed: 30605520]
    249.
    Tuerk C. and Gold L. (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249: 505–510. [PubMed: 2200121]
    250.
    Ellington A.D. and Szostak J.W. (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346: 818–822. [PubMed: 1697402]
    251.
    Muotri A.R., da Veiga Pereira L., dos Reis Vasques L. and Menck C.F.M. (1999) Ribozymes and the anti-gene therapy: How a catalytic RNA can be used to inhibit gene function. Gene 237: 303–310. [PubMed: 10521654]
    252.
    Gawande B.N. et al. (2017) Selection of DNA aptamers with two modified bases. Proceedings of the National Academy of Sciences USA 114: 2898–2903. [PMC free article: PMC5358403] [PubMed: 28265062]
    253.
    Gold L., Singer B., He Y.Y. and Brody E. (1997) SELEX and the evolution of genomes. Current Opinion in Genetics and Development 7: 848–851. [PubMed: 9468797]
    254.
    Diener T.O. (1971) Potato spindle tuber “virus”. IV. A replicating, low molecular weight RNA. Virology 45: 411–428. [PubMed: 5095900]
    255.
    Sanger H.L., Klotz G., Riesner D., Gross H.J. and Kleinschmidt A.K. (1976) Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proceedings of the National Academy of Sciences USA 73: 3852–3856. [PMC free article: PMC431239] [PubMed: 1069269]
    256.
    Diener T.O. (2016) Viroids: “living fossils” of primordial RNAs? Biology Direct 11: 15. [PMC free article: PMC4807594] [PubMed: 27016066]
    257.
    Mills D.R., Peterson R.L. and Spiegelman S. (1967) An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule. Proceedings of the National Academy of Sciences USA 58: 217–224. [PMC free article: PMC335620] [PubMed: 5231602]
    258.
    Kaper J.M. and Waterworth H.E. (1977) Cucumber mosaic virus associated RNA 5: Causal agent for tomato necrosis. Science 196: 429–431. [PubMed: 17776951]
    259.
    Hillman B.I., Carrington J.C. and Morris T.J. (1987) A defective interfering RNA that contains a mosaic of a plant virus genome. Cell 51: 427–433. [PubMed: 3664641]
    260.
    Simon A.E., Roossinck M.J. and Havelda Z. (2004) Plant virus satellite and defective interfering RNAs: New paradigms for a new century. Annual Review of Phytopathology 42: 415–437. [PubMed: 15283672]
    261.
    Joyce G.F. (1991) The rise and fall of the RNA world. New Biologist 3: 399–407. [PubMed: 1712228]
    262.
    Penman S. (1991) If genes just make proteins and our proteins are the same, then why are we so different? Journal of Cellular Biochemistry 47: 95–98. [PubMed: 1757482]

    Chapter 9

    1.
    Marx J.L. (1984) New ways to “mutate” genes. Science 225: 819. [PubMed: 6474154]
    2.
    Zamecnik P.C. and Stephenson M.L. (1978) Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proceedings of the National Academy of Sciences USA 75: 280–284. [PMC free article: PMC411230] [PubMed: 75545]
    3.
    Zamecnik P.C., Goodchild J., Taguchi Y. and Sarin P.S. (1986) Inhibition of replication and expression of human T-cell lymphotropic virus type III in cultured cells by exogenous synthetic oligonucleotides complementary to viral RNA. Proceedings of the National Academy of Sciences USA 83: 4143–4146. [PMC free article: PMC323687] [PubMed: 3012555]
    4.
    Hindley J. (1967) Fractionation of 32P-labelled ribonucleic acids on polyacrylamide gels and their characterization by fingerprinting. Journal of Molecular Biology 30: 125–136. [PubMed: 4865141]
    5.
    Wassarman K.M. and Storz G. (2000) 6S RNA regulates E. coli RNA polymerase activity. Cell 101: 613–623. [PubMed: 10892648]
    6.
    Trotochaud A.E. and Wassarman K.M. (2005) A highly conserved 6S RNA structure is required for regulation of transcription. Nature Structural & Molecular Biology 12: 313–319. [PubMed: 15793584]
    7.
    Steuten B. et al. (2014) Regulation of transcription by 6S RNAs. RNA Biology 11: 508–521. [PMC free article: PMC4152359] [PubMed: 24786589]
    8.
    Schleich T. and Goldstein J. (1964) Gel filtration properties of ccd-prepared E. coli B sRNA. Proceedings of the National Academy of Sciences USA 52: 744–749. [PMC free article: PMC300340] [PubMed: 14212552]
    9.
    Goldstein J. and Harewood K. (1969) Another species of ribonucleic acid in Escherichia coli. Journal of Molecular Biology 39: 383–387. [PubMed: 4903177]
    10.
    Spiegelman W.G. et al. (1972) Bidirectional transcription and the regulation of phage lambda repressor synthesis. Proceedings of the National Academy of Sciences USA 69: 3156–3160. [PMC free article: PMC389725] [PubMed: 4508309]
    11.
    Shaw D.C. et al. (1978) Gene K, a new overlapping gene in bacteriophage G4. Nature 272: 510–515. [PubMed: 692656]
    12.
    Sanger F. et al. (1977) Nucleotide sequence of bacteriophage phi X174 DNA. Nature 265: 687–695. [PubMed: 870828]
    13.
    Fiers W. et al. (1978) Complete nucleotide sequence of SV40 DNA. Nature 273: 113–120. [PubMed: 205802]
    14.
    Contreras R., Rogiers R., Van de Voorde A. and Fiers W. (1977) Overlapping of the VP2-VP3 gene and the VP1 gene in the SV40 genome. Cell 12: 529–538. [PubMed: 199354]
    15.
    Oh B.-K. and Apirion D. (1991) 10Sa RNA, a small stable RNA of Escherichia coli, is functional. Molecular and General Genetics 229: 52–56. [PubMed: 1716727]
    16.
    Komine Y., Kitabatake M., Yokogawa T., Nishikawa K. and Inokuchi H. (1994) A tRNA-like structure is present in 10Sa RNA, a small stable RNA from Escherichia coli. Proceedings of the National Academy of Sciences USA 91: 9223–9227. [PMC free article: PMC44784] [PubMed: 7524073]
    17.
    Muto A. et al. (1996) Structure and function of 10Sa RNA: Trans-translation system. Biochimie 78: 985–991. [PubMed: 9150876]
    18.
    Moriano-Gutierrez S. et al. (2020) The noncoding small RNA SsrA is released by Vibrio fischeri and modulates critical host responses. PLOS Biology 18: e3000934. [PMC free article: PMC7665748] [PubMed: 33141816]
    19.
    Walker S.C. and Engelke D.R. (2006) Ribonuclease P: The evolution of an ancient RNA enzyme. Critical Reviews in Biochemistry and Molecular Biology 41: 77–102. [PMC free article: PMC2803672] [PubMed: 16595295]
    20.
    Ray B.K. and Apirion D. (1979) Characterization of 10S RNA: A new stable RNA molecule from Escherichia coli. Molecular and General Genetics 174: 25–32. [PubMed: 384159]
    21.
    Jain S.K., Gurevitz M. and Apirion D. (1982) A small RNA that complements mutants in the RNA processing enzyme ribonuclease P. Journal of Molecular Biology 162: 515–533. [PubMed: 6187924]
    22.
    Gralla J., Steitz J.A. and Crothers D.M. (1974) Direct physical evidence for secondary structure in an isolated fragment of R17 bacteriophage mRNA. Nature 248: 204–208. [PubMed: 4819414]
    23.
    Lemaire G., Gold L. and Yarus M. (1978) Autogenous translational repression of bacteriophage T4 gene 32 expression in vitro. Journal of Molecular Biology 126: 73–90. [PubMed: 739544]
    24.
    Fallon A.M., Jinks C.S., Strycharz G.D. and Nomura M. (1979) Regulation of ribosomal protein synthesis in Escherichia coli by selective mRNA inactivation. Proceedings of the National Academy of Sciences USA 76: 3411–3415. [PMC free article: PMC383835] [PubMed: 158759]
    25.
    Olins P.O. and Nomura M. (1981) Translational regulation by ribosomal protein S8 in Escherichia coli: Structural homology between rRNA binding site and feedback target on mRNA. Nucleic Acids Research 9: 1757–1764. [PMC free article: PMC326795] [PubMed: 6262737]
    26.
    Meyer B.J. (2019) rRNA mimicry in RNA regulation of gene expression, in G. Storz and K. Papenfort (ed.) Regulating with RNA in Bacteria and Archaea (ASM Press, New York).
    27.
    Bester A.J., Kennedy D.S. and Heywood S.M. (1975) Two classes of translational control RNA: Their role in the regulation of protein synthesis. Proceedings of the National Academy of Sciences USA 72: 1523–1527. [PMC free article: PMC432569] [PubMed: 1055423]
    28.
    Heywood S.M., Kennedy D.S. and Bester A.J. (1975) Studies concerning the mechanism by which translational-control RNA regulates protein synthesis in embryonic muscle. European Journal of Biochemistry 58: 587–593. [PubMed: 1237405]
    29.
    McCarthy T.L., Siegel E., Mroczkowski B. and Heywood S.M. (1983) Characterization of translational-control ribonucleic acid isolated from embryonic chick muscle. Biochemistry 22: 935–941. [PubMed: 6188483]
    30.
    Heywood S.M. (1986) tcRNA as a naturally occurring antisense RNA in eukaryotes. Nucleic Acids Research 14: 6771–6772. [PMC free article: PMC311684] [PubMed: 3748824]
    31.
    Tomizawa J. and Itoh T. (1981) Plasmid ColE1 incompatibility determined by interaction of RNA I with primer transcript. Proceedings of the National Academy of Sciences USA 78: 6096–6100. [PMC free article: PMC348984] [PubMed: 6171811]
    32.
    Stougaard P., Molin S. and Nordstrom K. (1981) RNAs involved in copy-number control and incompatibility of plasmid R1. Proceedings of the National Academy of Sciences USA 78: 6008–6012. [PMC free article: PMC348966] [PubMed: 6171808]
    33.
    Rosen J., Ryder T., Ohtsubo H. and Ohtsubo E. (1981) Role of RNA transcripts in replication incompatibility and copy number control in antibiotic resistance plasmid derivatives. Nature 290: 794–797. [PubMed: 6163994]
    34.
    Simons R.W. and Kleckner N. (1983) Translational control of IS10 transposition. Cell 34: 683–691. [PubMed: 6311438]
    35.
    Mizuno T., Chou M.Y. and Inouye M. (1984) A unique mechanism regulating gene expression: Translational inhibition by a complementary RNA transcript (micRNA). Proceedings of the National Academy of Sciences USA 81: 1966–1970. [PMC free article: PMC345417] [PubMed: 6201848]
    36.
    Guo P.X., Erickson S. and Anderson D. (1987) A small viral RNA is required for in vitro packaging of bacteriophage phi 29 DNA. Science 236: 690–694. [PubMed: 3107124]
    37.
    Simons R.W. and Kleckner N. (1988) Biological regulation by antisense RNA in prokaryotes. Annual Review of Genetics 22: 567–600. [PubMed: 2467619]
    38.
    Inouye M. and Delihast N. (1988) Small RNAs in the prokaryotes: A growing list of diverse roles. Cell 53: 5–7. [PubMed: 2450678]
    39.
    Papenfort K. and Vogel J. (2010) Regulatory RNA in bacterial pathogens. Cell Host & Microbe 8: 116–127. [PubMed: 20638647]
    40.
    Novick R.P. et al. (1993) Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO journal 12: 3967–3975. [PMC free article: PMC413679] [PubMed: 7691599]
    41.
    Chevalier C. et al. (2010) Staphylococcus aureus RNAIII binds to two distant regions of coa mRNA to arrest translation and promote mRNA degradation. PLOS Pathogens 6: e1000809. [PMC free article: PMC2837412] [PubMed: 20300607]
    42.
    Wassarman K.M., Zhang A. and Storz G. (1999) Small RNAs in Escherichia coli. Trends in Microbiology 7: 37–45. [PubMed: 10068996]
    43.
    Waters L.S. and Storz G. (2009) Regulatory RNAs in bacteria. Cell 136: 615–628. [PMC free article: PMC3132550] [PubMed: 19239884]
    44.
    Livny J. and Waldor M.K. (2007) Identification of small RNAs in diverse bacterial species. Current Opinion in Microbiology 10: 96–101. [PubMed: 17383222]
    45.
    Sharma C.M. and Vogel J. (2009) Experimental approaches for the discovery and characterization of regulatory small RNA. Current Opinion in Microbiology 12: 536–546. [PubMed: 19758836]
    46.
    Li L. et al. (2012) BSRD: A repository for bacterial small regulatory RNA. Nucleic Acids Research 41: D233–8. [PMC free article: PMC3531160] [PubMed: 23203879]
    47.
    Tree J.J., Granneman S., McAteer S.P., Tollervey D. and Gally D.L. (2014) Identification of bacteriophage-encoded anti-sRNAs in pathogenic Escherichia coli. Molecular Cell 55: 199–213. [PMC free article: PMC4104026] [PubMed: 24910100]
    48.
    Melamed S. et al. (2016) Global mapping of small RNA-target interactions in bacteria. Molecular Cell 63: 884–897. [PMC free article: PMC5145812] [PubMed: 27588604]
    49.
    Waters S.A. et al. (2017) Small RNA interactome of pathogenic E. coli revealed through crosslinking of RNase E. EMBO Journal 36: 374–387. [PMC free article: PMC5286369] [PubMed: 27836995]
    50.
    Hör J. and Vogel J. (2017) Global snapshots of bacterial RNA networks. EMBO Journal 36: 245–247. [PMC free article: PMC5286387] [PubMed: 28031253]
    51.
    Sledjeski D.D., Gupta A. and Gottesman S. (1996) The small RNA, DsrA, is essential for the low temperature expression of RpoS during exponential growth in Escherichia coli. EMBO Journal 15: 3993–4000. [PMC free article: PMC452119] [PubMed: 8670904]
    52.
    Sledjeski D. and Gottesman S. (1995) A small RNA acts as an antisilencer of the H-NS-silenced rcsA gene of Escherichia coli. Proceedings of the National Academy of Sciences USA 92: 2003–2007. [PMC free article: PMC42411] [PubMed: 7534408]
    53.
    Majdalani N., Cunning C., Sledjeski D., Elliott T. and Gottesman S. (1998) DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription. Proceedings of the National Academy of Sciences USA 95: 12462–12467. [PMC free article: PMC22853] [PubMed: 9770508]
    54.
    Altuvia S., WeinsteinFischer D., Zhang A.X., Postow L. and Storz G. (1997) A small, stable RNA induced by oxidative stress: Role as a pleiotropic regulator and antimutator. Cell 90: 43–53. [PubMed: 9230301]
    55.
    Zhang A. et al. (1998) The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF-I) protein. EMBO Journal 17: 6061–6068. [PMC free article: PMC1170932] [PubMed: 9774349]
    56.
    Franze de Fernandez M.T., Eoyang L. and August J.T. (1968) Factor fraction required for the synthesis of bacteriophage Qβ-RNA. Nature 219: 588–590. [PubMed: 4874917]
    57.
    Møller T. et al. (2002) Hfq: A bacterial Sm-like protein that mediates RNA-RNA interaction. Molecular Cell 9: 23–30. [PubMed: 11804583]
    58.
    Gottesman S. (2004) The small RNA regulators of Escherichia coli: Roles and mechanisms. Annual Review of Microbiology 58: 303–328. [PubMed: 15487940]
    59.
    Majdalani N., Vanderpool C.K. and Gottesman S. (2005) Bacterial small RNA regulators. Critical Reviews in Biochemistry and Molecular Biology 40: 93–113. [PubMed: 15814430]
    60.
    Wassarman K.M., Repoila F., Rosenow C., Storz G. and Gottesman S. (2001) Identification of novel small RNAs using comparative genomics and microarrays. Genes & Development 15: 1637–1651. [PMC free article: PMC312727] [PubMed: 11445539]
    61.
    Zhang A., Wassarman K.M., Ortega J., Steven A.C. and Storz G. (2002) The Sm-like Hfq protein increases OxyS RNA interaction with target mRNAs. Molecular Cell 9: 11–22. [PubMed: 11804582]
    62.
    Geissmann T.A. and Touati D. (2004) Hfq, a new chaperoning role: Binding to messenger RNA determines access for small RNA regulator. EMBO Journal 23: 396–405. [PMC free article: PMC1271764] [PubMed: 14739933]
    63.
    Lenz D.H. et al. (2004) The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118: 69–82. [PubMed: 15242645]
    64.
    Chao Y. and Vogel J. (2010) The role of Hfq in bacterial pathogens. Current Opinion in Microbiology 13: 24–33. [PubMed: 20080057]
    65.
    Fuchs M. et al. (2021) An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium. Proceedings of the National Academy of Sciences USA 118: e2103579118. [PMC free article: PMC8237595] [PubMed: 34131082]
    66.
    Lucchetti-Miganeh C., Burrowes E., Baysse C. and Ermel G. (2008) The post-transcriptional regulator CsrA plays a central role in the adaptation of bacterial pathogens to different stages of infection in animal hosts. Microbiology 154: 16–29. [PubMed: 18174122]
    67.
    Sy B.M., Lan R. and Tree J.J. (2020) Early termination of the Shiga toxin transcript generates a regulatory small RNA. Proceedings of the National Academy of Sciences USA 117: 25055–25065. [PMC free article: PMC7547250] [PubMed: 32968018]
    68.
    Zhao E.M. et al. (2021) RNA-responsive elements for eukaryotic translational control. Nature Biotechnology epub ahead of print: https://doi​.org/10.1038​/s41587-021-01068-2. [PubMed: 34711989]
    69.
    Huang F., Yang Z. and Yarus M. (1998) RNA enzymes with two small-molecule substrates. Chemistry & Biology 5: 669–678. [PubMed: 9831528]
    70.
    Winkler W.C., Nahvi A., Roth A., Collins J.A. and Breaker R.R. (2004) Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428: 281–286. [PubMed: 15029187]
    71.
    Winkler W., Nahvi A. and Breaker R.R. (2002) Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419: 952–956. [PubMed: 12410317]
    72.
    Mironov A.S. et al. (2002) Sensing small molecules by nascent RNA: A mechanism to control transcription in bacteria. Cell 111: 747–756. [PubMed: 12464185]
    73.
    Winkler W.C., Nahvi A., Sudarsan N., Barrick J.E. and Breaker R.R. (2003) An mRNA structure that controls gene expression by binding S-adenosylmethionine. Nature Structural Biology 10: 701–707. [PubMed: 12910260]
    74.
    Winkler W.C. (2005) Riboswitches and the role of noncoding RNAs in bacterial metabolic control. Current Opinion in Chemical Biology 9: 594–602. [PubMed: 16226486]
    75.
    Nudler E. and Mironov A.S. (2004) The riboswitch control of bacterial metabolism. Trends in Biochemical Sciences 29: 11–17. [PubMed: 14729327]
    76.
    Chowdhury S., Maris C., Allain F.H. and Narberhaus F. (2006) Molecular basis for temperature sensing by an RNA thermometer. EMBO Journal 25: 2487–2497. [PMC free article: PMC1478195] [PubMed: 16710302]
    77.
    Loh E. et al. (2009) A trans-acting riboswitch controls expression of the virulence regulator PrfA in Listeria monocytogenes. Cell 139: 770–779. [PubMed: 19914169]
    78.
    Stormo G.D. (2003) New tricks for an old dogma: Riboswitches as cis-only regulatory systems. Molecular Cell 11: 1419–1420. [PubMed: 12820954]
    79.
    Winkler W.C. and Breaker R.R. (2005) Regulation of bacterial gene expression by riboswitches. Annual Review of Microbiology 59: 487–517. [PubMed: 16153177]
    80.
    Nudler E. (2006) Flipping riboswitches. Cell 126: 19–22. [PubMed: 16839869]
    81.
    Serganov A. and Patel D.J. (2007) Ribozymes, riboswitches and beyond: Regulation of gene expression without proteins. Nature Reviews Genetics 8: 776–790. [PMC free article: PMC4689321] [PubMed: 17846637]
    82.
    Brewer K.I. et al. (2021) Comprehensive discovery of novel structured noncoding RNAs in 26 bacterial genomes. RNA Biology 18: 2417–2432. [PMC free article: PMC8632094] [PubMed: 33970790]
    83.
    Chauvier A. et al. (2021) Monitoring RNA dynamics in native transcriptional complexes. Proceedings of the National Academy of Sciences USA 118: e2106564118. [PMC free article: PMC8609307] [PubMed: 34740970]
    84.
    Montange R.K. and Batey R.T. (2006) Structure of the S-adenosylmethionine riboswitch regulatory mRNA element. Nature 441: 1172–1175. [PubMed: 16810258]
    85.
    Tang D.-J. et al. (2020) A SAM-I riboswitch with the ability to sense and respond to uncharged initiator tRNA. Nature Communications 11: 2794. [PMC free article: PMC7270179] [PubMed: 32493973]
    86.
    Bocobza S. et al. (2007) Riboswitch-dependent gene regulation and its evolution in the plant kingdom. Genes & Development 21: 2874–2879. [PMC free article: PMC2049190] [PubMed: 18006684]
    87.
    Donovan P.D. et al. (2018) TPP riboswitch-dependent regulation of an ancient thiamin transporter in Candida. PLOS Genetics 14: e1007429. [PMC free article: PMC5997356] [PubMed: 29852014]
    88.
    McRose D. et al. (2014) Alternatives to vitamin B1 uptake revealed with discovery of riboswitches in multiple marine eukaryotic lineages. The ISME Journal 8: 2517–2529. [PMC free article: PMC4260697] [PubMed: 25171333]
    89.
    Cheah M.T., Wachter A., Sudarsan N. and Breaker R.R. (2007) Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature 447: 497–500. [PubMed: 17468745]
    90.
    Pham H.L. et al. (2017) Engineering a riboswitch-based genetic platform for the self-directed evolution of acid-tolerant phenotypes. Nature Communications 8: 411. [PMC free article: PMC5583362] [PubMed: 28871084]
    91.
    Dhamodharan V., Nomura Y., Dwidar M. and Yokobayashi Y. (2018) Optochemical control of gene expression by photocaged guanine and riboswitches. Chemical Communications 54: 6181–6183. [PubMed: 29845982]
    92.
    Kim D.S., Gusti V., Pillai S.G. and Gaur R.K. (2005) An artificial riboswitch for controlling pre-mRNA splicing. RNA 11: 1667–1677. [PMC free article: PMC1370853] [PubMed: 16244133]
    93.
    Vitreschak A.G., Rodionov D.A., Mironov A.A. and Gelfand M.S. (2004) Riboswitches: The oldest mechanism for the regulation of gene expression? Trends in Genetics 20: 44–50. [PubMed: 14698618]
    94.
    Breaker R.R. (2012) Riboswitches and the RNA world. Cold Spring Harbor Perspectives in Biology 4: a003566. [PMC free article: PMC3281570] [PubMed: 21106649]
    95.
    Plesner P., Goodchild J., Kalckar H.M. and Zamecnik P.C. (1987) Oligonucleotides with rapid turnover of the phosphate groups occur endogenously in eukaryotic cells. Proceedings of the National Academy of Sciences USA 84: 1936–1939. [PMC free article: PMC304556] [PubMed: 3470767]
    96.
    Paterson B.M., Roberts B.E. and Kuff E.L. (1977) Structural gene identification and mapping by DNA-mRNA hybrid-arrested cell-free translation. Proceedings of the National Academy of Sciences USA 74: 4370–4374. [PMC free article: PMC431943] [PubMed: 270678]
    97.
    Both G.W., Mattick J.S. and Bellamy A.R. (1983) Serotype-specific glycoprotein of simian 11 rotavirus: Coding assignment and gene sequence. Proceedings of the National Academy of Sciences USA 80: 3091–3095. [PMC free article: PMC393980] [PubMed: 6304692]
    98.
    Pestka S., Daugherty B.L., Jung V., Hotta K. and Pestka R.K. (1984) Anti-mRNA: Specific inhibition of translation of single mRNA molecules. Proceedings of the National Academy of Sciences USA 81: 7525–7528. [PMC free article: PMC392179] [PubMed: 6438637]
    99.
    Rosenberg U.B., Preiss A., Seifert E., Jackle H. and Knipple D.C. (1985) Production of phenocopies by Kruppel antisense RNA injection into Drosophila embryos. Nature 313: 703–706. [PubMed: 2579337]
    100.
    Melton D.A. (1985) Injected anti-sense RNAs specifically block messenger RNA translation in vivo. Proceedings of the National Academy of Sciences USA 82: 144–148. [PMC free article: PMC396988] [PubMed: 3855537]
    101.
    McGarry T.J. and Lindquist S. (1986) Inhibition of heat shock protein synthesis by heat-inducible antisense RNA. Proceedings of the National Academy of Sciences USA 83: 399–403. [PMC free article: PMC322866] [PubMed: 2417242]
    102.
    Kim S.K. and Wold B.J. (1985) Stable reduction of thymidine kinase activity in cells expressing high levels of anti-sense RNA. Cell 42: 129–138. [PubMed: 2410135]
    103.
    Izant J.G. and Weintraub H. (1984) Inhibition of thymidine kinase gene expression by anti-sense RNA: A molecular approach to genetic analysis. Cell 36: 1007–1015. [PubMed: 6323013]
    104.
    Izant J.G. and Weintraub H. (1985) Constitutive and conditional suppression of exogenous and endogenous genes by anti-sense RNA. Science 229: 345–352. [PubMed: 2990048]
    105.
    Crooke S.T. (2011) The Isis manifesto. Bioentrepreneur. https://doi​.org/10.1038/bioe.2011.7.
    106.
    Crooke S.T., Liang X.-H., Baker B.F. and Crooke R.M. (2021) Antisense technology: A review. Journal of Biological Chemistry 296: 100416. [PMC free article: PMC8005817] [PubMed: 33600796]
    107.
    Kurreck J. (2003) Antisense technologies. European Journal of Biochemistry 270: 1628–1644. [PubMed: 12694176]
    108.
    Crooke S.T. (2004) Progress in antisense technology. Annual Review of Medicine 55: 61–95. [PubMed: 14746510]
    109.
    Crooke S.T. (2017) Molecular mechanisms of antisense oligonucleotides. Nucleic Acid Therapeutics 27: 70–77. [PMC free article: PMC5372764] [PubMed: 28080221]
    110.
    Bennett C.F. (2019) Therapeutic antisense oligonucleotides are coming of age. Annual Review of Medicine 70: 307–321. [PubMed: 30691367]
    111.
    Shen W. et al. (2019) Chemical modification of PS-ASO therapeutics reduces cellular protein-binding and improves the therapeutic index. Nature Biotechnology 37: 640–650. [PubMed: 31036929]
    112.
    Travers A. (1984) Regulation by anti-sense RNA. Nature 311: 410. [PubMed: 6207433]
    113.
    Rosen C.A., Sodroski J.G. and Haseltine W.A. (1985) The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell 41: 813–823. [PubMed: 2988790]
    114.
    Kao S.Y., Calman A.F., Luciw P.A. and Peterlin B.M. (1987) Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product. Nature 330: 489–493. [PubMed: 2825027]
    115.
    Feng S. and Holland E.C. (1988) HIV-1 tat trans-activation requires the loop sequence within tar. Nature 334: 165–167. [PubMed: 3386755]
    116.
    Tycowski K.T. et al. (2015) Viral noncoding RNAs: More surprises. Genes & Development 29: 567–584. [PMC free article: PMC4378190] [PubMed: 25792595]
    117.
    Greenaway P.J. and Wilkinson G.W.G. (1987) Nucleotide sequence of the most abundantly transcribed early gene of human cytomegalovirus strain AD169. Virus Research 7: 17–31. [PubMed: 2436392]
    118.
    Reeves M.B., Davies A.A., McSharry B.P., Wilkinson G.W. and Sinclair J.H. (2007) Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science 316: 1345–1348. [PubMed: 17540903]
    119.
    Diatchenko L. et al. (1996) Suppression subtractive hybridization: A method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proceedings of the National Academy of Sciences USA 93: 6025–6030. [PMC free article: PMC39182] [PubMed: 8650213]
    120.
    Henikoff S., Keene M.A., Fechtel K. and Fristrom J.W. (1986) Gene within a gene: Nested Drosophila genes encode unrelated proteins on opposite DNA strands. Cell 44: 33–42. [PubMed: 3079672]
    121.
    Williams T. and Fried M. (1986) A mouse locus at which transcription from both DNA strands produces mRNAs complementary at their 3′ ends. Nature 322: 275–279. [PubMed: 2874494]
    122.
    Spencer C.A., Gietz R.D. and Hodgetts R.B. (1986) Overlapping transcription units in the dopa decarboxylase region of Drosophila. Nature 322: 279–281. [PubMed: 2874495]
    123.
    Spencer C.A., Gietz R.D. and Hodgetts R.B. (1986) Analysis of the transcription unit adjacent to the 3′-end of the dopa decarboxylase gene in Drosophila melanogaster. Developmental Biology 114: 260–264. [PubMed: 3007242]
    124.
    Carninci P. et al. (2005) The transcriptional landscape of the mammalian genome. Science 309: 1559–1563. [PubMed: 16141072]
    125.
    Frith M.C., Pheasant M. and Mattick J.S. (2005) The amazing complexity of the human transcriptome. European Journal of Human Genetics 13: 894–897. [PubMed: 15970949]
    126.
    Mattick J.S. and Makunin I.V. (2006) Non-coding RNA. Human Molecular Genetics 15: R17–29. [PubMed: 16651366]
    127.
    Nepveu A. and Marcu K.B. (1986) Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO Journal 5: 2859–2865. [PMC free article: PMC1167235] [PubMed: 3024965]
    128.
    Kindy M.S., McCormack J.E., Buckler A.J., Levine R.A. and Sonenshein G.E. (1987) Independent regulation of transcription of the two strands of the c-myc gene. Molecular and Cellular Biology 7: 2857–2862. [PMC free article: PMC367903] [PubMed: 3499566]
    129.
    Khochbin S. and Lawrence J.J. (1989) An antisense RNA involved in p53 mRNA maturation in murine erythroleukemia cells induced to differentiate. EMBO Journal 8: 4107–4114. [PMC free article: PMC401592] [PubMed: 2480234]
    130.
    Skeiky Y.A. and Iatrou K. (1990) Silkmoth chorion antisense RNA. Structural characterization, developmental regulation and evolutionary conservation. Journal of Molecular Biology 213: 53–66. [PubMed: 1692592]
    131.
    Thrash-Bingham C.A. and Tartof K.D. (1999) aHIF: A natural antisense transcript overexpressed in human renal cancer and during hypoxia. Journal of the National Cancer Institute 91: 143–151. [PubMed: 9923855]
    132.
    Silverman T.A., Noguchi M. and Safer B. (1992) Role of sequences within the first intron in the regulation of expression of eukaryotic initiation factor 2 alpha. Journal of Biological Chemistry 267: 9738–9742. [PubMed: 1374407]
    133.
    Farrell C.M. and Lukens L.N. (1995) Naturally occurring antisense transcripts are present in chick embryo chondrocytes simultaneously with the down-regulation of the alpha 1 (I) collagen gene. Journal of Biological Chemistry 270: 3400–3408. [PubMed: 7852426]
    134.
    Hildebrandt M. and Nellen W. (1992) Differential antisense transcription from the Dictyostelium EB4 gene locus: Implications on antisense-mediated regulation of mRNA stability. Cell 69: 197–204. [PubMed: 1555240]
    135.
    Lagrutta A.A., McCarthy J.G., Scherczinger C.A. and Heywood S.M. (1989) Identification and developmental expression of a novel embryonic myosin heavy-chain gene in chicken. DNA 8: 39–50. [PubMed: 2707122]
    136.
    Rogers J.C. (1988) RNA complementary to α-amylase mRNA in barley. Plant Molecular Biology 11: 125–138. [PubMed: 24272255]
    137.
    Schulz R.A. and Butler B.A. (1989) Overlapping genes of Drosophila melanogaster: Organization of the z600-gonadal-Eip28/29 gene cluster. Genes & Development 3: 232–242. [PubMed: 2497054]
    138.
    Miyajima N. et al. (1989) Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell 57: 31–39. [PubMed: 2539258]
    139.
    Eveleth D.D. and Marsh J.L. (1987) Overlapping transcription units in Drosophila: Sequence and structure of the Cs gene. Molecular and General Genetics 209: 290–298. [PubMed: 3478553]
    140.
    Potts J.D., Vincent E.B., Runyan R.B. and Weeks D.L. (1992) Sense and antisense TGF beta 3 mRNA levels correlate with cardiac valve induction. Developmental Dynamics 193: 340–345. [PubMed: 1511174]
    141.
    Werner A. (2005) Natural antisense transcripts. RNA Biology 2: 53–62. [PubMed: 17132938]
    142.
    Engstrom P.G. et al. (2006) Complex loci in human and mouse genomes. PLOS Genetics 2: e47. [PMC free article: PMC1449890] [PubMed: 16683030]
    143.
    Ashe H.L., Monks J., Wijgerde M., Fraser P. and Proudfoot N.J. (1997) Intergenic transcription and transinduction of the human beta-globin locus. Genes & Development 11: 2494–2509. [PMC free article: PMC316561] [PubMed: 9334315]
    144.
    Kong S., Bohl D., Li C. and Tuan D. (1997) Transcription of the HS2 enhancer toward a cis-linked gene is independent of the orientation, position, and distance of the enhancer relative to the gene. Molecular and Cellular Biology 17: 3955–3965. [PMC free article: PMC232248] [PubMed: 9199330]
    145.
    Adelman J.P., Bond C.T., Douglass J. and Herbert E. (1987) Two mammalian genes transcribed from opposite strands of the same DNA locus. Science 235: 1514–1517. [PubMed: 3547652]
    146.
    Lewis E.B. (1978) A gene complex controlling segmentation in Drosophila. Nature 276: 565–570. [PubMed: 103000]
    147.
    Akam M.E., Martinez-Arias A., Weinzierl R. and Wilde C.D. (1985) Function and expression of ultrabithorax in the Drosophila embryo. Cold Spring Harbor Symposia on Quantitative Biology 50: 195–200. [PubMed: 3868478]
    148.
    Hogness D.S. et al. (1985) Regulation and products of the Ubx domain of the bithorax complex. Cold Spring Harbor Symposia on Quantitative Biology 50: 181–194. [PubMed: 3938361]
    149.
    Lipshitz H.D., Peattie D.A. and Hogness D.S. (1987) Novel transcripts from the Ultrabithorax domain of the bithorax complex. Genes & Development 1: 307–322. [PubMed: 3119423]
    150.
    Garaulet D. and Lai E. (2015) Hox miRNA regulation within the Drosophila Bithorax Complex: Patterning behavior. Mechanisms of Development 138: 151–159. [PMC free article: PMC4673027] [PubMed: 26311219]
    151.
    Sanchez-Herrero E. and Akam M. (1989) Spatially ordered transcription of regulatory DNA in the bithorax complex of Drosophila. Development 107: 321–329. [PubMed: 2632227]
    152.
    Cumberledge S., Zaratzian A. and Sakonju S. (1990) Characterization of two RNAs transcribed from the cis-regulatory region of the abd-A domain within the Drosophila bithorax complex. Proceedings of the National Academy of Sciences USA 87: 3259–3263. [PMC free article: PMC53879] [PubMed: 1692133]
    153.
    Kornienko A.E., Guenzl P.M., Barlow D.P. and Pauler F.M. (2013) Gene regulation by the act of long non-coding RNA transcription. BMC Biology 11: 59. [PMC free article: PMC3668284] [PubMed: 23721193]
    154.
    Li W., Notani D. and Rosenfeld M.G. (2016) Enhancers as non-coding RNA transcription units: Recent insights and future perspectives. Nature Reviews Genetics 17: 207–223. [PubMed: 26948815]
    155.
    Tillib S. et al. (1999) Trithorax- and Polycomb-group response elements within an Ultrabithorax transcription maintenance unit consist of closely situated but separable sequences. Molecular and Cellular Biology 19: 5189–5202. [PMC free article: PMC84362] [PubMed: 10373568]
    156.
    Zhou J., Ashe H., Burks C. and Levine M. (1999) Characterization of the transvection mediating region of the abdominal-B locus in Drosophila. Development 126: 3057–3065. [PubMed: 10375498]
    157.
    Maeda R.K. and Karch F. (2006) The ABC of the BX-C: The bithorax complex explained. Development 133: 1413–1422. [PubMed: 16556913]
    158.
    Garbe J.C. and Pardue M.L. (1986) Heat shock locus 93D of Drosophila melanogaster: A spliced RNA most strongly conserved in the intron sequence. Proceedings of the National Academy of Sciences USA 83: 1812–1816. [PMC free article: PMC323174] [PubMed: 3081901]
    159.
    Lakhotia S.C. and Mukherjee T. (1982) Absence of novel translation products in relation to induced activity of the 93D puff in Drosophila melanogaster. Chromosoma 85: 369–374. [PubMed: 6811224]
    160.
    Garbe J.C., Bendena W.G., Alfano M. and Pardue M.L. (1986) A Drosophila heat shock locus with a rapidly diverging sequence but a conserved structure. Journal of Biological Chemistry 261: 16889–16894. [PubMed: 3097014]
    161.
    Fini M.E., Bendena W.G. and Pardue M.L. (1989) Unusual behavior of the cytoplasmic transcript of hsr omega: An abundant, stress-inducible RNA that is translated but yields no detectable protein product. Journal of Cell Biology 108: 2045–2057. [PMC free article: PMC2115576] [PubMed: 2500443]
    162.
    Bendena W.G., Ayme-Southgate A., Garbe J.C. and Pardue M.L. (1991) Expression of heat-shock locus hsr-omega in nonstressed cells during development in Drosophila melanogaster. Developmental Biology 144: 65–77. [PubMed: 1704862]
    163.
    Lakhotia S.C. and Sharma A. (1996) The 93D (hsr-omega) locus of Drosophila: Non-coding gene with house-keeping functions. Genetica 97: 339–348. [PubMed: 9081862]
    164.
    Prasanth K.V., Rajendra T.K., Lal A.K. and Lakhotia S.C. (2000) Omega speckles - a novel class of nuclear speckles containing hnRNPs associated with noncoding hsr-omega RNA in Drosophila. Journal of Cell Science 113: 3485–3497. [PubMed: 10984439]
    165.
    Kemp D.J., Harris A.W. and Adams J.M. (1980) Transcripts of the immunoglobulin C mu gene vary in structure and splicing during lymphoid development. Proceedings of the National Academy of Sciences USA 77: 7400–7404. [PMC free article: PMC350511] [PubMed: 6784123]
    166.
    Lennon G.G. and Perry R.P. (1985) Cμ-containing transcripts initiate heterogeneously within the IgH enhancer region and contain a novel 5′-nontranslatable exon. Nature 318: 475–478. [PubMed: 3934561]
    167.
    Yancopoulos G.D. and Alt F.W. (1985) Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell 40: 271–281. [PubMed: 2578321]
    168.
    Reaban M.E. and Griffin J.A. (1990) Induction of RNA-stabilized DMA conformers by transcription of an immunoglobulin switch region. Nature 348: 342–344. [PubMed: 1701219]
    169.
    Bolland D.J. et al. (2004) Antisense intergenic transcription in V(D)J recombination. Nature Immunology 5: 630–637. [PubMed: 15107847]
    170.
    Abarrategui I. and Krangel M.S. (2007) Noncoding transcription controls downstream promoters to regulate T-cell receptor alpha recombination. EMBO Journal 26: 4380–4390. [PMC free article: PMC2034674] [PubMed: 17882258]
    171.
    Yewdell W.T. and Chaudhuri J. (2017) A transcriptional serenAID: The role of noncoding RNAs in class switch recombination. International Immunology 29: 183–196. [PMC free article: PMC5890902] [PubMed: 28535205]
    172.
    Rothschild G. et al. (2020) Noncoding RNA transcription alters chromosomal topology to promote isotype-specific class switch recombination. Science Immunology 5: eaay5864. [PMC free article: PMC7608691] [PubMed: 32034089]
    173.
    Calzone F.J., Lee J.J., Le N Britten R.J. and Davidson E.H. (1988) A long, nontranslatable poly(A) RNA stored in the egg of the sea urchin Strongylocentrotus purpuratus. Genes & Development 2: 305–318. [PubMed: 2454211]
    174.
    Cory S., Graham M., Webb E., Corcoran L. and Adams J.M. (1985) Variant (6;15) translocations in murine plasmacytomas involve a chromosome 15 locus at least 72 kb from the c-myc oncogene. EMBO Journal 4: 675–681. [PMC free article: PMC554241] [PubMed: 3924592]
    175.
    Graham M. and Adams J.M. (1986) Chromosome 8 breakpoint far 3′ of the c-myc oncogene in a Burkitt’s lymphoma 2;8 variant translocation is equivalent to the murine pvt-1 locus. EMBO Journal 5: 2845–2851. [PMC free article: PMC1167233] [PubMed: 3024964]
    176.
    Shtivelman E., Henglein B., Groitl P., Lipp M. and Bishop J.M. (1989) Identification of a human transcription unit affected by the variant chromosomal translocations 2;8 and 8;22 of Burkitt lymphoma. Proceedings of the National Academy of Sciences USA 86: 3257–3260. [PMC free article: PMC287109] [PubMed: 2470097]
    177.
    Shtivelman E. and Bishop J.M. (1989) The PVT gene frequently amplifies with MYC in tumor cells. Molecular and Cellular Biology 9: 1148–1154. [PMC free article: PMC362705] [PubMed: 2725491]
    178.
    Shtivelman E. and Bishop J.M. (1990) Effects of translocations on transcription from PVT. Molecular and Cellular Biology 10: 1835–1839. [PMC free article: PMC362296] [PubMed: 2181290]
    179.
    Huppi K., Pitt J., Wahlberg B. and Caplen N. (2012) The 8q24 gene desert: An oasis of non-coding transcriptional activity. Frontiers in Genetics 3: 69. [PMC free article: PMC3339310] [PubMed: 22558003]
    180.
    Tseng Y.-Y. et al. (2014) PVT1 dependence in cancer with MYC copy-number increase. Nature 512: 82–86. [PMC free article: PMC4767149] [PubMed: 25043044]
    181.
    Tolomeo D., Agostini A., Visci G., Traversa D. and Tiziana Storlazzi C. (2021) PVT1: A long non-coding RNA recurrently involved in neoplasia-associated fusion transcripts. Gene 779: 145497. [PubMed: 33600954]
    182.
    Tam W., Ben-Yehuda D. and Hayward W.S. (1997) bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its noncoding RNA. Molecular and Cellular Biology 17: 1490–1502. [PMC free article: PMC231875] [PubMed: 9032277]
    183.
    Tam W. (2001) Identification and characterization of human BIC, a gene on chromosome 21 that encodes a noncoding RNA. Gene 274: 157–167. [PubMed: 11675008]
    184.
    Eis P.S. et al. (2005) Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proceedings of the National Academy of Sciences USA 102: 3627–3632. [PMC free article: PMC552785] [PubMed: 15738415]
    185.
    Tam W. and Dahlberg J.E. (2006) miR-155/BIC as an oncogenic microRNA. Genes Chromosomes Cancer 45: 211–212. [PubMed: 16252262]
    186.
    Takei Y., Ishikawa S., Tokino T., Muto T. and Nakamura Y. (1998) Isolation of a novel TP53 target gene from a colon cancer cell line carrying a highly regulated wild-type TP53 expression system. Genes, Chromosomes and Cancer 23: 1–9. [PubMed: 9713990]
    187.
    Diaz-Lagares A. et al. (2016) Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer. Proceedings of the National Academy of Sciences USA 113: E7535–44. [PMC free article: PMC5127373] [PubMed: 27821766]
    188.
    Bussemakers M.J. et al. (1999) DD3: A new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Research 59: 5975–5979. [PubMed: 10606244]
    189.
    Lee G.L., Dobi A. and Srivastava S. (2011) Diagnostic performance of the PCA3 urine test. Nature Reviews Urology 8: 123–124. [PubMed: 21394175]
    190.
    Beck-Engeser G.B. et al. (2008) Pvt1-encoded microRNAs in oncogenesis. Retrovirology 5: 4. [PMC free article: PMC2257975] [PubMed: 18194563]
    191.
    Velleca M.A., Wallace M.C. and Merlie J.P. (1994) A novel synapse-associated noncoding RNA. Molecular and Cellular Biology 14: 7095–7104. [PMC free article: PMC359243] [PubMed: 7523860]
    192.
    Rodriguez A., Griffiths-Jones S., Ashurst J.L. and Bradley A. (2004) Identification of mammalian microRNA host genes and transcription units. Genome Research 14: 1902–1910. [PMC free article: PMC524413] [PubMed: 15364901]
    193.
    Brannan C.I., Dees E.C., Ingram R.S. and Tilghman S.M. (1990) The product of the H19 gene may function as an RNA. Molecular and Cellular Biology 10: 28–36. [PMC free article: PMC360709] [PubMed: 1688465]
    194.
    Leibovitch M.P. et al. (1991) The human ASM (Adult Skeletal Muscle) gene expression and chromosomal assignment to 11p15. Biochemical and Biophysical Research Communications 180: 1241–1250. [PubMed: 1953776]
    195.
    Gascoigne D.K. et al. (2012) Pinstripe: A suite of programs for integrating transcriptomic and proteomic datasets identifies novel proteins and improves differentiation of protein-coding and non-coding genes. Bioinformatics 28: 3042–3050. [PubMed: 23044541]
    196.
    Bartolomei M.S., Zemel S. and Tilghman S.M. (1991) Parental imprinting of the mouse H19 gene. Nature 351: 153–155. [PubMed: 1709450]
    197.
    Hao Y., Crenshaw T., Moulton T., Newcomb E. and Tycko B. (1993) Tumour-suppressor activity of H19 RNA. Nature 365: 764–767. [PubMed: 7692308]
    198.
    Leighton P.A., Ingram R.S., Eggenschwiler J., Efstratiadis A. and Tilghman S.M. (1995) Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375: 34–39. [PubMed: 7536897]
    199.
    Wrana J.L. (1994) H19, a tumour suppressing RNA? BioEssays 16: 89–90. [PubMed: 8147848]
    200.
    Forné T. et al. (1997) Loss of the maternal H19 gene induces changes in Igf2 methylation in both cis and trans. Proceedings of the National Academy of Sciences USA 94: 10243–10248. [PMC free article: PMC23347] [PubMed: 9294195]
    201.
    Hur S.K. et al. (2016) Humanized H19/Igf2 locus reveals diverged imprinting mechanism between mouse and human and reflects Silver–Russell syndrome phenotypes. Proceedings of the National Academy of Sciences USA 113: 10938–10943. [PMC free article: PMC5047210] [PubMed: 27621468]
    202.
    Brunkow M.E. and Tilghman S.M. (1991) Ectopic expression of the H19 gene in mice causes prenatal lethality. Genes & Development 5: 1092–1101. [PubMed: 2044956]
    203.
    Brown C.J. et al. (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349: 38–44. [PubMed: 1985261]
    204.
    Brown C.J. et al. (1992) The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71: 527–542. [PubMed: 1423611]
    205.
    Clemson C.M., McNeil J.A., Willard H.F. and Lawrence J.B. (1996) XIST RNA paints the inactive X chromosome at interphase: Evidence for a novel RNA involved in nuclear/chromosome structure. Journal of Cell Biology 132: 259–275. [PMC free article: PMC2120729] [PubMed: 8636206]
    206.
    Hall L.L. and Lawrence J.B. (2003) The cell biology of a novel chromosomal RNA: Chromosome painting by XIST/Xist RNA initiates a remodeling cascade. Seminars in Cell & Developmental Biology 14: 369–378. [PubMed: 15015744]
    207.
    Chaumeil J., Le Baccon P., Wutz A. and Heard E. (2006) A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes & Development 20: 2223–2237. [PMC free article: PMC1553206] [PubMed: 16912274]
    208.
    Wutz A. (2011) Gene silencing in X-chromosome inactivation: Advances in understanding facultative heterochromatin formation. Nature Reviews Genetics 12: 542–553. [PubMed: 21765457]
    209.
    Galupa R. and Heard E. (2018) X-chromosome inactivation: A crossroads between chromosome architecture and gene regulation. Annual Review of Genetics 52: 535–566. [PubMed: 30256677]
    210.
    Heard E. and Disteche C.M. (2006) Dosage compensation in mammals: Fine-tuning the expression of the X chromosome. Genes & Development 20: 1848–1867. [PubMed: 16847345]
    211.
    Fan G. and Tran J. (2011) X chromosome inactivation in human and mouse pluripotent stem cells. Human Genetics 130: 217–222. [PMC free article: PMC3965368] [PubMed: 21678064]
    212.
    Duret L., Chureau C., Samain S., Weissenbach J. and Avner P. (2006) The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science 312: 1653–1655. [PubMed: 16778056]
    213.
    Elisaphenko E.A. et al. (2008) A dual origin of the Xist gene from a protein-coding gene and a set of transposable elements. PLOS ONE 3: e2521. [PMC free article: PMC2430539] [PubMed: 18575625]
    214.
    Meller V.H., Wu K.H., Roman G., Kuroda M.I. and Davis R.L. (1997) roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system. Cell 88: 445–457. [PubMed: 9038336]
    215.
    Kelley R.L. et al. (1999) Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Cell 98: 513–522. [PubMed: 10481915]
    216.
    Meller V.H. (2003) Initiation of dosage compensation in Drosophila embryos depends on expression of the roX RNAs. Mechanisms of Development 120: 759–767. [PubMed: 12915227]
    217.
    Kelley R.L. and Kuroda M.I. (2003) The Drosophila roX1 RNA gene can overcome silent chromatin by recruiting the male-specific lethal dosage compensation complex. Genetics 164: 565–574. [PMC free article: PMC1462573] [PubMed: 12807777]
    218.
    Park Y., Oh H., Meller V.H. and Kuroda M.I. (2005) Variable splicing of non-coding roX2 RNAs influences targeting of MSL dosage compensation complexes in Drosophila. RNA Biology 2: 157–164. [PubMed: 17114930]
    219.
    Ilik I.A. et al. (2013) Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila. Molecular Cell 51: 156–173. [PMC free article: PMC3804161] [PubMed: 23870142]
    220.
    Akhtar A., Zink D. and Becker P.B. (2000) Chromodomains are protein-RNA interaction modules. Nature 407: 405–409. [PubMed: 11014199]
    221.
    Akhtar A. (2003) Dosage compensation: An intertwined world of RNA and chromatin remodelling. Current Opinion in Genetics and Development 13: 161–169. [PubMed: 12672493]
    222.
    Valsecchi C.I.K. et al. (2020) RNA nucleation by MSL2 induces selective X chromosome compartmentalization. Nature 589: 137–142. [PubMed: 33208948]
    223.
    Erdmann V.A., Szymanski M., Hochberg A., de Groot N. and Barciszewski J. (1999) Collection of mRNA-like non-coding RNAs. Nucleic Acids Research 27: 192–195. [PMC free article: PMC148132] [PubMed: 9847177]
    224.
    Erdmann V.A., Szymanski M., Hochberg A., Groot N. and Barciszewski J. (2000) Non-coding, mRNA-like RNAs database Y2K. Nucleic Acids Research 28: 197–200. [PMC free article: PMC102406] [PubMed: 10592224]
    225.
    Watanabe Y. and Yamamoto M. (1994) S. pombe mei2+ encodes an RNA-binding protein essential for premeiotic DNA synthesis and meiosis I, which cooperates with a novel RNA species meiRNA. Cell 78: 487–498. [PubMed: 7520368]
    226.
    Ding D.Q. et al. (2012) Meiosis-specific noncoding RNA mediates robust pairing of homologous chromosomes in meiosis. Science 336: 732–736. [PubMed: 22582262]
    227.
    Hiraoka Y. (2020) Phase separation drives pairing of homologous chromosomes. Current Genetics 66: 881–887. [PubMed: 32285141]
    228.
    Kumimoto H., Yoshida H. and Okamoto K. (1995) RNA polymerase II transcribes Dictyostelium untranslatable gene, dutA, specifically in the developmental phase. Biochemical and Biophysical Research Communications 216: 273–278. [PubMed: 7488100]
    229.
    Kumimoto H., Yoshida H. and Okamoto K. (1996) Expression of Dictyostelium early gene, dutA, is independent of cAMP pulses but dependent on protein kinase A. FEMS Microbiology Letters 140: 121–124. [PubMed: 8764472]
    230.
    Yoshida H., Kumimoto H. and Okamoto K. (1994) dutA RNA functions as an untranslatable RNA in the development of Dictyostelium discoideum. Nucleic Acids Research 22: 41–46. [PMC free article: PMC307743] [PubMed: 8127653]
    231.
    Su X.Z. et al. (1995) The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82: 89–100. [PubMed: 7606788]
    232.
    Crespi M.D. et al. (1994) enod40, a gene expressed during nodule organogenesis, codes for a non-translatable RNA involved in plant growth. EMBO Journal 13: 5099–112. [PMC free article: PMC395456] [PubMed: 7957074]
    233.
    Campalans A., Kondorosi A. and Crespi M. (2004) Enod40, a short open reading frame-containing mRNA, induces cytoplasmic localization of a nuclear RNA binding protein in Medicago truncatula. Plant Cell 16: 1047–1059. [PMC free article: PMC412876] [PubMed: 15037734]
    234.
    Gultyaev A.P. and Roussis A. (2007) Identification of conserved secondary structures and expansion segments in enod40 RNAs reveals new enod40 homologues in plants. Nucleic Acids Research 35: 3144–3152. [PMC free article: PMC1888808] [PubMed: 17452360]
    235.
    Zhou B.-S., Beidler D.R. and Cheng Y.-C. (1992) Identification of antisense RNA transcripts from a human DNA topoisomerase I pseudogene. Cancer Research 52: 4280–4285. [PubMed: 1339303]
    236.
    Korneev S.A., Park J.H. and O‘Shea M. (1999) Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. Journal of Neuroscience 19: 7711–7720. [PMC free article: PMC6782476] [PubMed: 10479675]
    237.
    Korneev S.A. et al. (2008) Novel noncoding antisense RNA transcribed from human anti-NOS2A locus is differentially regulated during neuronal differentiation of embryonic stem cells. RNA 14: 2030–2037. [PMC free article: PMC2553742] [PubMed: 18820242]
    238.
    Kloc M., Spohr G. and Etkin L.D. (1993) Translocation of repetitive RNA sequences with the germ plasm in Xenopus oocytes. Science 262: 1712–1714. [PubMed: 7505061]
    239.
    Kloc M. and Etkin L.D. (1994) Delocalization of Vg1 mRNA from the vegetal cortex in Xenopus oocytes after destruction of Xlsirt RNA. Science 265: 1101–1103. [PubMed: 7520603]
    240.
    Swalla B.J. and Jeffery W.R. (1995) A maternal RNA localized in the yellow crescent is segregated to the larval muscle cells during ascidian development. Developmental Biology 170: 353–364. [PubMed: 7544307]
    241.
    Swalla B.J. and Jeffery W.R. (1996) PCNA mRNA has a 3′UTR antisense to yellow crescent RNA and is localized in ascidian eggs and embryos. Developmental Biology 178: 23–34. [PubMed: 8812106]
    242.
    Coccia E.M. et al. (1992) Regulation and expression of a growth arrest-specific gene (gas5) during growth, differentiation, and development. Molecular and Cellular Biology 12: 3514–3521. [PMC free article: PMC364604] [PubMed: 1630459]
    243.
    Smith C.M. and Steitz J.A. (1998) Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5′-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Molecular and Cellular Biology 18: 6897–909. [PMC free article: PMC109273] [PubMed: 9819378]
    244.
    Raho G., Barone V., Rossi D., Philipson L. and Sorrentino V. (2000) The gas5 gene shows four alternative splicing patterns without coding for a protein. Gene 256: 13–17. [PubMed: 11054530]
    245.
    Sang L. et al. (2021) Mitochondrial long non-coding RNA GAS5 tunes TCA metabolism in response to nutrient stress. Nature Metabolism 3: 90–106. [PubMed: 33398195]
    246.
    Lanz R.B. et al. (1999) A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97: 17–27. [PubMed: 10199399]
    247.
    Lanz R.B., Razani B., Goldberg A.D. and O‘Malley B.W. (2002) Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proceedings of the National Academy of Sciences USA 99: 16081–16086. [PMC free article: PMC138568] [PubMed: 12444263]
    248.
    Ghosh S.K., Patton J.R. and Spanjaard R.A. (2012) A small RNA derived from RNA coactivator SRA blocks steroid receptor signaling via inhibition of Pus1p-mediated pseudouridylation of SRA: Evidence of a novel RNA binding domain in the N-terminus of steroid receptors. Biochemistry 51: 8163–8172. [PubMed: 22998747]
    249.
    Novikova I.V., Hennelly S.P. and Sanbonmatsu K.Y. (2012) Structural architecture of the human long non-coding RNA, steroid receptor RNA activator. Nucleic Acids Research 40: 5034–5051. [PMC free article: PMC3367176] [PubMed: 22362738]
    250.
    Sengupta D.J. et al. (1996) A three-hybrid system to detect RNA-protein interactions in vivo. Proceedings of the National Academy of Sciences USA 93: 8496–8501. [PMC free article: PMC38700] [PubMed: 8710898]
    251.
    Sengupta D.J., Wickens M. and Fields S. (1999) Identification of RNAs that bind to a specific protein using the yeast three-hybrid system. RNA 5: 596–601. [PMC free article: PMC1369785] [PubMed: 10199575]
    252.
    Saha S., Ansari A.Z., Jarrell K.A. and Ptashne M. (2003) RNA sequences that work as transcriptional activating regions. Nucleic Acids Research 31: 1565–1570. [PMC free article: PMC149820] [PubMed: 12595565]
    253.
    Hsieh-Li H.M. et al. (1995) Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. Development 121: 1373–1385. [PubMed: 7789268]
    254.
    Potter S.S. and Branford W.W. (1998) Evolutionary conservation and tissue-specific processing of Hoxa 11 antisense transcripts. Mammalian Genome 9: 799–806. [PubMed: 9745033]
    255.
    Bedford M., Arman E., Orr-Urtreger A. and Lonai P. (1995) Analysis of the Hoxd-3 gene: Structure and localization of its sense and natural antisense transcripts. DNA and Cell Biology 14: 295–304. [PubMed: 7710686]
    256.
    Liu J.K., Ghattas I., Liu S., Chen S. and Rubenstein J.L. (1997) Dlx genes encode DNA-binding proteins that are expressed in an overlapping and sequential pattern during basal ganglia differentiation. Developmental Dynamics 210: 498–512. [PubMed: 9415433]
    257.
    McGuinness T. et al. (1996) Sequence, organization, and transcription of the Dlx-1 and Dlx-2 locus. Genomics 35: 473–485. [PubMed: 8812481]
    258.
    Lee J.T., Davidow L.S. and Warshawsky D. (1999) Tsix, a gene antisense to Xist at the X-inactivation centre. Nature Genetics 21: 400–404. [PubMed: 10192391]
    259.
    Lee J.T., Lu N. and Han Y. (1999) Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain. Proceedings of the National Academy of Sciences USA 96: 3836–3841. [PMC free article: PMC22381] [PubMed: 10097124]
    260.
    Moore T. et al. (1997) Multiple imprinted sense and antisense transcripts, differential methylation and tandem repeats in a putative imprinting control region upstream of mouse Igf2. Proceedings of the National Academy of Sciences USA 94: 12509–12514. [PMC free article: PMC25020] [PubMed: 9356480]
    261.
    Ainscough J.F., Koide T., Tada M., Barton S. and Surani M.A. (1997) Imprinting Cof Igf2 and H19 from a 130 kb YAC transgene. Development 124: 3621–3632. [PubMed: 9342054]
    262.
    Rougeulle C., Cardoso C., Fontes M., Colleaux L. and Lalande M. (1998) An imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript. Nature Genetics 19: 15–16. [PubMed: 9590281]
    263.
    Smith R.J., Dean W., Konfortova G. and Kelsey G. (2003) Identification of novel imprinted genes in a genome-wide screen for maternal methylation. Genome Research 13: 558–569. [PMC free article: PMC430166] [PubMed: 12670997]
    264.
    Schoenfelder S., Smits G., Fraser P., Reik W. and Paro R. (2007) Non-coding transcripts in the H19 imprinting control region mediate gene silencing in transgenic Drosophila. EMBO Reports 8: 1068–1073. [PMC free article: PMC2247386] [PubMed: 17948025]
    265.
    Wutz A. et al. (1997) Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389: 745–749. [PubMed: 9338788]
    266.
    Lyle R. et al. (2000) The imprinted antisense RNA at the Igf2r locus overlaps but does not imprint Mas1. Nature Genetics 25: 19–21. [PubMed: 10802648]
    267.
    Stöger R. et al. (1993) Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell 73: 61–71. [PubMed: 8462104]
    268.
    Peters J. et al. (1999) A cluster of oppositely imprinted transcripts at the Gnas locus in the distal imprinting region of mouse chromosome 2. Proceedings of the National Academy of Sciences USA 96: 3830–3835. [PMC free article: PMC22380] [PubMed: 10097123]
    269.
    Kim J., Bergmann A., Wehri E., Lu X. and Stubbs L. (2001) Imprinting and evolution of two Kruppel-type zinc-finger genes, ZIM3 and ZNF264, located in the PEG3/USP29 imprinted domain. Genomics 77: 91–98. [PubMed: 11543637]
    270.
    Tierling S. et al. (2006) High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12. Genomics 87: 225–235. [PubMed: 16309881]
    271.
    Nesterova T.B., Barton S.C., Surani M.A. and Brockdorff N. (2001) Loss of Xist imprinting in diploid parthenogenetic preimplantation embryos. Developmental Biology 235: 343–350. [PubMed: 11437441]
    272.
    Miyoshi N. et al. (2000) Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes to Cells 5: 211–220. [PubMed: 10759892]
    273.
    Schuster-Gossler K., Simon-Chazottes D., Guenet J.L., Zachgo J. and Gossler A. (1996) Gtl2lacZ, an insertional mutation on mouse chromosome 12 with parental origin-dependent phenotype. Mammalian Genome 7: 20–24. [PubMed: 8903723]
    274.
    Schuster-Gossler K., Bilinski P., Sado T., Ferguson-Smith A. and Gossler A. (1998) The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA. Developmental Dynamics 212: 214–228. [PubMed: 9626496]
    275.
    Smilinich N.J. et al. (1999) A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. Proceedings of the National Academy of Sciences USA 96: 8064–8069. [PMC free article: PMC22188] [PubMed: 10393948]
    276.
    Thakur N. et al. (2004) An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region. Molecular and Cellular Biology 24: 7855–7862. [PMC free article: PMC515059] [PubMed: 15340049]
    277.
    Mancini-Dinardo D., Steele S.J., Levorse J.M., Ingram R.S. and Tilghman S.M. (2006) Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes & Development 20: 1268–1282. [PMC free article: PMC1472902] [PubMed: 16702402]
    278.
    Pandey R.R. et al. (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Molecular Cell 32: 232–246. [PubMed: 18951091]
    279.
    Kanduri C. (2011) Kcnq1ot1: A chromatin regulatory RNA. Seminars in Cell & Developmental Biology 22: 343–350. [PubMed: 21345374]
    280.
    Reik W. and Constancia M. (1997) Genomic imprinting. Making sense or antisense? Nature 389: 669–671. [PubMed: 9338773]
    281.
    Sleutels F., Zwart R. and Barlow D.P. (2002) The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 415: 810–813. [PubMed: 11845212]
    282.
    Nagano T. et al. (2008) The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322: 1717–1720. [PubMed: 18988810]
    283.
    Mohammad F., Mondal T., Guseva N., Pandey G.K. and Kanduri C. (2010) Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development 137: 2493–2499. [PubMed: 20573698]
    284.
    Deveson I.W. et al. (2018) Universal alternative splicing of noncoding exons. Cell Systems 6: 245–255. [PubMed: 29396323]
    285.
    Mazumder B., Seshadri V. and Fox P.L. (2003) Translational control by the 3′-UTR: The ends specify the means. Trends in Biochemical Sciences 28: 91–98. [PubMed: 12575997]
    286.
    Siepel A. et al. (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Research 15: 1034–1050. [PMC free article: PMC1182216] [PubMed: 16024819]
    287.
    Chen C.-Y., Chen S.-T., Juan H.-F. and Huang H.-C. (2012) Lengthening of 3′UTR increases with morphological complexity in animal evolution. Bioinformatics 28: 3178–3181. [PubMed: 23080117]
    288.
    Mayr C. (2016) Evolution and biological roles of alternative 3′UTRs. Trends in Cell Biology 26: 227–237. [PMC free article: PMC4955613] [PubMed: 26597575]
    289.
    Mayr C. (2017) Regulation by 3′-untranslated regions. Annual Review of Genetics 51: 171–194. [PubMed: 28853924]
    290.
    Rastinejad F., Conboy M.J., Rando T.A. and Blau H.M. (1993) Tumor suppression by RNA from the 3′ untranslated region of alpha-tropomyosin. Cell 75: 1107–1117. [PubMed: 7505203]
    291.
    Rastinejad F. and Blau H.M. (1993) Genetic complementation reveals a novel regulatory role for 3′ untranslated regions in growth and differentiation. Cell 72: 903–917. [PubMed: 8384533]
    292.
    Fan H., Villegas C., Huang A. and Wright J.A. (1996) Suppression of malignancy by the 3′ untranslated regions of ribonucleotide reductase R1 and R2 messenger RNAs. Cancer Research 56: 4366–4369. [PubMed: 8813126]
    293.
    Jupe E.R., Liu X.T., Kiehlbauch J.L., McClung J.K. and Dell’Orco R.T. (1996) Prohibitin in breast cancer cell lines: Loss of antiproliferative activity is linked to 3′ untranslated region mutations. Cell Growth and Differentiation 7: 871–878. [PubMed: 8809404]
    294.
    Jenny A. et al. (2006) A translation-independent role of oskar RNA in early Drosophila oogenesis. Development 133: 2827–2833. [PubMed: 16835436]
    295.
    Mercer T.R. et al. (2011) Expression of distinct RNAs from 3′ untranslated regions. Nucleic Acids Research 39: 2393–2403. [PMC free article: PMC3064787] [PubMed: 21075793]
    296.
    Miura P., Shenker S., Andreu-Agullo C., Westholm J.O. and Lai E.C. (2013) Widespread and extensive lengthening of 3′ UTRs in the mammalian brain. Genome Research 23: 812–825. [PMC free article: PMC3638137] [PubMed: 23520388]
    297.
    Kocabas A., Duarte T., Kumar S. and Hynes M.A. (2015) Widespread differential expression of coding region and 3′UTR sequences in neurons and other tissues. Neuron 88: 1149–1156. [PubMed: 26687222]
    298.
    Vilborg A., Passarelli M.C., Yario T.A., Tycowski K.T. and Steitz J.A. (2015) Widespread inducible transcription downstream of human genes. Molecular Cell 59: 449–461. [PMC free article: PMC4530028] [PubMed: 26190259]
    299.
    Malka Y. et al. (2017) Post-transcriptional 3′-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments. Nature Communications 8: 2029. [PMC free article: PMC5725528] [PubMed: 29229900]
    300.
    Sun H.-X., Li Y., Niu Q.-W. and Chua N.-H. (2017) Dehydration stress extends mRNA 3′ untranslated regions with noncoding RNA functions in Arabidopsis. Genome Research 27: 1427–1436. [PMC free article: PMC5538558] [PubMed: 28522613]
    301.
    Jeyapalan Z. et al. (2011) Expression of CD44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis. Nucleic Acids Research 39: 3026–3041. [PMC free article: PMC3082902] [PubMed: 21149267]
    302.
    Vilborg A. and Steitz J.A. (2017) Readthrough transcription: How are DoGs made and what do they do? RNA Biology 14: 632–636. [PMC free article: PMC5449079] [PubMed: 26861889]
    303.
    Andreassi C. et al. (2021) Cytoplasmic cleavage of IMPA1 3′ UTR is necessary for maintaining axon integrity. Cell Reports 34: 108778. [PMC free article: PMC7918530] [PubMed: 33626357]
    304.
    Lee R.C., Feinbaum R.L. and Ambros V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843–854. [PubMed: 8252621]
    305.
    Wightman B., Ha I. and Ruvkun G. (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75: 855–862. [PubMed: 8252622]
    306.
    Ruvkun G., Wightman B. and Ha I. (2004) The 20 years it took to recognize the importance of tiny RNAs. Cell 116: S93–6. [PubMed: 15055593]
    307.
    Ambros V. (2008) The evolution of our thinking about microRNAs. Nature Medicine 14: 1036–1040. [PubMed: 18841144]
    308.
    Olsen P.H. and Ambros V. (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology 216: 671–680. [PubMed: 10642801]
    309.
    Lee R., Feinbaum R. and Ambros V. (2004) A short history of a short RNA. Cell 116: S89–92. [PubMed: 15055592]
    310.
    Holley R.W. et al. (1965) Structure of a ribonucleic acid. Science 147: 1462–1465. [PubMed: 14263761]
    311.
    Wickens M. and Takayama K. (1994) RNA. Deviants - or emissaries. Nature 367: 17–18. [PubMed: 7509036]
    312.
    Nowak R. (1994) Mining treasures from ‘junk DNA’. Science 263: 608–610. [PubMed: 7508142]

    Chapter 10

    1.
    Smith C., Econome J., Schutt A., Klco S. and Cantor C. (1987) A physical map of the Escherichia coli K12 genome. Science 236: 1448–1453. [PubMed: 3296194]
    2.
    Römling U., Grothues D., Bautsch W. and Tümmler B. (1989) A physical genome map of Pseudomonas aeruginosa PAO. EMBO Journal 8: 4081–4089. [PMC free article: PMC401585] [PubMed: 2512121]
    3.
    Link A.J. and Olson M.V. (1991) Physical map of the Saccharomyces cerevisiae genome at 110-kilobase resolution. Genetics 127: 681–698. [PMC free article: PMC1204396] [PubMed: 2029969]
    4.
    Yanofsky M.F. et al. (1990) The protein encoded by the Arabidopsis homeotic gene agamous resembles transcription factors. Nature 346: 35–39. [PubMed: 1973265]
    5.
    Wensink P.C., Finnegan D.J., Donelson J.E. and Hogness D.S. (1974) A system for mapping DNA sequences in the chromosomes of Drosophila melanogaster. Cell 3: 315–325. [PubMed: 4216403]
    6.
    Grunstein M. and Hogness D.S. (1975) Colony hybridization: A method for the isolation of cloned DNAs that contain a specific gene. Proceedings of the National Academy of Sciences USA 72: 3961–3965. [PMC free article: PMC433117] [PubMed: 1105573]
    7.
    Bender W., Spierer P., Hogness D.S. and Chambon P. (1983) Chromosomal walking and jumping to isolate DNA from the Ace and rosy loci and the bithorax complex in Drosophila melanogaster. Journal of Molecular Biology 168: 17–33. [PubMed: 6410077]
    8.
    Bender W. et al. (1983) Molecular genetics of the bithorax complex in Drosophila melanogaster. Science 221: 23–29. [PubMed: 17737996]
    9.
    Rubin G.M. and Lewis E.B. (2000) A brief history of Drosophila’s contributions to genome research. Science 287: 2216–2218. [PubMed: 10731135]
    10.
    Nüsslein-Volhard C. and Wieschaus E. (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287: 795–801. [PubMed: 6776413]
    11.
    Bingham P.M., Levis R. and Rubin G.M. (1981) Cloning of DNA sequences from the white locus of D. melanogaster by a novel and general method. Cell 25: 693–704. [PubMed: 6269753]
    12.
    Cooley L., Kelley R. and Spradling A. (1988) Insertional mutagenesis of the Drosophila genome with single P elements. Science 239: 1121–1128. [PubMed: 2830671]
    13.
    Robertson E., Bradley A., Kuehn M. and Evans M. (1986) Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature 323: 445–448. [PubMed: 3762693]
    14.
    Folger K.R., Wong E.A., Wahl G. and Capecchi M.R. (1982) Patterns of integration of DNA microinjected into cultured mammalian cells: Evidence for homologous recombination between injected plasmid DNA molecules. Molecular and Cellular Biology 2: 1372–1387. [PMC free article: PMC369942] [PubMed: 6298598]
    15.
    Mansour S.L., Thomas K.R. and Capecchi M.R. (1988) Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes. Nature 336: 348–352. [PubMed: 3194019]
    16.
    Kuehn M.R., Bradley A., Robertson E.J. and Evans M.J. (1987) A potential animal model for Lesch–Nyhan syndrome through introduction of HPRT mutations into mice. Nature 326: 295–298. [PubMed: 3029599]
    17.
    Koller B.H. et al. (1989) Germ-line transmission of a planned alteration made in a hypoxanthine phosphoribosyltransferase gene by homologous recombination in embryonic stem cells. Proceedings of the National Academy of Sciences USA 86: 8927–8931. [PMC free article: PMC298403] [PubMed: 2573070]
    18.
    Smithies O., Gregg R.G., Boggs S.S., Koralewski M.A. and Kucherlapati R.S. (1985) Insertion of DNA sequences into the human chromosomal β-globin locus by homologous recombination. Nature 317: 230–234. [PubMed: 2995814]
    19.
    Thomas K.R. and Capecchi M.R. (1990) Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature 346: 847–850. [PubMed: 2202907]
    20.
    Thompson S., Clarke A.R., Pow A.M., Hooper M.L. and Melton D.W. (1989) Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells. Cell 56: 313–321. [PubMed: 2912572]
    21.
    Schwartzberg P.L., Goff S.P. and Robertson E.J. (1989) Germ-line transmission of a c-abl mutation produced by targeted gene disruption in ES cells. Science 246: 799–803. [PubMed: 2554496]
    22.
    O’Kane C.J. and Gehring W.J. (1987) Detection in situ of genomic regulatory elements in Drosophila. Proceedings of the National Academy of Sciences USA 84: 9123–9127. [PMC free article: PMC299704] [PubMed: 2827169]
    23.
    Brand A.H. and Perrimon N. (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401–415. [PubMed: 8223268]
    24.
    Anderson S. et al. (1981) Sequence and organization of the human mitochondrial genome. Nature 290: 457–465. [PubMed: 7219534]
    25.
    Shinozaki K. et al. (1986) The complete nucleotide sequence of the tobacco chloroplast genome: Its gene organization and expression. EMBO Journal 5: 2043–2049. [PMC free article: PMC1167080] [PubMed: 16453699]
    26.
    Smith L.M. et al. (1986) Fluorescence detection in automated DNA sequence analysis. Nature 321: 674–679. [PubMed: 3713851]
    27.
    Fleischmann R.D. et al. (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269: 496–512. [PubMed: 7542800]
    28.
    Adams M.D. et al. (1992) Sequence identification of 2,375 human brain genes. Nature 355: 632–634. [PubMed: 1538749]
    29.
    Blattner F.R. et al. (1997) The complete genome sequence of Escherichia coli K-12. Science 277: 1453–1462. [PubMed: 9278503]
    30.
    Andersson S.G.E. et al. (1998) The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396: 133–140. [PubMed: 9823893]
    31.
    Nakabachi A. et al. (2006) The 160-kilobase genome of the bacterial endosymbiont Carsonella. Science 314: 267. [PubMed: 17038615]
    32.
    Bennett G.M. and Moran N.A. (2013) Small, smaller, smallest: The origins and evolution of ancient dual symbioses in a phloem-feeding insect. Genome Biology and Evolution 5: 1675–1688. [PMC free article: PMC3787670] [PubMed: 23918810]
    33.
    Han K. et al. (2013) Extraordinary expansion of a Sorangium cellulosum genome from an alkaline milieu. Scientific Reports 3: 2101. [PMC free article: PMC3696898] [PubMed: 23812535]
    34.
    Land M. et al. (2015) Insights from 20 years of bacterial genome sequencing. Functional & Integrative Genomics 15: 141–161. [PMC free article: PMC4361730] [PubMed: 25722247]
    35.
    Hugenholtz P., Goebel B.M. and Pace N.R. (1998) Impact of culture-independent studies on the emerging phylogenetic view of bacterial diversity. Journal of Bacteriology 180: 4765–4774. [PMC free article: PMC107498] [PubMed: 9733676]
    36.
    Tyson G.W. et al. (2004) Community structure and metabolism through reconstruction of microbial genomes from the environment. Nature 428: 37–43. [PubMed: 14961025]
    37.
    Lukjancenko O., Wassenaar T.M. and Ussery D.W. (2010) Comparison of 61 sequenced Escherichia coli genomes. Microbial Ecology 60: 708–720. [PMC free article: PMC2974192] [PubMed: 20623278]
    38.
    Rouli L., Merhej V., Fournier P.E. and Raoult D. (2015) The bacterial pangenome as a new tool for analysing pathogenic bacteria. New Microbes and New Infections 7: 72–85. [PMC free article: PMC4552756] [PubMed: 26442149]
    39.
    Coelho L.P. et al. (2022) Towards the biogeography of prokaryotic genes. Nature 601: 252–256. [PMC free article: PMC7613196] [PubMed: 34912116]
    40.
    Pellicer J., Fay M.F. and Leitch I.J. (2010) The largest eukaryotic genome of them all? Botanical Journal of the Linnean Society 164: 10–15.
    41.
    Goffeau A. et al. (1996) Life with 6000 genes. Science 274: 546–567. [PubMed: 8849441]
    42.
    Mewes H.W. et al. (1997) Overview of the yeast genome. Nature 387: 7–8. [PubMed: 9169865]
    43.
    Zhang Z., Hesselberth J.R. and Fields S. (2007) Genome-wide identification of spliced introns using a tiling microarray. Genome Research 17: 503–509. [PMC free article: PMC1832097] [PubMed: 17351133]
    44.
    Parenteau J. et al. (2008) Deletion of many yeast introns reveals a minority of genes that require splicing for function. Molecular Biology of the Cell 19: 1932–1941. [PMC free article: PMC2366882] [PubMed: 18287520]
    45.
    Hayashi S., Mori S., Suzuki T., Suzuki T. and Yoshihisa T. (2019) Impact of intron removal from tRNA genes on Saccharomyces cerevisiae. Nucleic Acids Research 47: 5936–5949. [PMC free article: PMC6582322] [PubMed: 30997502]
    46.
    Parenteau J. et al. (2019) Introns are mediators of cell response to starvation. Nature 565: 612–617. [PubMed: 30651641]
    47.
    Morgan J.T., Fink G.R. and Bartel D.P. (2019) Excised linear introns regulate growth in yeast. Nature 565: 606–611. [PMC free article: PMC6464110] [PubMed: 30651636]
    48.
    Wood V. et al. (2002) The genome sequence of Schizosaccharomyces pombe. Nature 415: 871–880. [PubMed: 11859360]
    49.
    Botstein D., Chervitz S.A. and Cherry J.M. (1997) Yeast as a model organism. Science 277: 1259–1260. [PMC free article: PMC3039837] [PubMed: 9297238]
    50.
    Puddu F. et al. (2019) Genome architecture and stability in the Saccharomyces cerevisiae knockout collection. Nature 573: 416–420. [PMC free article: PMC6774800] [PubMed: 31511699]
    51.
    Bing J., Han P.-J., Liu W.-Q., Wang Q.-M. and Bai F.-Y. (2014) Evidence for a Far East Asian origin of lager beer yeast. Current Biology 24: R380–1. [PubMed: 24845661]
    52.
    Gallone B. et al. (2018) Origins, evolution, domestication and diversity of Saccharomyces beer yeasts. Current Opinion in Biotechnology 49: 148–155. [PubMed: 28869826]
    53.
    Galagan J.E. et al. (2003) The genome sequence of the filamentous fungus Neurospora crassa. Nature 422: 859–868. [PubMed: 12712197]
    54.
    Gardner M.J. et al. (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419: 498–511. [PMC free article: PMC3836256] [PubMed: 12368864]
    55.
    Holt R.A. et al. (2002) The genome sequence of the malaria mosquito Anopheles gambiae. Science 298: 129–149. [PubMed: 12364791]
    56.
    The C. elegans Sequencing Consortium (1998) Genome sequence of the nematode C. elegans: A platform for investigating biology. Science 282: 2012–2018. [PubMed: 9851916]
    57.
    Sulston J.E. and Horvitz H.R. (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental Biology 56: 110–156. [PubMed: 838129]
    58.
    Check E. (2002) Worm cast in starring role for Nobel prize. Nature 419: 548. [PubMed: 12374942]
    59.
    Feng Z. et al. (2006) A C. elegans model of nicotine-dependent behavior: Regulation by TRP-family channels. Cell 127: 621–633. [PMC free article: PMC2859215] [PubMed: 17081982]
    60.
    Rauthan M. et al. (2017) MicroRNA regulation of nAChR expression and nicotine-dependent behavior in C. elegans. Cell Reports 21: 1434–1441. [PMC free article: PMC5724378] [PubMed: 29117550]
    61.
    Tissenbaum H.A. (2015) Using C. elegans for aging research. Invertebrate Reproduction & Development 59: 59–63. [PMC free article: PMC4464094] [PubMed: 26136622]
    62.
    Adams M.D. et al. (2000) The genome sequence of Drosophila melanogaster. Science 287: 2185–2195. [PubMed: 10731132]
    63.
    Reiter L.T., Potocki L., Chien S., Gribskov M. and Bier E. (2001) A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Research 11: 1114–1125. [PMC free article: PMC311089] [PubMed: 11381037]
    64.
    Miklos G.L.G. and Maleszka R. (2000) Deus ex genomix. Nature Neuroscience 3: 424–425. [PubMed: 10769377]
    65.
    Neuman S., Kovalio M., Yaffe D. and Nudel U. (2005) The Drosophila homologue of the dystrophin gene – Introns containing promoters are the major contributors to the large size of the gene. FEBS Letters 579: 5365–5371. [PubMed: 16198353]
    66.
    Pozzoli U. et al. (2003) Comparative analysis of vertebrate dystrophin loci indicate intron gigantism as a common feature. Genome Research 13: 764–772. [PMC free article: PMC430921] [PubMed: 12727896]
    67.
    Lander E.S. et al. (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921. [PubMed: 11237011]
    68.
    The Arabidopsis Genome I (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408: 796–815. [PubMed: 11130711]
    69.
    Yu J. et al. (2002) A draft sequence of the rice genome (Oryza sativa L. ssp. indica). Science 296: 79–92. [PubMed: 11935017]
    70.
    Goff S.A. et al. (2002) A draft sequence of the rice genome (Oryza sativa L. ssp. japonica). Science 296: 92–100. [PubMed: 11935018]
    71.
    Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921. [PubMed: 11237011]
    72.
    Venter J.C. et al. (2001) The sequence of the human genome. Science 291: 1304–1351. [PubMed: 11181995]
    73.
    Internation Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431: 931–945. [PubMed: 15496913]
    74.
    Waterston R.H. et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562. [PubMed: 12466850]
    75.
    Gibbs R.A. et al. (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428: 493–521. [PubMed: 15057822]
    76.
    Lindblad-Toh K. et al. (2005) Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438: 803–819. [PubMed: 16341006]
    77.
    Elsik C.G., Tellam R.L. and Worley K.C. (2009) The genome sequence of taurine cattle: A window to ruminant biology and evolution. Science 324: 522–528. [PMC free article: PMC2943200] [PubMed: 19390049]
    78.
    Chimpanzee Sequencing and Analysis Consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437: 69–87. [PubMed: 16136131]
    79.
    Hillier L.W. et al. (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432: 695–716. [PubMed: 15592404]
    80.
    Aparicio S. et al. (2002) Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science 297: 1301–1310. [PubMed: 12142439]
    81.
    Dehal P. et al. (2002) The draft genome of Ciona intestinalis: Insights into chordate and vertebrate origins. Science 298: 2157–2167. [PubMed: 12481130]
    82.
    Brudno M. et al. (2004) Automated whole-genome multiple alignment of rat, mouse, and human. Genome Research 14: 685–692. [PMC free article: PMC383314] [PubMed: 15060011]
    83.
    Demuth J.P., Bie T.D., Stajich J.E., Cristianini N. and Hahn M.W. (2006) The evolution of mammalian gene families. PLOS ONE 1: e85. [PMC free article: PMC1762380] [PubMed: 17183716]
    84.
    Lutfalla G. et al. (2003) Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish. BMC Genomics 4: 29. [PMC free article: PMC179897] [PubMed: 12869211]
    85.
    Niimura Y. and Nei M. (2007) Extensive gains and losses of olfactory receptor genes in mammalian evolution. PLOS ONE 2: e708. [PMC free article: PMC1933591] [PubMed: 17684554]
    86.
    Hahn M.W. and Wray G.A. (2002) The g-value paradox. Evolution & Development 4: 73–75. [PubMed: 12004964]
    87.
    Bird A.P. et al. (1995) Transcriptional noise and the evolution of gene number. Philosophical Transactions of the Royal Society B: Biological Sciences 349: 249–253. [PubMed: 8577835]
    88.
    Hodgkin J. (2001) What does a worm want with 20,000 genes? Genome Biology 2: comment2008.1. [PMC free article: PMC138976] [PubMed: 11737938]
    89.
    Stein L.D. et al. (2003) The genome sequence of Caenorhabditis briggsae: A platform for comparative genomics. PLOS Biology 1: e45. [PMC free article: PMC261899] [PubMed: 14624247]
    90.
    Hillier L.W. et al. (2005) Genomics in C. elegans: So many genes, such a little worm. Genome Research 15: 1651–1660. [PubMed: 16339362]
    91.
    Srivastava M. et al. (2010) The Amphimedon queenslandica genome and the evolution of animal complexity. Nature 466: 720–726. [PMC free article: PMC3130542] [PubMed: 20686567]
    92.
    Chen X.-G. et al. (2015) Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution. Proceedings of the National Academy of Sciences USA 112: E5907–15. [PMC free article: PMC4640774] [PubMed: 26483478]
    93.
    Colbourne J.K. et al. (2011) The ecoresponsive genome of Daphnia pulex. Science 331: 555–561. [PMC free article: PMC3529199] [PubMed: 21292972]
    94.
    Bianconi E. et al. (2013) An estimation of the number of cells in the human body. Annals of Human Biology 40: 463–471. [PubMed: 23829164]
    95.
    Azevedo F.A.C. et al. (2009) Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. Journal of Comparative Neurology 513: 532–541. [PubMed: 19226510]
    96.
    Goodstadt L. and Ponting C.P. (2006) Phylogenetic reconstruction of orthology, paralogy, and conserved synteny for dog and human. PLOS Computational Biology 2: e133. [PMC free article: PMC1584324] [PubMed: 17009864]
    97.
    Clamp M. et al. (2007) Distinguishing protein-coding and noncoding genes in the human genome. Proceedings of the National Academy of Sciences USA 104: 19428–19433. [PMC free article: PMC2148306] [PubMed: 18040051]
    98.
    Church D.M. et al. (2009) Lineage-specific biology revealed by a finished genome assembly of the mouse. PLOS Biology 7: e1000112. [PMC free article: PMC2680341] [PubMed: 19468303]
    99.
    Zimin A.V. et al. (2009) A whole-genome assembly of the domestic cow, Bos taurus. Genome Biology 10: R42. [PMC free article: PMC2688933] [PubMed: 19393038]
    100.
    Pertea M. and Salzberg S.L. (2010) Between a chicken and a grape: Estimating the number of human genes. Genome Biology 11: 206. [PMC free article: PMC2898077] [PubMed: 20441615]
    101.
    Montague M.J. et al. (2014) Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication. Proceedings of the National Academy of Sciences USA 111: 17230–17235. [PMC free article: PMC4260561] [PubMed: 25385592]
    102.
    Willyard C. (2018) New human gene tally reignites debate. Nature 558: 354–355. [PubMed: 29921859]
    103.
    Taft R.J., Pheasant M. and Mattick J.S. (2007) The relationship between non-protein-coding DNA and eukaryotic complexity. BioEssays 29: 288–299. [PubMed: 17295292]
    104.
    Liu G., Mattick J.S. and Taft R.J. (2013) A meta-analysis of the genomic and transcriptomic composition of complex life. Cell Cycle 12: 2061–2072. [PMC free article: PMC3737309] [PubMed: 23759593]
    105.
    Rogers J.C. (1988) RNA complementary to α-amylase mRNA in barley. Plant Molecular Biology 11: 125–138. [PubMed: 24272255]
    106.
    Vinogradov A.E. and Anatskaya O.V. (2007) Organismal complexity, cell differentiation and gene expression: Human over mouse. Nucleic Acids Research 35: 6350–6356. [PMC free article: PMC2095826] [PubMed: 17881362]
    107.
    Bell G. and Mooers A.O. (2008) Size and complexity among multicellular organisms. Biological Journal of the Linnean Society 60: 345–363.
    108.
    Schad E., Tompa P. and Hegyi H. (2011) The relationship between proteome size, structural disorder and organism complexity. Genome Biology 12: R120. [PMC free article: PMC3334615] [PubMed: 22182830]
    109.
    Schmucker D. et al. (2000) Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Cell 101: 671–684. [PubMed: 10892653]
    110.
    Hattori D. et al. (2007) Dscam diversity is essential for neuronal wiring and self-recognition. Nature 449: 223–227. [PMC free article: PMC2691715] [PubMed: 17851526]
    111.
    Deveson I.W. et al. (2018) Universal alternative splicing of noncoding exons. Cell Systems 6: 245–255. [PubMed: 29396323]
    112.
    Tress M.L., Abascal F. and Valencia A. (2017) Alternative splicing may not be the key to proteome complexity. Trends in Biochemical Sciences 42: 98–110. [PMC free article: PMC6526280] [PubMed: 27712956]
    113.
    Levine M. and Tjian R. (2003) Transcription regulation and animal diversity. Nature 424: 147–151. [PubMed: 12853946]
    114.
    Solé R.V., Fernández P. and Kauffman S.A. (2003) Adaptive walks in a gene network model of morphogenesis: Insights into the Cambrian explosion. International Journal of Developmental Biology 47: 685–693. [PubMed: 14756344]
    115.
    Krebs A.R. (2021) Studying transcription factor function in the genome at molecular resolution. Trends in Genetics 37: 798–806. [PubMed: 33892959]
    116.
    Clark A.G. et al. (2007) Evolution of genes and genomes on the Drosophila phylogeny. Nature 450: 203–218. [PubMed: 17994087]
    117.
    Kim B.Y. et al. (2021) Highly contiguous assemblies of 101 drosophilid genomes. eLife 10: e66405. [PMC free article: PMC8337076] [PubMed: 34279216]
    118.
    Bejerano G. et al. (2004) Ultraconserved elements in the human genome. Science 304: 1321–1325. [PubMed: 15131266]
    119.
    Stephen S., Pheasant M., Makunin I.V. and Mattick J.S. (2008) Large-scale appearance of ultraconserved elements in tetrapod genomes and slowdown of the molecular clock. Molecular Biology and Evolution 25: 402–408. [PubMed: 18056681]
    120.
    Katzman S. et al. (2007) Human genome ultraconserved elements are ultraselected. Science 317: 915. [PubMed: 17702936]
    121.
    Bejerano G. et al. (2006) A distal enhancer and an ultraconserved exon are derived from a novel retroposon. Nature 441: 87–90. [PubMed: 16625209]
    122.
    Sandelin A. et al. (2004) Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes. BMC Genomics 5: 99. [PMC free article: PMC544600] [PubMed: 15613238]
    123.
    Poulin F. et al. (2005) In vivo characterization of a vertebrate ultraconserved enhancer. Genomics 85: 774–781. [PubMed: 15885503]
    124.
    Pennacchio L.A. et al. (2006) In vivo enhancer analysis of human conserved non-coding sequences. Nature 444: 499–502. [PubMed: 17086198]
    125.
    Feng J. et al. (2006) The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes & Development 20: 1470–1484. [PMC free article: PMC1475760] [PubMed: 16705037]
    126.
    Visel A. et al. (2008) Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Nature Genetics 40: 158–160. [PMC free article: PMC2647775] [PubMed: 18176564]
    127.
    Calin G.A. et al. (2007) Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 12: 215–229. [PubMed: 17785203]
    128.
    Ferdin J. et al. (2013) HINCUTs in cancer: Hypoxia-induced noncoding ultraconserved transcripts. Cell Death & Differentiation 20: 1675–1687. [PMC free article: PMC3824588] [PubMed: 24037088]
    129.
    Liz J. et al. (2014) Regulation of pri-miRNA processing by a long noncoding RNA transcribed from an ultraconserved region. Molecular Cell 55: 138–147. [PubMed: 24910097]
    130.
    Fiorenzano A. et al. (2018) An ultraconserved element containing lncRNA preserves transcriptional dynamics and maintains ESC self-renewal. Stem Cell Reports 10: 1102–1114. [PMC free article: PMC5918197] [PubMed: 29456181]
    131.
    Zhang C., Peng Y., Wang Y., Xu H. and Zhou X. (2020) Transcribed ultraconserved noncoding RNA uc.153 is a new player in neuropathic pain. Pain 161: 1744–1754. [PubMed: 32701835]
    132.
    Derti A., Roth F.P., Church G.M. and Wu C.T. (2006) Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants. Nature Genetics 38: 1216–1220. [PubMed: 16998490]
    133.
    Wang X. and Goldstein D.B. (2020) Enhancer domains predict gene pathogenicity and inform gene discovery in complex disease. American Journal of Human Genetics 106: 215–233. [PMC free article: PMC7010980] [PubMed: 32032514]
    134.
    Ahituv N. et al. (2007) Deletion of ultraconserved elements yields viable mice. PLOS Biology 5: e234. [PMC free article: PMC1964772] [PubMed: 17803355]
    135.
    Dickel D.E. et al. (2018) Ultraconserved enhancers are required for normal development. Cell 172: 491–499. [PMC free article: PMC5786478] [PubMed: 29358049]
    136.
    Snetkova V. et al. (2021) Ultraconserved enhancer function does not require perfect sequence conservation. Nature Genetics 53: 521–528. [PMC free article: PMC8038972] [PubMed: 33782603]
    137.
    Pittman M. and Pollard K.S. (2021) Ultraconservation of enhancers is not ultranecessary. Nature Genetics 53: 429–430. [PubMed: 33782604]
    138.
    Pollard K.S. et al. (2006) An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443: 167–172. [PubMed: 16915236]
    139.
    Prabhakar S., Noonan J.P., Paabo S. and Rubin E.M. (2006) Accelerated evolution of conserved noncoding sequences in humans. Science 314: 786. [PubMed: 17082449]
    140.
    Rakic P. (2009) Evolution of the neocortex: A perspective from developmental biology. Nature Reviews Neuroscience 10: 724–735. [PMC free article: PMC2913577] [PubMed: 19763105]
    141.
    Molnár Z. and Pollen A. (2014) How unique is the human neocortex? Development 141: 11–16. [PubMed: 24346696]
    142.
    Prabhakar S. et al. (2008) Human-specific gain of function in a developmental enhancer. Science 321: 1346–1350. [PMC free article: PMC2658639] [PubMed: 18772437]
    143.
    Doan R.N. et al. (2016) Mutations in human accelerated regions disrupt cognition and social behavior. Cell 167: 341–354. [PMC free article: PMC5063026] [PubMed: 27667684]
    144.
    Suzuki S., Miyabe E. and Inagaki S. (2018) Novel brain-expressed noncoding RNA, HSTR1, identified at a human-specific variable number tandem repeat locus with a human accelerated region. Biochemical and Biophysical Research Communications 503: 1478–1483. [PubMed: 30029879]
    145.
    Song J.H.T., Lowe C.B. and Kingsley D.M. (2018) Characterization of a human-specific tandem repeat associated with Bipolar Disorder and Schizophrenia. American Journal of Human Genetics 103: 421–430. [PMC free article: PMC6128321] [PubMed: 30100087]
    146.
    Lipovich L., Vanisri R.R., Kong S.L., Lin C.Y. and Liu E.T. (2006) Primate-specific endogenous cis-antisense transcription in the human 5q31 protocadherin gene cluster. Journal of Molecular Evolution 62: 73–88. [PubMed: 16341467]
    147.
    Zhang Z., Pang A.W. and Gerstein M. (2007) Comparative analysis of genome tiling array data reveals many novel primate-specific functional RNAs in human. BMC Evolutionary Biology 7: S14. [PMC free article: PMC1796608] [PubMed: 17288572]
    148.
    Derrien T. et al. (2012) The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Research 22: 1775–1789. [PMC free article: PMC3431493] [PubMed: 22955988]
    149.
    Wang J. et al. (2014) Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells. Nature 516: 405–409. [PubMed: 25317556]
    150.
    Durruthy-Durruthy J. et al. (2016) The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming. Nature Genetics 48: 44–52. [PMC free article: PMC4827613] [PubMed: 26595768]
    151.
    Field A.R. et al. (2019) Structurally conserved primate lncRNAs are transiently expressed during human cortical differentiation and influence cell-type-specific genes. Stem Cell Reports 12: 245–257. [PMC free article: PMC6372947] [PubMed: 30639214]
    152.
    Hennessy E.J. et al. (2019) The long noncoding RNA CHROME regulates cholesterol homeostasis in primates. Nature Metabolism 1: 98–110. [PMC free article: PMC6691505] [PubMed: 31410392]
    153.
    Casanova M. et al. (2019) A primate-specific retroviral enhancer wires the XACT lncRNA into the core pluripotency network in humans. Nature Communications 10: 5652. [PMC free article: PMC6906429] [PubMed: 31827084]
    154.
    Issler O. et al. (2020) Sex-specific role for the long non-coding RNA LINC00473 in depression. Neuron 106: 912–926. [PMC free article: PMC7305959] [PubMed: 32304628]
    155.
    Wilson K.D. et al. (2020) Endogenous retrovirus-derived lncRNA BANCR promotes cardiomyocyte migration in humans and non-human primates. Developmental Cell 54: 694–709. [PMC free article: PMC7529962] [PubMed: 32763147]
    156.
    Liu S. et al. (2020) Identifying common genome-wide risk genes for major psychiatric traits. Human Genetics 139: 185–198. [PubMed: 31813014]
    157.
    Torrents D., Suyama M., Zdobnov E. and Bork P. (2003) A genome-wide survey of human pseudogenes. Genome Research 13: 2559–2567. [PMC free article: PMC403797] [PubMed: 14656963]
    158.
    Vanin E.F. (1985) Processed pseudogenes: Characteristics and evolution. Annual Review of Genetics 19: 253–272. [PubMed: 3909943]
    159.
    Harrison P.M. et al. (2002) Molecular fossils in the human genome: Identification and analysis of the pseudogenes in chromosomes 21 and 22. Genome Research 12: 272–280. [PMC free article: PMC155275] [PubMed: 11827946]
    160.
    Zhang Z., Harrison P.M., Liu Y. and Gerstein M. (2003) Millions of years of evolution preserved: A comprehensive catalog of the processed pseudogenes in the human genome. Genome Research 13: 2541–2558. [PMC free article: PMC403796] [PubMed: 14656962]
    161.
    Carelli F.N. et al. (2016) The life history of retrocopies illuminates the evolution of new mammalian genes. Genome Research 26: 301–314. [PMC free article: PMC4772013] [PubMed: 26728716]
    162.
    Podlaha O. and Zhang J. (2004) Nonneutral evolution of the transcribed pseudogene Makorin1-p1 in mice. Molecular Biology and Evolution 21: 2202–2209. [PubMed: 15306660]
    163.
    Moleirinho A. et al. (2013) Evolutionary constraints in the β-globin cluster: The signature of purifying selection at the δ-globin (HBD) locus and its role in developmental gene regulation. Genome Biology and Evolution 5: 559–571. [PMC free article: PMC3622298] [PubMed: 23431002]
    164.
    Li W., Yang W. and Wang X.-J. (2013) Pseudogenes: Pseudo or real functional elements? Journal of Genetics and Genomics 40: 171–177. [PubMed: 23618400]
    165.
    Ma Y. et al. (2021) Genome-wide analysis of pseudogenes reveals HBBP1′s human-specific essentiality in erythropoiesis and implication in β-thalassemia. Developmental Cell 56: 478–493. [PubMed: 33476555]
    166.
    Korneev S.A., Park J.H. and O‘Shea M. (1999) Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. Journal of Neuroscience 19: 7711–7720. [PMC free article: PMC6782476] [PubMed: 10479675]
    167.
    Hirotsune S. et al. (2003) An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423: 91–96. [PubMed: 12721631]
    168.
    Yano Y. et al. (2004) A new role for expressed pseudogenes as ncRNA: Regulation of mRNA stability of its homologous coding gene. Journal of Molecular Medicine 82: 414–422. [PubMed: 15148580]
    169.
    Devor E.J. (2006) Primate microRNAs miR-220 and miR-492 lie within processed pseudogenes. Journal of Heredity 97: 186–190. [PubMed: 16489141]
    170.
    Tam O.H. et al. (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453: 534–538. [PMC free article: PMC2981145] [PubMed: 18404147]
    171.
    Hawkins P.G. and Morris K.V. (2010) Transcriptional regulation of Oct4 by a long non-coding RNA antisense to Oct4-pseudogene 5. Transcription 1: 165–175. [PMC free article: PMC2999937] [PubMed: 21151833]
    172.
    Poliseno L. et al. (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465: 1033–1038. [PMC free article: PMC3206313] [PubMed: 20577206]
    173.
    Poliseno L. (2012) Pseudogenes: Newly discovered players in human cancer. Science Signaling 5: 5. [PubMed: 22990117]
    174.
    Johnsson P. et al. (2013) A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nature Structural & Molecular Biology 20: 440–446. [PMC free article: PMC3618526] [PubMed: 23435381]
    175.
    Cheetham S.W., Faulkner G.J. and Dinger M.E. (2020) Overcoming challenges and dogmas to understand the functions of pseudogenes. Nature Reviews Genetics 21: 191–201. [PubMed: 31848477]
    176.
    Huang C.R.L., Burns K.H. and Boeke J.D. (2012) Active transposition in genomes. Annual Review of Genetics 46: 651–675. [PMC free article: PMC3612533] [PubMed: 23145912]
    177.
    Wells J.N. and Feschotte C. (2020) A field guide to eukaryotic transposable elements. Annual Review of Genetics 54: 539–561. [PMC free article: PMC8293684] [PubMed: 32955944]
    178.
    Boeke J.D. and Stoye J.P. (1997) Retrotransposons, Endogenous retroviruses, and the evolution of retroelements, in J.M. Coffin, S.H. Hughes and H.E. Varmus, (eds.) Retroviruses (Cold Spring Harbor Laboratory Press, New York). [PubMed: 21433351]
    179.
    Sela N. et al. (2007) Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu’s unique role in shaping the human transcriptome. Genome Biology 8: R127. [PMC free article: PMC2394776] [PubMed: 17594509]
    180.
    Liu G.E., Alkan C., Jiang L., Zhao S. and Eichler E.E. (2009) Comparative analysis of Alu repeats in primate genomes. Genome Research 19: 876–885. [PMC free article: PMC2675976] [PubMed: 19411604]
    181.
    Fedoroff N.V. (2012) Transposable elements, epigenetics, and genome evolution. Science 338: 758–767. [PubMed: 23145453]
    182.
    Weiner A.M. (2002) SINEs and LINEs: The art of biting the hand that feeds you. Current Opinion in Cell Biology 14: 343–350. [PubMed: 12067657]
    183.
    Beck C.R. et al. (2010) LINE-1 retrotransposition activity in human genomes. Cell 141: 1159–1170. [PMC free article: PMC3013285] [PubMed: 20602998]
    184.
    Burns K.H. and Boeke J.D. (2012) Human transposon tectonics. Cell 149: 740–752. [PMC free article: PMC3370394] [PubMed: 22579280]
    185.
    Levanon E.Y. et al. (2004) Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nature Biotechnology 22: 1001–1005. [PubMed: 15258596]
    186.
    Kim D.D. et al. (2004) Widespread RNA editing of embedded alu elements in the human transcriptome. Genome Research 14: 1719–1725. [PMC free article: PMC515317] [PubMed: 15342557]
    187.
    Blow M., Futreal P.A., Wooster R. and Stratton M.R. (2004) A survey of RNA editing in human brain. Genome Research 14: 2379–2387. [PMC free article: PMC534661] [PubMed: 15545495]
    188.
    Athanasiadis A., Rich A. and Maas S. (2004) Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLOS Biology 2: e391. [PMC free article: PMC526178] [PubMed: 15534692]
    189.
    Paz-Yaacov N. et al. (2010) Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates. Proceedings of the National Academy of Sciences USA 107: 12174–12179. [PMC free article: PMC2901480] [PubMed: 20566853]
    190.
    Bazak L. et al. (2014) A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes. Genome Research 24: 365–376. [PMC free article: PMC3941102] [PubMed: 24347612]
    191.
    Zhang X.-O., Gingeras T.R. and Weng Z. (2019) Genome-wide analysis of polymerase III–transcribed Alu elements suggests cell-type–specific enhancer function. Genome Research 29: 1402–1414. [PMC free article: PMC6724667] [PubMed: 31413151]
    192.
    Tomilin N.V. (2008) Regulation of mammalian gene expression by retroelements and non-coding tandem repeats. BioEssays 30: 338–348. [PubMed: 18348251]
    193.
    Boissinot S. and Sookdeo A. (2016) The evolution of LINE-1 in vertebrates. Genome Biology and Evolution 8: 3485–3507. [PMC free article: PMC5381506] [PubMed: 28175298]
    194.
    Tsirigos A. and Rigoutsos I. (2009) Alu and B1 repeats have been selectively retained in the upstream and intronic regions of genes of specific functional classes. PLOS Computational Biology 5: e1000610. [PMC free article: PMC2784220] [PubMed: 20019790]
    195.
    Shapiro J.A. and von Sternberg R. (2005) Why repetitive DNA is essential to genome function. Biological Reviews of the Cambridge Philosophical Society 80: 227–250. [PubMed: 15921050]
    196.
    Brunet T.D.P. and Doolittle W.F. (2015) Multilevel selection theory and the evolutionary functions of transposable elements. Genome Biology and Evolution 7: 2445–2457. [PMC free article: PMC4558868] [PubMed: 26253318]
    197.
    Kleckner N. (1981) Transposable elements in prokaryotes. Annual Review of Genetics 15: 341–404. [PubMed: 6279020]
    198.
    Shapiro J.A. (1992) Natural genetic engineering in evolution. Genetica 86: 99–111. [PubMed: 1334920]
    199.
    Witzany G. (2009) Natural Genetic Engineering and Natural Genome Editing, Annals of the New York Academy of Sciences, vol. 1178 (Wiley-Blackwell, New York). [PubMed: 19845624]
    200.
    Roller M. et al. (2021) LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions. Genome Biology 22: 62. [PMC free article: PMC7890895] [PubMed: 33602314]
    201.
    Cosby R.L. et al. (2021) Recurrent evolution of vertebrate transcription factors by transposase capture. Science 371: eabc6405. [PMC free article: PMC8186458] [PubMed: 33602827]
    202.
    Brosius J. (2003) How significant is 98.5% ‘junk’ in mammalian genomes? Bioinformatics 19(Suppl 2): ii35.
    203.
    Brosius J. (2003) The contribution of RNAs and retroposition to evolutionary novelties. Genetica 118: 99–116. [PubMed: 12868601]
    204.
    Jurka J. (2004) Evolutionary impact of human Alu repetitive elements. Current Opinion in Genetics and Development 14: 603–608. [PubMed: 15531153]
    205.
    Brandt J. et al. (2005) Transposable elements as a source of genetic innovation: Expression and evolution of a family of retrotransposon-derived neogenes in mammals. Gene 345: 101–111. [PubMed: 15716091]
    206.
    Volff J.N. (2006) Turning junk into gold: Domestication of transposable elements and the creation of new genes in eukaryotes. BioEssays 28: 913–922. [PubMed: 16937363]
    207.
    Volff J.N. and Brosius J. (2007) Modern genomes with retro-look: Retrotransposed elements, retroposition and the origin of new genes. Gene and Protein Evolution 3: 175–190. [PubMed: 18753792]
    208.
    Feschotte C. and Pritham E.J. (2007) DNA transposons and the evolution of eukaryotic genomes. Annual Review of Genetics 41: 331–368. [PMC free article: PMC2167627] [PubMed: 18076328]
    209.
    Jurka J., Kapitonov V.V., Kohany O. and Jurka M.V. (2007) Repetitive sequences in complex genomes: Structure and evolution. Annual Review of Genomics and Human Genetics 8: 241–259. [PubMed: 17506661]
    210.
    Oliver K.R. and Greene W.K. (2009) Transposable elements: Powerful facilitators of evolution. BioEssays 31: 703–714. [PubMed: 19415638]
    211.
    Zeh D.W., Zeh J.A. and Ishida Y. (2009) Transposable elements and an epigenetic basis for punctuated equilibria. BioEssays 31: 715–726. [PubMed: 19472370]
    212.
    Britten R.J. (2010) Transposable element insertions have strongly affected human evolution. Proceedings of the National Academy of Sciences USA 107: 19945–19948. [PMC free article: PMC2993358] [PubMed: 21041622]
    213.
    Vogel G. (2011) Retrotransposons. Do jumping genes spawn diversity? Science 332: 300–301. [PubMed: 21493838]
    214.
    Johnson R. and Guigo R. (2014) The RIDL hypothesis: Transposable elements as functional domains of long noncoding RNAs. RNA 20: 959–976. [PMC free article: PMC4114693] [PubMed: 24850885]
    215.
    Dubin M.J., Mittelsten Scheid O. and Becker C. (2018) Transposons: A blessing curse. Current Opinion in Plant Biology 42: 23–29. [PubMed: 29453028]
    216.
    Cosby R.L., Chang N.-C. and Feschotte C. (2019) Host-transposon interactions: Conflict, cooperation, and cooption. Genes & Development 33: 1098–1116. [PMC free article: PMC6719617] [PubMed: 31481535]
    217.
    Peaston A.E. et al. (2004) Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Developmental Cell 7: 597–606. [PubMed: 15469847]
    218.
    Feschotte C. (2008) Transposable elements and the evolution of regulatory networks. Nature Reviews Genetics 9: 397–405. [PMC free article: PMC2596197] [PubMed: 18368054]
    219.
    Faulkner G.J. (2011) Retrotransposons: Mobile and mutagenic from conception to death. FEBS Letters 585: 1589–1594. [PubMed: 21477589]
    220.
    Göke J. et al. (2015) Dynamic transcription of distinct classes of endogenous retroviral elements marks specific populations of early human embryonic cells. Cell Stem Cell 16: 135–141. [PubMed: 25658370]
    221.
    Göke J. and Ng H.H. (2016) CTRL+INSERT: Retrotransposons and their contribution to regulation and innovation of the transcriptome. EMBO Reports 17: 1131–1144. [PMC free article: PMC4967949] [PubMed: 27402545]
    222.
    Lowe C.B., Bejerano G. and Haussler D. (2007) Thousands of human mobile element fragments undergo strong purifying selection near developmental genes. Proceedings of the National Academy of Sciences USA 104: 800 5–10. [PMC free article: PMC1876562] [PubMed: 17463089]
    223.
    Simons C., Pheasant M., Makunin I.V. and Mattick J.S. (2006) Transposon-free regions in mammalian genomes. Genome Research 16: 164–172. [PMC free article: PMC1361711] [PubMed: 16365385]
    224.
    Jordan I.K., Rogozin I.B., Glazko G.V. and Koonin E.V. (2003) Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends in Genetics 19: 68–72. [PubMed: 12547512]
    225.
    Faulkner G.J. et al. (2009) The regulated retrotransposon transcriptome of mammalian cells. Nature Genetics 41: 563–571. [PubMed: 19377475]
    226.
    Xu A.G. et al. (2010) Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq. PLOS Computational Biology 6: e1000843. [PMC free article: PMC2895644] [PubMed: 20617162]
    227.
    Skryabin B.V. et al. (1998) The BC200 RNA gene and its neural expression are conserved in Anthropoidea (Primates). Journal of Molecular Evolution 47: 677–685. [PubMed: 9847409]
    228.
    Silva J.C., Shabalina S.A., Harris D.G., Spouge J.L. and Kondrashovi A.S. (2003) Conserved fragments of transposable elements in intergenic regions: Evidence for widespread recruitment of MIR- and L2-derived sequences within the mouse and human genomes. Genetics Research 82: 1–18. [PubMed: 14621267]
    229.
    Xie X., Kamal M. and Lander E.S. (2006) A family of conserved noncoding elements derived from an ancient transposable element. Proceedings of the National Academy of Sciences USA 103: 11659–11664. [PMC free article: PMC1518811] [PubMed: 16864796]
    230.
    Nishihara H., Smit A.F. and Okada N. (2006) Functional noncoding sequences derived from SINEs in the mammalian genome. Genome Research 16: 864–874. [PMC free article: PMC1484453] [PubMed: 16717141]
    231.
    Brosius J. (1999) RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements. Gene 238: 115–134. [PubMed: 10570990]
    232.
    Kuryshev V.Y., Skryabin B.V., Kremerskothen J., Jurka J. and Brosius J. (2001) Birth of a gene: Locus of neuronal BC200 snmRNA in three prosimians and human BC200 pseudogenes as archives of change in the Anthropoidea lineage. Journal of Molecular Biology 309: 1049–1066. [PubMed: 11399078]
    233.
    Britten R. (2006) Transposable elements have contributed to thousands of human proteins. Proceedings of the National Academy of Sciences USA 103: 1798–1803. [PMC free article: PMC1413650] [PubMed: 16443682]
    234.
    Cordaux R., Udit S., Batzer M.A. and Feschotte C. (2006) Birth of a chimeric primate gene by capture of the transposase gene from a mobile element. Proceedings of the National Academy of Sciences USA 103: 8101–8106. [PMC free article: PMC1472436] [PubMed: 16672366]
    235.
    Krull M., Brosius J. and Schmitz J. (2005) Alu-SINE exonization: En route to protein-coding function. Molecular Biology and Evolution 22: 1702–1711. [PubMed: 15901843]
    236.
    Hezroni H. et al. (2015) Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Reports 11: 1110–1122. [PMC free article: PMC4576741] [PubMed: 25959816]
    237.
    Gerdes P., Richardson S.R., Mager D.L. and Faulkner G.J. (2016) Transposable elements in the mammalian embryo: Pioneers surviving through stealth and service. Genome Biology 17: 100. [PMC free article: PMC4862087] [PubMed: 27161170]
    238.
    Yadav V. et al. (2018) RNAi is a critical determinant of centromere evolution in closely related fungi. Proceedings of the National Academy of Sciences USA 115: 3108–3113. [PMC free article: PMC5866544] [PubMed: 29507212]
    239.
    Hartley G. and O‘Neill R.J. (2019) Centromere repeats: Hidden gems of the genome. Genes 10: 223. [PMC free article: PMC6471113] [PubMed: 30884847]
    240.
    van de Lagemaat L.N., Landry J.-R., Mager D.L. and Medstrand P. (2003) Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends in Genetics 19: 530–536. [PubMed: 14550626]
    241.
    Bourque G. et al. (2008) Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Research 18: 1752–1762. [PMC free article: PMC2577865] [PubMed: 18682548]
    242.
    Hermant C. and Torres-Padilla M.-E. (2021) TFs for TEs: The transcription factor repertoire of mammalian transposable elements. Genes & Development 35: 22–39. [PMC free article: PMC7778262] [PubMed: 33397727]
    243.
    Matlik K., Redik K. and Speek M. (2006) L1 antisense promoter drives tissue-specific transcription of human genes. Journal of Biomedicine and Biotechnology 2006: 71753. [PMC free article: PMC1559930] [PubMed: 16877819]
    244.
    Lunyak V.V. et al. (2007) Developmentally regulated activation of a SINE B2 repeat as a domain boundary in organogenesis. Science 317: 248–251. [PubMed: 17626886]
    245.
    Kelley D. and Rinn J. (2012) Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biology 13: R107. [PMC free article: PMC3580499] [PubMed: 23181609]
    246.
    Trizzino M. et al. (2017) Transposable elements are the primary source of novelty in primate gene regulation. Genome Research 27: 1623–1633. [PMC free article: PMC5630026] [PubMed: 28855262]
    247.
    Ferrigno O. et al. (2001) Transposable B2 SINE elements can provide mobile RNA polymerase II promoters. Nature Genetics 28: 77–81. [PubMed: 11326281]
    248.
    Nigumann P., Redik K., Matlik K. and Speek M. (2002) Many human genes are transcribed from the antisense promoter of L1 retrotransposon. Genomics 79: 628–634. [PubMed: 11991712]
    249.
    Speek M. (2001) Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes. Molecular and Cellular Biology 21: 1973–1985. [PMC free article: PMC86790] [PubMed: 11238933]
    250.
    Ludwig A., Rozhdestvensky T.S., Kuryshev V.Y., Schmitz J. and Brosius J. (2005) An unusual primate locus that attracted two independent Alu insertions and facilitates their transcription. Journal of Molecular Biology 350: 200–214. [PubMed: 15922354]
    251.
    Romanish M.T., Lock W.M., de Lagemaat L.N., Dunn C.A. and Mager D.L. (2007) Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution. PLOS Genetics 3: e10. [PMC free article: PMC1781489] [PubMed: 17222062]
    252.
    Whitelaw E. and Martin D.I. (2001) Retrotransposons as epigenetic mediators of phenotypic variation in mammals. Nature Genetics 27: 361–365. [PubMed: 11279513]
    253.
    Schramke V. and Allshire R. (2003) Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science 301: 1069–1074. [PubMed: 12869699]
    254.
    Lippman Z. et al. (2004) Role of transposable elements in heterochromatin and epigenetic control. Nature 430: 471–476. [PubMed: 15269773]
    255.
    Slotkin R.K. and Martienssen R. (2007) Transposable elements and the epigenetic regulation of the genome. Nature Reviews Genetics 8: 272–285. [PubMed: 17363976]
    256.
    Chueh A.C., Northrop E.L., Brettingham-Moore K.H., Choo K.H. and Wong L.H. (2009) LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin. PLOS Genetics 5: e1000354. [PMC free article: PMC2625447] [PubMed: 19180186]
    257.
    Gehring M., Bubb K.L. and Henikoff S. (2009) Extensive demethylation of repetitive elements during seed development underlies gene imprinting. Science 324: 1447–1451. [PMC free article: PMC2886585] [PubMed: 19520961]
    258.
    McCue A.D., Nuthikattu S., Reeder S.H. and Slotkin R.K. (2012) Gene expression and stress response mediated by the epigenetic regulation of a transposable element small RNA. PLOS Genetics 8: e1002474. [PMC free article: PMC3276544] [PubMed: 22346759]
    259.
    Brind’Amour J. et al. (2018) LTR retrotransposons transcribed in oocytes drive species-specific and heritable changes in DNA methylation. Nature Communications 9: 3331. [PMC free article: PMC6102241] [PubMed: 30127397]
    260.
    Bogutz A.B. et al. (2019) Evolution of imprinting via lineage-specific insertion of retroviral promoters. Nature Communications 10: 5674. [PMC free article: PMC6908575] [PubMed: 31831741]
    261.
    Kelley D.R., Hendrickson D.G., Tenen D. and Rinn J.L. (2014) Transposable elements modulate human RNA abundance and splicing via specific RNA-protein interactions. Genome Biology 15: 537. [PMC free article: PMC4272801] [PubMed: 25572935]
    262.
    Landry J.R., Medstrand P. and Mager D.L. (2001) Repetitive elements in the 5′ untranslated region of a human zinc-finger gene modulate transcription and translation efficiency. Genomics 76: 110–116. [PubMed: 11549323]
    263.
    Lubelsky Y. and Ulitsky I. (2018) Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells. Nature 555: 107–111. [PMC free article: PMC6047738] [PubMed: 29466324]
    264.
    Carlevaro-Fita J. et al. (2019) Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs. Genome Research 29: 208–222. [PMC free article: PMC6360812] [PubMed: 30587508]
    265.
    Lewejohann L. et al. (2004) Role of a neuronal small non-messenger RNA: Behavioural alterations in BC1 RNA-deleted mice. Behavioural Brain Research 154: 273–289. [PubMed: 15302134]
    266.
    Volpe T.A. et al. (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297: 1833–1837. [PubMed: 12193640]
    267.
    Ferrari R. et al. (2020) TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation. Molecular Cell 77: 475–487. [PMC free article: PMC7014570] [PubMed: 31759822]
    268.
    Diehl A.G., Ouyang N. and Boyle A.P. (2020) Transposable elements contribute to cell and species-specific chromatin looping and gene regulation in mammalian genomes. Nature Communications 11: 1796. [PMC free article: PMC7156512] [PubMed: 32286261]
    269.
    Choudhary M.N.K. et al. (2020) Co-opted transposons help perpetuate conserved higher-order chromosomal structures. Genome Biology 21: 16. [PMC free article: PMC6979391] [PubMed: 31973766]
    270.
    Brown S.W. (1966) Heterochromatin. Science 151: 417–425. [PubMed: 5322971]
    271.
    Pontis J. et al. (2019) Hominoid-specific transposable elements and KZFPs facilitate human embryonic genome activation and control transcription in naive human ESCs. Cell Stem Cell 24: 724–735. [PMC free article: PMC6509360] [PubMed: 31006620]
    272.
    Wolf G. et al. (2020) KRAB-zinc finger protein gene expansion in response to active retrotransposons in the murine lineage. eLife 9: e56337. [PMC free article: PMC7289599] [PubMed: 32479262]
    273.
    Bulut-Karslioglu A. et al. (2012) A transcription factor–based mechanism for mouse heterochromatin formation. Nature Structural & Molecular Biology 19: 1023–1030. [PubMed: 22983563]
    274.
    Turelli P. et al. (2020) Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons. Science Advances 6: eaba3200. [PMC free article: PMC7455193] [PubMed: 32923624]
    275.
    Babarinde Isaac A. et al. (2021) Transposable element sequence fragments incorporated into coding and noncoding transcripts modulate the transcriptome of human pluripotent stem cells. Nucleic Acids Research 49: 9132–9153. [PMC free article: PMC8450112] [PubMed: 34390351]
    276.
    Lu X. et al. (2014) The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nature Structural & Molecular Biology 21: 423–425. [PubMed: 24681886]
    277.
    Fort A. et al. (2014) Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nature Genetics 46: 558–566. [PubMed: 24777452]
    278.
    Jacques P.É., Jeyakani J. and Bourque G. (2013) The majority of primate-specific regulatory sequences are derived from transposable elements. PLOS Genetics 9: e1003504. [PMC free article: PMC3649963] [PubMed: 23675311]
    279.
    Macfarlan T.S. et al. (2012) Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487: 57–63. [PMC free article: PMC3395470] [PubMed: 22722858]
    280.
    Modzelewski A.J. et al. (2021) A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development. Cell 184: 5541–5558. [PMC free article: PMC8787082] [PubMed: 34644528]
    281.
    Singh K., Carey M., Saragosti S. and Botchan M. (1985) Expression of enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats in simian virus 40-transformed mouse cells. Nature 314: 553–556. [PubMed: 2581137]
    282.
    Fornace Jr. A.J., and Mitchell J.B. (1986) Induction of B2 RNA polymerase III transcription by heat shock: Enrichment for heat shock induced sequences in rodent cells by hybridization subtraction. Nucleic Acids Research 14: 5793–5811. [PMC free article: PMC311592] [PubMed: 2426659]
    283.
    Jang K.L. and Latchman D.S. (1989) HSV infection induces increased transcription of Alu repeated sequences by RNA polymerase III. FEBS Letters 258: 255–258. [PubMed: 2557237]
    284.
    Jang K.L. and Latchman D.S. (1992) The herpes simplex virus immediate-early protein ICP27 stimulates the transcription of cellular Alu repeated sequences by increasing the activity of transcription factor TFIIIC. Biochemical Journal 284: 667–673. [PMC free article: PMC1132590] [PubMed: 1320373]
    285.
    Panning B. and Smiley J.R. (1993) Activation of RNA polymerase III transcription of human Alu repetitive elements by adenovirus type 5: Requirement for the E1b 58-kilodalton protein and the products of E4 open reading frames 3 and 6. Molecular and Cellular Biology 13: 3231–3244. [PMC free article: PMC359768] [PubMed: 7684492]
    286.
    Russanova V.R., Driscoll C.T. and Howard B.H. (1995) Adenovirus type 2 preferentially stimulates polymerase III transcription of Alu elements by relieving repression: A potential role for chromatin. Molecular and Cellular Biology 15: 4282–4290. [PMC free article: PMC230667] [PubMed: 7623822]
    287.
    Liu W.M., Chu W.M., Choudary P.V. and Schmid C.W. (1995) Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts. Nucleic Acids Research 23: 1758–1765. [PMC free article: PMC306933] [PubMed: 7784180]
    288.
    Li T.-H., Spearow J., Rubin C.M. and Schmid C.W. (1999) Physiological stresses increase mouse short interspersed element (SINE) RNA expression in vivo. Gene 239: 367–372. [PubMed: 10548739]
    289.
    Kimura R.H., Choudary P.V., Stone K.K. and Schmid C.W. (2001) Stress induction of Bm1 RNA in silkworm larvae: SINEs, an unusual class of stress genes. Cell Stress & Chaperones 6: 263–272. [PMC free article: PMC434408] [PubMed: 11599568]
    290.
    Rudin C.M. and Thompson C.B. (2001) Transcriptional activation of short interspersed elements by DNA-damaging agents. Genes, Chromosomes and Cancer 30: 64–71. [PubMed: 11107177]
    291.
    Kigami D., Minami N., Takayama H. and Imai H. (2003) MuERV-L is one of the earliest transcribed genes in mouse one-cell embryos. Biology of Reproduction 68: 651–654. [PubMed: 12533431]
    292.
    Marasca F. et al. (2022) LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion. Nature Genetics 50: 180–193. [PubMed: 35039641]
    293.
    Moore R.S. et al. (2021) The role of the Cer1 transposon in horizontal transfer of transgenerational memory. Cell 184: 4697–4712. [PMC free article: PMC8812995] [PubMed: 34363756]
    294.
    Wong W.Y. et al. (2019) Expansion of a single transposable element family is associated with genome-size increase and radiation in the genus Hydra. Proceedings of the National Academy of Sciences USA 116: 22915–22917. [PMC free article: PMC6859323] [PubMed: 31659034]
    295.
    Etchegaray E., Naville M., Volff J.-N. and Haftek-Terreau Z. (2021) Transposable element-derived sequences in vertebrate development. Mobile DNA 12: 1. [PMC free article: PMC7786948] [PubMed: 33407840]
    296.
    Wang K. et al. (2021) African lungfish genome sheds light on the vertebrate water-to-land transition. Cell 184: 1362–1376. [PubMed: 33545087]
    297.
    Xia B. et al. (2021) The genetic basis of tail-loss evolution in humans and apes. bioRxiv: 2021.09.14.460388.
    298.
    Patoori S., Barnada S. and Trizzino M. (2021) Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors. bioRxiv epub: 2021.11.24.469877. [PMC free article: PMC9641669] [PubMed: 36052683]
    299.
    Gray M.M., Sutter N.B., Ostrander E.A. and Wayne R.K. (2010) The IGF1 small dog haplotype is derived from Middle Eastern grey wolves. BMC Biology 8: 16. [PMC free article: PMC2837629] [PubMed: 20181231]
    300.
    Wang W. and Kirkness E.F. (2005) Short interspersed elements (SINEs) are a major source of canine genomic diversity. Genome Research 15: 1798–1808. [PMC free article: PMC1356118] [PubMed: 16339378]
    301.
    Halo J.V. et al. (2021) Long-read assembly of a Great Dane genome highlights the contribution of GC-rich sequence and mobile elements to canine genomes. Proceedings of the National Academy of Sciences USA 118: e2016274118. [PMC free article: PMC7980453] [PubMed: 33836575]
    302.
    David V.A. et al. (2014) Endogenous retrovirus insertion in the KIT oncogene determines white and white spotting in domestic cats. G3 (Genes, Genomes, Genetics) 4: 1881–1891. [PMC free article: PMC4199695] [PubMed: 25085922]
    303.
    Kratochwil C.F. et al. (2022) An intronic transposon insertion associates with a trans-species color polymorphism in Midas cichlid fishes. Nature Communications 13: 296. [PMC free article: PMC8758764] [PubMed: 35027541]
    304.
    Hiom K., Melek M. and Gellert M. (1998) DNA transposition by the RAG1 and RAG2 proteins: A possible source of oncogenic translocations. Cell 94: 463–470. [PubMed: 9727489]
    305.
    Kapitonov V.V. and Jurka J. (2005) RAG1 core and V(D)J recombination signal sequences were derived from transib transposons. PLOS Biology 3: e181. [PMC free article: PMC1131882] [PubMed: 15898832]
    306.
    Sznarkowska A., Mikac S. and Pilch M. (2020) MHC class I regulation: The origin perspective. Cancers 12: 1155. [PMC free article: PMC7281430] [PubMed: 32375397]
    307.
    Chuong E.B., Elde N.C. and Feschotte C. (2016) Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 351: 1083–1087. [PMC free article: PMC4887275] [PubMed: 26941318]
    308.
    Haldane J.B.S. (1924) A mathematical theory of natural and artificial selection. Part I. (The Causes of Evolution. London: Longmans, Green). Transactions of the Cambridge Philosophical Society 23: 19–41.
    309.
    Sarkar S. (1992) The founders of theoretical evolutionary genetics, in S. Sarkar (ed.) The Founders of Evolutionary Genetics (Springer, New York).
    310.
    v’ant Hof A.E. et al. (2016) The industrial melanism mutation in British peppered moths is a transposable element. Nature 534: 102–105. [PubMed: 27251284]
    311.
    Nadeau N.J. et al. (2016) The gene cortex controls mimicry and crypsis in butterflies and moths. Nature 534: 106–110. [PMC free article: PMC5094491] [PubMed: 27251285]
    312.
    v’ant Hof A.E., Edmonds N., Dalikova M., Marec F. and Saccheri I.J. (2011) Industrial melanism in British peppered moths has a singular and recent mutational origin. Science 332: 958–960. [PubMed: 21493823]
    313.
    Xiao H., Jiang N., Schaffner E., Stockinger E.J. and van der Knaap E. (2008) A retrotransposon-mediated gene duplication underlies morphological variation of tomato fruit. Science 319: 1527–1530. [PubMed: 18339939]
    314.
    Studer A., Zhao Q., Ross-Ibarra J. and Doebley J. (2011) Identification of a functional transposon insertion in the maize domestication gene tb1. Nature Genetics 43: 1160–1163. [PMC free article: PMC3686474] [PubMed: 21946354]
    315.
    Huang C. et al. (2018) ZmCCT9 enhances maize adaptation to higher latitudes. Proceedings of the National Academy of Sciences USA 115: E334–41. [PMC free article: PMC5777075] [PubMed: 29279404]
    316.
    Kobayashi S., Goto-Yamamoto N. and Hirochika H. (2004) Retrotransposon-induced mutations in grape skin color. Science 304: 982. [PubMed: 15143274]
    317.
    Zhang L. et al. (2019) A high-quality apple genome assembly reveals the association of a retrotransposon and red fruit colour. Nature Communications 10: 1494. [PMC free article: PMC6445120] [PubMed: 30940818]
    318.
    Butelli E. et al. (2012) Retrotransposons control fruit-specific, cold-dependent accumulation of anthocyanins in blood oranges. Plant Cell 24: 1242–1255. [PMC free article: PMC3336134] [PubMed: 22427337]
    319.
    Baduel P. et al. (2021) Genetic and environmental modulation of transposition shapes the evolutionary potential of Arabidopsis thaliana. Genome Biology 22: 138. [PMC free article: PMC8101250] [PubMed: 33957946]
    320.
    Vitte C., Estep M.C., Leebens-Mack J. and Bennetzen J.L. (2013) Young, intact and nested retrotransposons are abundant in the onion and asparagus genomes. Annals of Botany 112: 881–889. [PMC free article: PMC3747808] [PubMed: 23887091]
    321.
    Wang Q. and Dooner H.K. (2006) Remarkable variation in maize genome structure inferred from haplotype diversity at the bz locus. Proceedings of the National Academy of Sciences USA 103: 17644–17649. [PMC free article: PMC1693800] [PubMed: 17101975]
    322.
    Jiao Y. et al. (2017) Improved maize reference genome with single-molecule technologies. Nature 546: 524–527. [PMC free article: PMC7052699] [PubMed: 28605751]
    323.
    Stitzer M.C., Anderson S.N., Springer N.M. and Ross-Ibarra J. (2021) The genomic ecosystem of transposable elements in maize. PLOS Genetics 17: e1009768. [PMC free article: PMC8547701] [PubMed: 34648488]
    324.
    Liedtke H.C., Gower D.J., Wilkinson M. and Gomez-Mestre I. (2018) Macroevolutionary shift in the size of amphibian genomes and the role of life history and climate. Nature Ecology & Evolution 2: 1792–1799. [PubMed: 30250158]
    325.
    Lertzman-Lepofsky G., Mooers A.Ø. and Greenberg D.A. (2019) Ecological constraints associated with genome size across salamander lineages. Proceedings of the Royal Society B: Biological Sciences 286: 20191780. [PMC free article: PMC6784731] [PubMed: 31530144]
    326.
    Canapa A. et al. (2020) Shedding light upon the complex net of genome size, genome composition and environment in chordates. European Zoological Journal 87: 192–202.
    327.
    Calarco J.P. et al. (2012) Reprogramming of DNA methylation in pollen guides epigenetic inheritance via small RNA. Cell 151: 194–205. [PMC free article: PMC3697483] [PubMed: 23000270]
    328.
    Chandler V.L. and Walbot V. (1986) DNA modification of a maize transposable element correlates with loss of activity. Proceedings of the National Academy of Sciences USA 83: 1767–1771. [PMC free article: PMC323165] [PubMed: 3006070]
    329.
    Chomet P.S., Wessler S. and Dellaporta S.L. (1987) Inactivation of the maize transposable element Activator (Ac) is associated with its DNA modification. EMBO Journal 6: 295–302. [PMC free article: PMC553394] [PubMed: 3034583]
    330.
    Fedoroff N.V. (1989) About maize transposable elements and development. Cell 56: 181–191. [PubMed: 2536297]
    331.
    Bertozzi T.M., Takahashi N., Hanin G., Kazachenka A. and Ferguson-Smith A.C. (2021) A spontaneous genetically induced epiallele at a retrotransposon shapes host genome function. eLife 10: e65233. [PMC free article: PMC8084528] [PubMed: 33755012]
    332.
    Mikkelsen T.S. et al. (2007) Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. Nature 447: 167–177. [PubMed: 17495919]
    333.
    Gemmell N.J. et al. (2020) The tuatara genome reveals ancient features of amniote evolution. Nature 584: 403–409. [PMC free article: PMC7116210] [PubMed: 32760000]
    334.
    Meyer A. et al. (2021) Giant lungfish genome elucidates the conquest of land by vertebrates. Nature 590: 284–289. [PMC free article: PMC7875771] [PubMed: 33461212]
    335.
    Jeffreys A.J. (1987) Highly variable minisatellites and DNA fingerprints. Biochemical Society Transactions 15: 309–317. [PubMed: 2887471]
    336.
    Willems T. et al. (2014) The landscape of human STR variation. Genome Research 24: 1894–1904. [PMC free article: PMC4216929] [PubMed: 25135957]
    337.
    Kashi Y. and King D.G. (2006) Simple sequence repeats as advantageous mutators in evolution. Trends in Genetics 22: 253–259. [PubMed: 16567018]
    338.
    Vinces M.D., Legendre M., Caldara M., Hagihara M. and Verstrepen K.J. (2009) Unstable tandem repeats in promoters confer transcriptional evolvability. Science 324: 1213–1216. [PMC free article: PMC3132887] [PubMed: 19478187]
    339.
    Gymrek M. et al. (2016) Abundant contribution of short tandem repeats to gene expression variation in humans. Nature Genetics 48: 22–29. [PMC free article: PMC4909355] [PubMed: 26642241]
    340.
    Bagshaw A.T.M. (2017) Functional mechanisms of microsatellite DNA in eukaryotic genomes. Genome Biology and Evolution 9: 2428–2443. [PMC free article: PMC5622345] [PubMed: 28957459]
    341.
    Quilez J. et al. (2016) Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans. Nucleic Acids Research 44: 3750–3762. [PMC free article: PMC4857002] [PubMed: 27060133]
    342.
    Kim Y.B. et al. (2014) Divergence of Drosophila melanogaster repeatomes in response to a sharp microclimate contrast in Evolution Canyon, Israel. Proceedings of the National Academy of Sciences USA 111: 10630–10635. [PMC free article: PMC4115526] [PubMed: 25006263]
    343.
    Budworth H. and McMurray C.T. (2013) A brief history of triplet repeat diseases. Methods in Molecular Biology 1010: 3–17. [PMC free article: PMC3913379] [PubMed: 23754215]
    344.
    Trost B. et al. (2020) Genome-wide detection of tandem DNA repeats that are expanded in autism. Nature 586: 80–86. [PMC free article: PMC9348607] [PubMed: 32717741]
    345.
    Tempel S. (2012) Using and understanding RepeatMasker, in W. J. Miller and P. Capy (eds.) Mobile Genetic Elements: Protocols and Genomic Applications (Humana Press, New York).
    346.
    347.
    Braslavsky I., Hebert B., Kartalov E. and Quake S.R. (2003) Sequence information can be obtained from single DNA molecules. Proceedings of the National Academy of Sciences USA 100: 3960–3964. [PMC free article: PMC153030] [PubMed: 12651960]
    348.
    Deamer D., Akeson M. and Branton D. (2016) Three decades of nanopore sequencing. Nature Biotechnology 34: 518–524. [PMC free article: PMC6733523] [PubMed: 27153285]
    349.
    Soylev A., Le T.M., Amini H., Alkan C. and Hormozdiari F. (2019) Discovery of tandem and interspersed segmental duplications using high-throughput sequencing. Bioinformatics 35: 3923–3930. [PMC free article: PMC6792081] [PubMed: 30937433]
    350.
    Disdero E. and Filée J. (2017) LoRTE: Detecting transposon-induced genomic variants using low coverage PacBio long read sequences. Mobile DNA 8: 5. [PMC free article: PMC5385071] [PubMed: 28405230]
    351.
    Giani A.M., Gallo G.R., Gianfranceschi L. and Formenti G. (2019) Long walk to genomics: History and current approaches to genome sequencing and assembly. Computational and Structural Biotechnology Journal 18: 9–19. [PMC free article: PMC6926122] [PubMed: 31890139]
    352.
    Zhou W. et al. (2020) Identification and characterization of occult human-specific LINE-1 insertions using long-read sequencing technology. Nucleic Acids Research 48: 1146–1163. [PMC free article: PMC7026601] [PubMed: 31853540]
    353.
    Jain M. et al. (2018) Nanopore sequencing and assembly of a human genome with ultra-long reads. Nature Biotechnology 36: 338–345. [PMC free article: PMC5889714] [PubMed: 29431738]
    354.
    Miga K.H. et al. (2020) Telomere-to-telomere assembly of a complete human X chromosome. Nature 585: 79–84. [PMC free article: PMC7484160] [PubMed: 32663838]
    355.
    Nurk S. et al. (2020) HiCanu: Accurate assembly of segmental duplications, satellites, and allelic variants from high-fidelity long reads. Genome Research 30: 1291–1305. [PMC free article: PMC7545148] [PubMed: 32801147]
    356.
    Bentley D.R. et al. (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456: 53–59. [PMC free article: PMC2581791] [PubMed: 18987734]
    357.
    Heather J.M. and Chain B. (2016) The sequence of sequencers: The history of sequencing DNA. Genomics 107: 1–8. [PMC free article: PMC4727787] [PubMed: 26554401]
    358.
    Shulgina Y. and Eddy S.R. (2021) A computational screen for alternative genetic codes in over 250,000 genomes. eLife 10: e71402. [PMC free article: PMC8629427] [PubMed: 34751130]
    359.
    Nayfach S. et al. (2021) A genomic catalog of Earth’s microbiomes. Nature Biotechnology 39: 499–509. [PMC free article: PMC8041624] [PubMed: 33169036]
    360.
    Pham V.H.T. and Kim J. (2012) Cultivation of unculturable soil bacteria. Trends in Biotechnology 30: 475–484. [PubMed: 22770837]
    361.
    Browne H.P. et al. (2016) Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature 533: 543–546. [PMC free article: PMC4890681] [PubMed: 27144353]
    362.
    Brüssow H. (2009) The not so universal tree of life or the place of viruses in the living world. Philosophical Transactions of the Royal Society B: Biological Sciences 364: 2263–2274. [PMC free article: PMC2873004] [PubMed: 19571246]
    363.
    Koonin E.V. (2009) On the origin of cells and viruses. Annals of the New York Academy of Sciences 1178: 47–64. [PMC free article: PMC3380365] [PubMed: 19845627]
    364.
    Nasir A., Kim K.M. and Caetano-Anolles G. (2012) Giant viruses coexisted with the cellular ancestors and represent a distinct supergroup along with superkingdoms Archaea, Bacteria and Eukarya. BMC Evolutionary Biology 12: 156. [PMC free article: PMC3570343] [PubMed: 22920653]
    365.
    Claverie J.-M. (2006) Viruses take center stage in cellular evolution. Genome Biology 7: 110. [PMC free article: PMC1779534] [PubMed: 16787527]
    366.
    Gregory A.C. et al. (2019) Marine DNA viral macro- and microdiversity from pole to pole. Cell 177: 1109–1123. [PMC free article: PMC6525058] [PubMed: 31031001]
    367.
    Turnbaugh P.J. et al. (2007) The human microbiome project. Nature 449: 804 –10. [PMC free article: PMC3709439] [PubMed: 17943116]
    368.
    Ochoa-Repáraz J. et al. (2009) Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. Journal of Immunology 183: 6041–6050. [PubMed: 19841183]
    369.
    De Vadder F. et al. (2014) Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156: 84–96. [PubMed: 24412651]
    370.
    Singh V. et al. (2016) Microbiota dysbiosis controls the neuroinflammatory response after stroke. Journal of Neuroscience 36: 7428–7440. [PMC free article: PMC6705544] [PubMed: 27413153]
    371.
    Olson C.A. et al. (2018) The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell 173: 1728–1741. [PMC free article: PMC6003870] [PubMed: 29804833]
    372.
    Valdes A.M., Walter J., Segal E. and Spector T.D. (2018) Role of the gut microbiota in nutrition and health. British Medical Journal 361: j2179. [PMC free article: PMC6000740] [PubMed: 29899036]
    373.
    Ding R-X, et al. (2019) Revisit gut microbiota and its impact on human health and disease. Journal of Food and Drug Analysis 27: 623–631. [PMC free article: PMC9307029] [PubMed: 31324279]
    374.
    Chen P.B. et al. (2020) Directed remodeling of the mouse gut microbiome inhibits the development of atherosclerosis. Nature Biotechnology 38: 1288–1297. [PMC free article: PMC7641989] [PubMed: 32541956]
    375.
    Hsiao E.Y. et al. (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155: 1451–1463. [PMC free article: PMC3897394] [PubMed: 24315484]
    376.
    Sampson T.R. et al. (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s Disease. Cell 167: 1469–1480. [PMC free article: PMC5718049] [PubMed: 27912057]
    377.
    Kim S. et al. (2017) Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature 549: 528–532. [PMC free article: PMC5870873] [PubMed: 28902840]
    378.
    Gerhardt S. and Mohajeri M.H. (2018) Changes of colonic bacterial composition in Parkinson’s Disease and other neurodegenerative diseases. Nutrients 10: 708. [PMC free article: PMC6024871] [PubMed: 29857583]
    379.
    Clarke G. et al. (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Molecular Psychiatry 18: 666–673. [PubMed: 22688187]
    380.
    Yano J.M. et al. (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161: 264–276. [PMC free article: PMC4393509] [PubMed: 25860609]
    381.
    Desbonnet L., Clarke G., Shanahan F., Dinan T.G. and Cryan J.F. (2014) Microbiota is essential for social development in the mouse. Molecular Psychiatry 19: 146–148. [PMC free article: PMC3903109] [PubMed: 23689536]
    382.
    Buffington S.A. et al. (2016) Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell 165: 1762–1775. [PMC free article: PMC5102250] [PubMed: 27315483]
    383.
    Valles-Colomer M. et al. (2019) The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology 4: 623–632. [PubMed: 30718848]
    384.
    O’Donnell M.P., Fox B.W., Chao P.-H., Schroeder F.C. and Sengupta P. (2020) A neurotransmitter produced by gut bacteria modulates host sensory behaviour. Nature 583: 415–420. [PMC free article: PMC7853625] [PubMed: 32555456]
    385.
    Schretter C.E. et al. (2018) A gut microbial factor modulates locomotor behaviour in Drosophila. Nature 563: 402–406. [PMC free article: PMC6237646] [PubMed: 30356215]
    386.
    Sudo N. et al. (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. Journal of Physiology 558: 263–275. [PMC free article: PMC1664925] [PubMed: 15133062]
    387.
    Turnbaugh P.J. et al. (2009) A core gut microbiome in obese and lean twins. Nature 457: 480–484. [PMC free article: PMC2677729] [PubMed: 19043404]
    388.
    Barr J.J. et al. (2013) Bacteriophage adhering to mucus provide a non–host-derived immunity. Proceedings of the National Academy of Sciences USA 110: 10771–10776. [PMC free article: PMC3696810] [PubMed: 23690590]
    389.
    Proctor L.M. et al. (2019) The integrative human microbiome project. Nature 569: 641–648. [PMC free article: PMC6784865] [PubMed: 31142853]
    390.
    Burki F., Roger A.J., Brown M.W. and Simpson A.G.B. (2020) The new tree of Eukaryotes. Trends in Ecology & Evolution 35: 43–55. [PubMed: 31606140]
    391.
    Matasci N. et al. (2014) Data access for the 1,000 Plants (1KP) project. GigaScience 3: 17. [PMC free article: PMC4306014] [PubMed: 25625010]
    392.
    Chen F. et al. (2018) The sequenced angiosperm genomes and genome databases. Frontiers in Plant Science 9: 418. [PMC free article: PMC5909171] [PubMed: 29706973]
    393.
    Leebens-Mack J.H. et al. (2019) One thousand plant transcriptomes and the phylogenomics of green plants. Nature 574: 679–685. [PMC free article: PMC6872490] [PubMed: 31645766]
    394.
    Koepfli K.-P., Benedict Paten, Genome 10K Community of Scientists and O’Brien S.J. (2015) The Genome 10K Project: A way forward. Annual Review of Animal Biosciences 3: 57–111. [PMC free article: PMC5837290] [PubMed: 25689317]
    395.
    Rhie A. et al. (2021) Towards complete and error-free genome assemblies of all vertebrate species. Nature 592: 737–746. [PMC free article: PMC8081667] [PubMed: 33911273]
    396.
    Lewin H.A. et al. (2018) Earth BioGenome project: Sequencing life for the future of life. Proceedings of the National Academy of Sciences USA 115: 4325–4333. [PMC free article: PMC5924910] [PubMed: 29686065]
    397.
    Zhang J., Cong Q., Shen J., Opler P.A. and Grishin N.V. (2019) Genomics of a complete butterfly continent. bioRxiv: 829887.
    398.
    Ellis E.A., Storer C.G. and Kawahara A.Y. (2021) De novo genome assemblies of butterflies. GigaScience 10: 1–8. [PMC free article: PMC8170690] [PubMed: 34076242]
    399.
    Genereux D.P. et al. (2020) A comparative genomics multitool for scientific discovery and conservation. Nature 587: 240–245. [PMC free article: PMC7759459] [PubMed: 33177664]
    400.
    Feng S. et al. (2020) Dense sampling of bird diversity increases power of comparative genomics. Nature 587: 252–257. [PMC free article: PMC7759463] [PubMed: 33177665]
    401.
    Tettelin H. et al. (2005) Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: Implications for the microbial “pan-genome”. Proceedings of the National Academy of Sciences USA 102: 13950–13955. [PMC free article: PMC1216834] [PubMed: 16172379]
    402.
    Morgante M., De Paoli E. and Radovic S. (2007) Transposable elements and the plant pan-genomes. Current Opinion in Plant Biology 10: 149–155. [PubMed: 17300983]
    403.
    Sherman R.M. and Salzberg S.L. (2020) Pan-genomics in the human genome era. Nature Reviews Genetics 21: 243–254. [PMC free article: PMC7752153] [PubMed: 32034321]
    404.
    Kent W.J., Baertsch R., Hinrichs A., Miller W. and Haussler D. (2003) Evolution’s cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes. Proceedings of the National Academy of Sciences USA 100: 11484–11489. [PMC free article: PMC208784] [PubMed: 14500911]
    405.
    Margulies E.H. et al. (2005) Comparative sequencing provides insights about the structure and conservation of marsupial and monotreme genomes. Proceedings of the National Academy of Sciences USA 102: 3354–3359. [PMC free article: PMC549084] [PubMed: 15718282]
    406.
    Hughes L.C. et al. (2018) Comprehensive phylogeny of ray-finned fishes (Actinopterygii) based on transcriptomic and genomic data. Proceedings of the National Academy of Sciences USA 115: 6249–6254. [PMC free article: PMC6004478] [PubMed: 29760103]
    407.
    Armstrong J. et al. (2020) Progressive Cactus is a multiple-genome aligner for the thousand-genome era. Nature 587: 246–251. [PMC free article: PMC7673649] [PubMed: 33177663]
    408.
    Green R.E. et al. (2010) A draft sequence of the Neandertal genome. Science 328: 710–722. [PMC free article: PMC5100745] [PubMed: 20448178]
    409.
    Fu Q. et al. (2014) Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514: 445–449. [PMC free article: PMC4753769] [PubMed: 25341783]
    410.
    Prüfer K. et al. (2014) The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505: 43–49. [PMC free article: PMC4031459] [PubMed: 24352235]
    411.
    Pääbo S. (2014) The human condition—a molecular approach. Cell 157: 216–226. [PubMed: 24679537]
    412.
    Sankararaman S., Mallick S., Patterson N. and Reich D. (2016) The combined landscape of Denisovan and Neanderthal ancestry in present-day humans. Current Biology 26: 1241–1247. [PMC free article: PMC4864120] [PubMed: 27032491]
    413.
    Schaefer N.K., Shapiro B. and Green R.E. (2021) An ancestral recombination graph of human, Neanderthal, and Denisovan genomes. Science Advances 7: eabc0776. [PMC free article: PMC8284891] [PubMed: 34272242]
    414.
    Bergström A. et al. (2020) Insights into human genetic variation and population history from 929 diverse genomes. Science 367: eaay5012. [PMC free article: PMC7115999] [PubMed: 32193295]
    415.
    Serre D. and Pääbo S. (2004) Evidence for gradients of human genetic diversity within and among continents. Genome Research 14: 1679–1685. [PMC free article: PMC515312] [PubMed: 15342553]
    416.
    Schuster S.C. et al. (2010) Complete Khoisan and Bantu genomes from southern Africa. Nature 463: 943–947. [PMC free article: PMC3890430] [PubMed: 20164927]
    417.
    Skoglund P. and Mathieson I. (2018) Ancient genomics of modern humans: The first decade. Annual Review of Genomics and Human Genetics 19: 381–404. [PubMed: 29709204]
    418.
    Chan E.K.F. et al. (2019) Human origins in a southern African palaeo-wetland and first migrations. Nature 575: 185–189. [PubMed: 31659339]
    419.
    Choudhury A. et al. (2020) High-depth African genomes inform human migration and health. Nature 586: 741–748. [PMC free article: PMC7759466] [PubMed: 33116287]
    420.
    Taliun D. et al. (2021) Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature 590: 290–299. [PMC free article: PMC7875770] [PubMed: 33568819]
    421.
    Anava S. et al. (2020) Illuminating genetic mysteries of the dead sea scrolls. Cell 181: 1218–1231. [PubMed: 32492404]
    422.
    van der Valk T. et al. (2021) Million-year-old DNA sheds light on the genomic history of mammoths. Nature 591: 265–269. [PMC free article: PMC7116897] [PubMed: 33597750]
    423.
    Barlow A. et al. (2021) Middle Pleistocene genome calibrates a revised evolutionary history of extinct cave bears. Current Biology 31: 1771–1779. [PubMed: 33592193]

    Chapter 11

    1.
    Sinsheimer R.L. (2006) To reveal the genomes. American Journal of Human Genetics 79: 194–196. [PMC free article: PMC1559495] [PubMed: 16826511]
    2.
    Dulbecco R. (1986) A turning point in cancer research: Sequencing the human genome. Science 231: 1055–1056. [PubMed: 3945817]
    3.
    Sinsheimer R.L. (1989) The santa cruz workshop—May 1985. Genomics 5: 954–956. [PubMed: 2591974]
    4.
    5.
    DeLisi C. (2008) Meetings that changed the world: Santa Fe 1986: Human genome baby-steps. Nature 455: 876–877. [PubMed: 18923499]
    6.
    Tinoco I. et al. (1987) Report on the Human Genome Initiative, Office of Health and Environmental Research, prepared for Dr. Alvin W. Trivelpiece, Director, Office of Energy Research, https://web​.ornl.gov​/sci/techresources/Human_Genome​/project/herac2.shtml.
    7.
    Roberts L. (2001) Controversial from the start. Science 291: 1182–1188. [PubMed: 11233424]
    8.
    Berg P. (2006) Origins of the human genome project: Why sequence the human genome when 96% of it is junk? American Journal of Human Genetics 79: 603–605. [PMC free article: PMC1592577] [PubMed: 16960796]
    9.
    Rechsteiner M.C. (1991) The human genome project: Misguided science policy. Trends in Biochemical Sciences 16: 455–461. [PubMed: 1781023]
    10.
    Brenner S. (2007) The human genome: The nature of the enterprise. Ciba Foundation Symposium 149 ‐ Human Genetic Information: Science, Law and Ethics 149: 6–12. [PubMed: 2335125]
    11.
    Sinsheimer R.L. (1986) Human genome sequencing. Science 233: 1246. [PubMed: 17843345]
    12.
    Wheeler D.A. et al. (2008) The complete genome of an individual by massively parallel DNA sequencing. Nature 452: 872–876. [PubMed: 18421352]
    13.
    Watson J.D. (1990) The human genome project: Past, present, and future. Science 248: 44–49. [PubMed: 2181665]
    14.
    Vogel F. (1964) A preliminary estimate of the number of human genes. Nature 201: 847. [PubMed: 14161239]
    15.
    King J.L. and Jukes T.H. (1969) Non-Darwinian evolution. Science 164: 788–798. [PubMed: 5767777]
    16.
    Ohno S. (1972) An argument for the genetic simplicity of man and other mammals. Journal of Human Evolution 1: 651–662.
    17.
    Fields C., Adams M.D., White O. and Venter J.C. (1994) How many genes in the human genome? Nature Genetics 7: 345–346. [PubMed: 7920649]
    18.
    Goodfellow P. (1995) A big book of the human genome. Nature 377: 285–286. [PubMed: 7566079]
    19.
    Schuler G.D. (1997) Pieces of the puzzle: Expressed sequence tags and the catalog of human genes. Journal of Molecular Medicine 75: 694–698. [PubMed: 9382993]
    20.
    Maxson Jones K., Ankeny R.A. and Cook-Deegan R. (2018) The Bermuda Triangle: The pragmatics, policies, and principles for data sharing in the history of the Human Genome Project. Journal of the History of Biology 51: 693–805. see alsohttps://web​.ornl.gov​/sci/techresources/Human_Genome​/research/bermuda.shtml. [PMC free article: PMC7307446] [PubMed: 30390178]
    21.
    Morgan M.J. (2011) A brief (if insular) history of the human genome project. PLOS Biology 9: e1000601.
    22.
    Cook-Deegan R. and McGuire A.L. (2017) Moving beyond Bermuda: Sharing data to build a medical information commons. Genome Research 27: 897–901. [PMC free article: PMC5453323] [PubMed: 28373484]
    23.
    Waterston R.H., Lander E.S. and Sulston J.E. (2002) On the sequencing of the human genome. Proceedings of the National Academy of Sciences USA 99: 3712–3716. [PMC free article: PMC122589] [PubMed: 11880605]
    24.
    Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921. [PubMed: 11237011]
    25.
    Venter J.C. et al. (2001) The sequence of the human genome. Science 291: 1304–1351. [PubMed: 11181995]
    26.
    Internation Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431: 931–945. [PubMed: 15496913]
    27.
    Piovesan A., Caracausi M., Antonaros F., Pelleri M.C. and Vitale L. (2016) GeneBase 1.1: A tool to summarize data from NCBI gene datasets and its application to an update of human gene statistics. Database 2016: baw153. [PMC free article: PMC5199132] [PubMed: 28025344]
    28.
    Pertea M. and Salzberg S.L. (2010) Between a chicken and a grape: Estimating the number of human genes. Genome Biology 11: 206. [PMC free article: PMC2898077] [PubMed: 20441615]
    29.
    Willyard C. (2018) New human gene tally reignites debate. Nature 558: 354–355. [PubMed: 29921859]
    30.
    Gates A.J., Gysi D.M., Kellis M. and Barabási A.-L. (2021) A wealth of discovery built on the Human Genome Project — by the numbers. Nature 590: 212–215. [PubMed: 33568828]
    31.
    Aparicio S. et al. (2002) Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science 297: 1301–1310. [PubMed: 12142439]
    32.
    Hillier L.W. et al. (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432: 695–716. [PubMed: 15592404]
    33.
    Duboule D. and Wilkins A.S. (1998) The evolution of ‘bricolage’. Trends in Genetics 14: 54–59. [PubMed: 9520598]
    34.
    Waterston R.H. et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562. [PubMed: 12466850]
    35.
    Smith N.G.C., Webster M.T. and Ellegren H. (2002) Deterministic mutation rate variation in the human genome. Genome Research 12: 1350–1356. [PMC free article: PMC186654] [PubMed: 12213772]
    36.
    Smith N.G., Brandstrom M. and Ellegren H. (2004) Evidence for turnover of functional noncoding DNA in mammalian genome evolution. Genomics 84: 806–813. [PubMed: 15475259]
    37.
    Arndt P.F., Hwa T. and Petrov D.A. (2005) Substantial regional variation in substitution rates in the human genome: Importance of GC content, gene density, and telomere-specific effects. Journal of Molecular Evolution 60: 748–763. [PubMed: 15959677]
    38.
    Duret L. (2009) Mutation patterns in the human genome: More variable than expected. PLOS Biology 7: e1000028. [PMC free article: PMC2634789] [PubMed: 19192948]
    39.
    Graur D. et al. (2013) On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of encode. Genome Biology and Evolution 5: 578–590. [PMC free article: PMC3622293] [PubMed: 23431001]
    40.
    Mattick J.S. and Dinger M.E. (2013) The extent of functionality in the human genome. HUGO Journal 7: 2.
    41.
    Pheasant M. and Mattick J.S. (2007) Raising the estimate of functional human sequences. Genome Research 17: 1245–1253. [PubMed: 17690206]
    42.
    Smit A.F.A. (1999) Interspersed repeats and other mementos of transposable elements in mammalian genomes. Current Opinion in Genetics and Development 9: 657–663. [PubMed: 10607616]
    43.
    Silva J.C., Shabalina S.A., Harris D.G., Spouge J.L. and Kondrashovi A.S. (2003) Conserved fragments of transposable elements in intergenic regions: Evidence for widespread recruitment of MIR- and L2-derived sequences within the mouse and human genomes. Genetics Research 82: 1–18. [PubMed: 14621267]
    44.
    de Koning A.P.J., Gu W., Castoe T.A., Batzer M.A. and Pollock D.D. (2011) Repetitive elements may comprise over two-thirds of the human genome. PLOS Genetics 7: e1002384. [PMC free article: PMC3228813] [PubMed: 22144907]
    45.
    Hubley R. et al. (2016) The Dfam database of repetitive DNA families. Nucleic Acids Research 44: D81–9. [PMC free article: PMC4702899] [PubMed: 26612867]
    46.
    Pang K.C. et al. (2007) RNAdb 2.0–an expanded database of mammalian non-coding RNAs. Nucleic Acids Research 35: D178–82. [PMC free article: PMC1751534] [PubMed: 17145715]
    47.
    Taylor M.S. et al. (2006) Heterotachy in mammalian promoter evolution. PLOS Genetics 2: e30. [PMC free article: PMC1449885] [PubMed: 16683025]
    48.
    Vierstra J. et al. (2020) Global reference mapping of human transcription factor footprints. Nature 583: 729–736. [PMC free article: PMC7410829] [PubMed: 32728250]
    49.
    Ross C.J. et al. (2021) Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences. Genome Biology 22: 29. [PMC free article: PMC7798263] [PubMed: 33430943]
    50.
    Wong E.S. et al. (2020) Deep conservation of the enhancer regulatory code in animals. Science 370: eaax8137. [PubMed: 33154111]
    51.
    Oldmeadow C., Mengersen K., Mattick J.S. and Keith J.M. (2010) Multiple evolutionary rate classes in animal genome evolution. Molecular Biology and Evolution 27: 942–953. [PubMed: 19955480]
    52.
    Smith M.A., Gesell T., Stadler P.F. and Mattick J.S. (2013) Widespread purifying selection on RNA structure in mammals. Nucleic Acids Research 41: 8220–8236. [PMC free article: PMC3783177] [PubMed: 23847102]
    53.
    Gazal S. et al. (2018) Functional architecture of low-frequency variants highlights strength of negative selection across coding and non-coding annotations. Nature Genetics 50: 1600–1607. [PMC free article: PMC6236676] [PubMed: 30297966]
    54.
    Feng S. et al. (2020) Dense sampling of bird diversity increases power of comparative genomics. Nature 587: 252–257. [PMC free article: PMC7759463] [PubMed: 33177665]
    55.
    The ENCODE Project Consortium (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447: 799–816. [PMC free article: PMC2212820] [PubMed: 17571346]
    56.
    Giresi P.G., Kim J., McDaniell R.M., Iyer V.R. and Lieb J.D. (2007) FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Research 17: 877–885. [PMC free article: PMC1891346] [PubMed: 17179217]
    57.
    Check E. (2007) Genome project turns up evolutionary surprises. Nature 447: 760–761. [PubMed: 17568710]
    58.
    Thurman R.E. et al. (2012) The accessible chromatin landscape of the human genome. Nature 489: 75–82. [PMC free article: PMC3721348] [PubMed: 22955617]
    59.
    Djebali S. et al. (2012) Landscape of transcription in human cells. Nature 489: 101–108. [PMC free article: PMC3684276] [PubMed: 22955620]
    60.
    Dunham I. et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74. [PMC free article: PMC3439153] [PubMed: 22955616]
    61.
    Editorial (2014) ENCODE debate revived online. Nature 509: 137.
    62.
    Germain P.-L., Ratti E. and Boem F. (2014) Junk or functional DNA? ENCODE and the function controversy. Biology & Philosophy 29: 807–831.
    63.
    Eddy S.R. (2012) The C-value paradox, junk DNA and ENCODE. Current Biology 22: R898–9. [PubMed: 23137679]
    64.
    Doolittle W.F. (2013) Is junk DNA bunk? A critique of ENCODE. Proceedings of the National Academy of Sciences USA 110: 5294–5300. [PMC free article: PMC3619371] [PubMed: 23479647]
    65.
    Davidson D.J. and Porteous D.J. (1998) The genetics of cystic fibrosis lung disease. Thorax 53: 389–397. [PMC free article: PMC1745224] [PubMed: 9708232]
    66.
    Poolman E.M. and Galvani A.P. (2007) Evaluating candidate agents of selective pressure for cystic fibrosis. Journal of the Royal Society Interface 4: 91–98. [PMC free article: PMC2358959] [PubMed: 17015291]
    67.
    Ferreira A. et al. (2011) Sickle hemoglobin confers tolerance to Plasmodium infection. Cell 145: 398–409. [PubMed: 21529713]
    68.
    Mattick J.S. (2009) The genetic signatures of noncoding RNAs. PLOS Genetics 5: e1000459. [PMC free article: PMC2667263] [PubMed: 19390609]
    69.
    Solomon E. and Bodmer W.F. (1979) Evolution of sickle variant gene. Lancet 313: 923. [PubMed: 86686]
    70.
    Botstein D., White R.L., Skolnick M. and Davis R.W. (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. American Journal of Human Genetics 32: 314–331. [PMC free article: PMC1686077] [PubMed: 6247908]
    71.
    Simons M.J. (2001) Intron sequence analysis method for detection of adjacent and remote locus alleles as haplotypes. US patent US20010005626.
    72.
    Lander E.S. and Botstein D. (1986) Strategies for studying heterogeneous genetic traits in humans by using a linkage map of restriction fragment length polymorphisms. Proceedings of the National Academy of Sciences USA 83: 7353–7357. [PMC free article: PMC386715] [PubMed: 2876423]
    73.
    Davies K.E., Young B.D., Elles R.G., Hill M.E. and Williamson R. (1981) Cloning of a representative genomic library of the human X chromosome after sorting by flow cytometry. Nature 293: 374–376. [PubMed: 6456416]
    74.
    Krumlauf R., Jeanpierre M. and Young B.D. (1982) Construction and characterization of genomic libraries from specific human chromosomes. Proceedings of the National Academy of Sciences USA 79: 2971–2975. [PMC free article: PMC346330] [PubMed: 6953442]
    75.
    Nabholz M., Miggiano V. and Bodmer W. (1969) Genetic analysis with human—mouse somatic cell hybrids. Nature 223: 358–363. [PubMed: 4309885]
    76.
    Goss S.J. and Harris H. (1975) New method for mapping genes in human chromosomes. Nature 255: 680–684. [PubMed: 1169690]
    77.
    Cox D., Burmeister M., Price E., Kim S. and Myers R. (1990) Radiation hybrid mapping: A somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. Science 250: 245–250. [PubMed: 2218528]
    78.
    Frazer K.A. et al. (1992) A radiation hybrid map of the region on human chromosome 22 containing the neurofibromatosis type 2 locus. Genomics 14: 574–584. [PubMed: 1427886]
    79.
    Zengerling S. et al. (1987) Mapping of DNA markers linked to the cystic fibrosis locus on the long arm of chromosome 7. American Journal of Human Genetics 40: 228–236. [PMC free article: PMC1684102] [PubMed: 3472464]
    80.
    Frazer K.A. et al. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851–861. [PMC free article: PMC2689609] [PubMed: 17943122]
    81.
    Arnheim N., Calabrese P. and Tiemann-Boege I. (2007) Mammalian meiotic recombination hot spots. Annual Review of Genetics 41: 369–399. [PubMed: 18076329]
    82.
    Wall J.D. and Pritchard J.K. (2003) Haplotype blocks and linkage disequilibrium in the human genome. Nature Reviews Genetics 4: 587–597. [PubMed: 12897771]
    83.
    Buetow K.H. et al. (1994) Integrated human genome–wide maps constructed using the CEPH reference panel. Nature Genetics 6: 391–393. [PubMed: 8054980]
    84.
    Gabriel S.B. et al. (2002) The structure of haplotype blocks in the human genome. Science 296: 2225–2229. [PubMed: 12029063]
    85.
    Cardon L.R. and Abecasis G.R. (2003) Using haplotype blocks to map human complex trait loci. Trends in Genetics 19: 135–140. [PubMed: 12615007]
    86.
    Lander E. and Botstein D. (1987) Homozygosity mapping: A way to map human recessive traits with the DNA of inbred children. Science 236: 1567–1570. [PubMed: 2884728]
    87.
    Monaco A.P. et al. (1986) Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 323: 646–650. [PubMed: 3773991]
    88.
    Koenig M. et al. (1987) Complete cloning of the duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50: 509–517. [PubMed: 3607877]
    89.
    Hoffman E.P. (2020) The discovery of dystrophin, the protein product of the Duchenne muscular dystrophy gene. FEBS Journal 287: 3879–3887. [PMC free article: PMC7540009] [PubMed: 32608079]
    90.
    Ahn A.H. and Kunkel L.M. (1993) The structural and functional diversity of dystrophin. Nature Genetics 3: 283–291. [PubMed: 7981747]
    91.
    Pozzoli U. et al. (2003) Comparative analysis of vertebrate dystrophin loci indicate intron gigantism as a common feature. Genome Research 13: 764–772. [PMC free article: PMC430921] [PubMed: 12727896]
    92.
    Kerem B. et al. (1989) Identification of the cystic fibrosis gene: Genetic analysis. Science 245: 1073–1080. [PubMed: 2570460]
    93.
    Tsui L.-C. and Dorfman R. (2013) The cystic fibrosis gene: A molecular genetic perspective. Cold Spring Harbor Perspectives in Medicine 3: a009472. [PMC free article: PMC3552342] [PubMed: 23378595]
    94.
    van Deutekom J.C. et al. (2001) Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells. Human Molecular Genetics 10: 1547–1554. [PubMed: 11468272]
    95.
    Mann C.J. et al. (2001) Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse. Proceedings of the National Academy of Sciences USA 98: 42–47. [PMC free article: PMC14541] [PubMed: 11120883]
    96.
    De Angelis F.G. et al. (2002) Chimeric snRNA molecules carrying antisense sequences against the splice junctions of exon 51 of the dystrophin pre-mRNA induce exon skipping and restoration of a dystrophin synthesis in Delta 48–50 DMD cells. Proceedings of the National Academy of Sciences USA 99: 9456–9461. [PMC free article: PMC123162] [PubMed: 12077324]
    97.
    Cirak S. et al. (2011) Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: An open-label, phase 2, dose-escalation study. Lancet 378: 595–605. [PMC free article: PMC3156980] [PubMed: 21784508]
    98.
    Lee T.W.R., Matthews D.A. and Blair G.E. (2005) Novel molecular approaches to cystic fibrosis gene therapy. Biochemical Journal 387: 1–15. [PMC free article: PMC1134927] [PubMed: 15656784]
    99.
    Cooney A.L., McCray Jr. P.B. and Sinn P.L. (2018) Cystic fibrosis gene therapy: Looking back, looking forward. Genes 9: 538. [PMC free article: PMC6266271] [PubMed: 30405068]
    100.
    Verkerk A.J.M.H. et al. (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65: 905–914. [PubMed: 1710175]
    101.
    Oberle I. et al. (1991) Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252: 1097–1102. [PubMed: 2031184]
    102.
    Hagerman R.J. et al. (2017) Fragile X syndrome. Nature Reviews Disease Primers 3: 17065. [PubMed: 28960184]
    103.
    Spada A.R.L., Wilson E.M., Lubahn D.B., Harding A.E. and Fischbeck K.H. (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352: 77–79. [PubMed: 2062380]
    104.
    Brook J.D. et al. (1992) Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 68: 799–808. [PubMed: 1310900]
    105.
    Liquori C.L. et al. (2001) Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 293: 864–867. [PubMed: 11486088]
    106.
    MacDonald M.E. et al. (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72: 971–983. [PubMed: 8458085]
    107.
    Orr H.T. et al. (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nature Genetics 4: 221–226. [PubMed: 8358429]
    108.
    Koide R. et al. (1994) Unstable expansion of CAG repeat in hereditary dentatorubral–pallidoluysian atrophy (DRPLA). Nature Genetics 6: 9–13. [PubMed: 8136840]
    109.
    Nagafuchi S. et al. (1994) Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nature Genetics 6: 14–18. [PubMed: 8136826]
    110.
    Kawaguchi Y. et al. (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nature Genetics 8: 221–228. [PubMed: 7874163]
    111.
    Cummings C.J. and Zoghbi H.Y. (2000) Fourteen and counting: Unraveling trinucleotide repeat diseases. Human Molecular Genetics 9: 909–916. [PubMed: 10767314]
    112.
    Bassani S. et al. (2013) The neurobiology of X-linked intellectual disability. Neuroscientist 19: 541–552. [PubMed: 23820068]
    113.
    Paulson H. (2018) Repeat expansion diseases, in D.H. Geschwind, H.L. Paulson and C. Klein (eds.) Handbook of Clinical Neurology (Elsevier, New York). [PMC free article: PMC6485936] [PubMed: 29325606]
    114.
    Robinson A. and Linden M.G. (2002) Clinical Genetics Handbook (Blackwell Scientific Publications, New York).
    115.
    van den Berg M.M.J., van Maarle M.C., van Wely M. and Goddijn M. (2012) Genetics of early miscarriage. Biochimica et Biophysica Acta 1822: 1951–1959. [PubMed: 22796359]
    116.
    Colley E. et al. (2019) Potential genetic causes of miscarriage in euploid pregnancies: A systematic review. Human Reproduction Update 25: 452–472. [PubMed: 31150545]
    117.
    McCandless S.E., Brunger J.W. and Cassidy S.B. (2004) The burden of genetic disease on inpatient care in a children’s hospital. American Journal of Human Genetics 74: 121–127. [PMC free article: PMC1181899] [PubMed: 14681831]
    118.
    Gjorgioski S. et al. (2020) Genetics and pediatric hospital admissions, 1985 to 2017. Genetics in Medicine 22: 1777–1785. [PubMed: 32555541]
    119.
    Rimoin D., Pyeritz R. and Korf B. (2022) Emery and Rimoin’s Principles and Practice of Medical Genetics, 7th edition (Elsevier, New York).
    120.
    Xue Y. et al. (2012) Deleterious- and disease-allele prevalence in healthy individuals: Insights from current predictions, mutation databases, and population-scale resequencing. American Journal of Human Genetics 91: 1022–1032. [PMC free article: PMC3516590] [PubMed: 23217326]
    121.
    Walter K. et al. (2015) The UK10K project identifies rare variants in health and disease. Nature 526: 82–90. [PMC free article: PMC4773891] [PubMed: 26367797]
    122.
    Lek M. et al. (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536: 285–291. [PMC free article: PMC5018207] [PubMed: 27535533]
    123.
    Fragoza R. et al. (2019) Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. Nature Communications 10: 4141. [PMC free article: PMC6742646] [PubMed: 31515488]
    124.
    Veltman J.A. and Brunner H.G. (2012) De novo mutations in human genetic disease. Nature Reviews Genetics 13: 565–575. [PubMed: 22805709]
    125.
    Mir Y.R. and Kuchay R.A.H. (2019) Advances in identification of genes involved in autosomal recessive intellectual disability: A brief review. Journal of Medical Genetics 56: 567–573. [PubMed: 30842223]
    126.
    Mattick J.S., Dinger M., Schonrock N. and Cowley M. (2018) Whole genome sequencing provides better diagnostic yield and future value than whole exome sequencing. Medical Journal of Australia 209: 197–199. [PubMed: 29621958]
    127.
    Zhang D. et al. (2020) Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders. Science Advances 6: eaay8299. [PMC free article: PMC7286675] [PubMed: 32917675]
    128.
    Smedley D. et al. (2021) 100,000 genomes pilot on rare-disease diagnosis in health care — preliminary report. New England Journal of Medicine 385: 1868–1880. [PMC free article: PMC7613219] [PubMed: 34758253]
    129.
    Murdock D.R. et al. (2021) Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing. Journal of Clinical Investigation 131: e141500. [PMC free article: PMC7773386] [PubMed: 33001864]
    130.
    Woolf L.I. and Adams J. (2020) The early history of PKU. International Journal of Neonatal Screening 6: 59. [PMC free article: PMC7570064] [PubMed: 33239585]
    131.
    Lo Y.M.D. et al. (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350: 485–487. [PubMed: 9274585]
    132.
    Lo Y.M.D. et al. (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: Implications for noninvasive prenatal diagnosis. American Journal of Human Genetics 62: 768–775. [PMC free article: PMC1377040] [PubMed: 9529358]
    133.
    Norwitz E.R. and Levy B. (2013) Noninvasive prenatal testing: The future is now. Reviews in Obstetrics & Gynecology 6: 48–62. [PMC free article: PMC3893900] [PubMed: 24466384]
    134.
    Mattick J.S. (2006) The future of molecular pathology, in S. Lakhani and S. Fox (eds.) Molecular Pathology in Cancer Research (Springer, New York).
    135.
    Cavalli-Sforza L.L. and Edwards A.W.F. (1967) Phylogenetic analysis: Models and estimation procedures. Evolution 21: 550–570. [PubMed: 28563688]
    136.
    Lewontin R.C. (1972) The apportionment of human diversity, in T. Dobzhansky, M.K. Hecht and W.C. Steere (eds.) Evolutionary Biology (Springer, New York).
    137.
    Rosenberg N.A. et al. (2002) Genetic structure of human populations. Science 298: 2381–2385. [PubMed: 12493913]
    138.
    Sabeti P.C. et al. (2007) Genome-wide detection and characterization of positive selection in human populations. Nature 449: 913–918. [PMC free article: PMC2687721] [PubMed: 17943131]
    139.
    Karczewski K.J. et al. (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581: 434–443. [PMC free article: PMC7334197] [PubMed: 32461654]
    140.
    Abecasis G.R. et al. (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491: 56–65. [PMC free article: PMC3498066] [PubMed: 23128226]
    141.
    Auton A. et al. (2015) A global reference for human genetic variation. Nature 526: 68–74. [PMC free article: PMC4750478] [PubMed: 26432245]
    142.
    Choudhury A. et al. (2020) High-depth African genomes inform human migration and health. Nature 586: 741–748. [PMC free article: PMC7759466] [PubMed: 33116287]
    143.
    Polderman T.J.C. et al. (2015) Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature Genetics 47: 702–709. [PubMed: 25985137]
    144.
    Sahu M. and Prasuna J.G. (2016) Twin studies: A unique epidemiological tool. Indian Journal of Community Medicine 41: 177–182. [PMC free article: PMC4919929] [PubMed: 27385869]
    145.
    Botstein D. and Risch N. (2003) Discovering genotypes underlying human phenotypes: Past successes for mendelian disease, future approaches for complex disease. Nature Genetics 33: 228–237. [PubMed: 12610532]
    146.
    Hirschhorn J.N. and Daly M.J. (2005) Genome-wide association studies for common diseases and complex traits. Nature Reviews Genetics 6: 95–108. [PubMed: 15716906]
    147.
    Schena M., Shalon D., Davis R.W. and Brown P.O. (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270: 467–470. [PubMed: 7569999]
    148.
    Gibson G. (2010) Hints of hidden heritability in GWAS. Nature Genetics 42: 558–560. [PubMed: 20581876]
    149.
    Clarke G.M. et al. (2011) Basic statistical analysis in genetic case-control studies. Nature Protocols 6: 121–133. [PMC free article: PMC3154648] [PubMed: 21293453]
    150.
    Ozaki K. et al. (2002) Functional SNPs in the lymphotoxin-α gene that are associated with susceptibility to myocardial infarction. Nature Genetics 32: 650–654. [PubMed: 12426569]
    151.
    Klein R.J. et al. (2005) Complement factor H polymorphism in Age-Related Macular Degeneration. Science 308: 385–389. [PMC free article: PMC1512523] [PubMed: 15761122]
    152.
    Burton P.R. et al. (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661–678. [PMC free article: PMC2719288] [PubMed: 17554300]
    153.
    Uda M. et al. (2008) Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of β-thalassemia. Proceedings of the National Academy of Sciences USA 105: 1620–1625. [PMC free article: PMC2234194] [PubMed: 18245381]
    154.
    Sankaran V.G. et al. (2008) Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science 322: 1839–1842. [PubMed: 19056937]
    155.
    Sankaran V.G. et al. (2011) A functional element necessary for fetal hemoglobin silencing. New England Journal of Medicine 365: 807–814. [PMC free article: PMC3174767] [PubMed: 21879898]
    156.
    Visscher P.M. et al. (2017) 10 years of GWAS discovery: Biology, function, and translation. American Journal of Human Genetics 101: 5–22. [PMC free article: PMC5501872] [PubMed: 28686856]
    157.
    Zwir I. et al. (2020) Uncovering the complex genetics of human temperament. Molecular Psychiatry 25: 2275–2294. [PMC free article: PMC7515831] [PubMed: 30279457]
    158.
    Grove J. et al. (2019) Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics 51: 431–444. [PMC free article: PMC6454898] [PubMed: 30804558]
    159.
    Narita A. et al. (2020) Clustering by phenotype and genome-wide association study in autism. Translational Psychiatry 10: 290. [PMC free article: PMC7431539] [PubMed: 32807774]
    160.
    Roussos P. et al. (2014) A role for noncoding variation in schizophrenia. Cell Reports 9: 1417–1429. [PMC free article: PMC4255904] [PubMed: 25453756]
    161.
    Zeng B. et al. (2022) Multi-ancestry eQTL meta-analysis of human brain identifies candidate causal variants for brain-related traits. Nature Genetics 54: 161–169. [PMC free article: PMC8852232] [PubMed: 35058635]
    162.
    Mullins N. et al. (2021) Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics 53: 817–829. [PMC free article: PMC8192451] [PubMed: 34002096]
    163.
    Demontis D. et al. (2019) Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics 51: 63–75. [PMC free article: PMC6481311] [PubMed: 30478444]
    164.
    Powell V., Martin J., Thapar A., Rice F. and Anney R.J.L. (2021) Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis. Scientific Reports 11: 7353. [PMC free article: PMC8016853] [PubMed: 33795730]
    165.
    Howard D.M. et al. (2019) Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nature Neuroscience 22: 343–352. [PMC free article: PMC6522363] [PubMed: 30718901]
    166.
    Forstner A.J. et al. (2021) Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression. Molecular Psychiatry 26: 4179–4190. [PubMed: 31712720]
    167.
    Levey D.F. et al. (2021) Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 24: 954–963. [PMC free article: PMC8404304] [PubMed: 34045744]
    168.
    Skuladottir A.T. et al. (2021) A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo. Communications Biology 4: 1148. [PMC free article: PMC8497462] [PubMed: 34620984]
    169.
    Jansen I.E. et al. (2019) Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nature Genetics 51: 404–413. [PMC free article: PMC6836675] [PubMed: 30617256]
    170.
    Andrews S.J., Fulton-Howard B. and Goate A. (2020) Interpretation of risk loci from genome-wide association studies of Alzheimer’s disease. Lancet Neurology 19: 326–335. [PMC free article: PMC8176461] [PubMed: 31986256]
    171.
    Grenn F.P. et al. (2020) The Parkinson’s Disease genome-wide association study locus browser. Movement Disorders 35: 2056–2067. [PMC free article: PMC7754106] [PubMed: 32864809]
    172.
    Sud A., Kinnersley B. and Houlston R.S. (2017) Genome-wide association studies of cancer: Current insights and future perspectives. Nature Reviews Cancer 17: 692–704. [PubMed: 29026206]
    173.
    Li Z. and Brown M.A. (2017) Progress of genome-wide association studies of ankylosing spondylitis. Clinical & Translational Immunology 6: e163. [PMC free article: PMC5750450] [PubMed: 29333268]
    174.
    Paternoster L. et al. (2015) Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nature Genetics 47: 1449–1456. [PMC free article: PMC4753676] [PubMed: 26482879]
    175.
    Dong Z. et al. (2020) Integrated genomics analysis highlights important SNPs and genes implicated in moderate-to-severe asthma based on GWAS and eQTL datasets. BMC Pulmonary Medicine 20: 270. [PMC free article: PMC7568423] [PubMed: 33066754]
    176.
    Momozawa Y. et al. (2018) IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes. Nature Communications 9: 2427. [PMC free article: PMC6013502] [PubMed: 29930244]
    177.
    Evangelou E. et al. (2018) Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nature Genetics 50: 1412–1425. [PMC free article: PMC6284793] [PubMed: 30224653]
    178.
    Yengo L. et al. (2018) Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry. Human Molecular Genetics 27: 3641–3649. [PMC free article: PMC6488973] [PubMed: 30124842]
    179.
    Zhu X., Bai W. and Zheng H. (2021) Twelve years of GWAS discoveries for osteoporosis and related traits: Advances, challenges and applications. Bone Research 9: 23. [PMC free article: PMC8085014] [PubMed: 33927194]
    180.
    Walters R.K. et al. (2018) Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. Nature Neuroscience 21: 1656–1669. [PMC free article: PMC6430207] [PubMed: 30482948]
    181.
    Kranzler H.R. et al. (2019) Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 10: 1499. [PMC free article: PMC6445072] [PubMed: 30940813]
    182.
    Liu M. et al. (2019) Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nature Genetics 51: 237–244. [PMC free article: PMC6358542] [PubMed: 30643251]
    183.
    Cabana-Domínguez J., Shivalikanjli A., Fernàndez-Castillo N. and Cormand B. (2019) Genome-wide association meta-analysis of cocaine dependence: Shared genetics with comorbid conditions. Progress in Neuro-Psychopharmacology and Biological Psychiatry 94: 109667. [PubMed: 31212010]
    184.
    Marees A.T. et al. (2020) Post-GWAS analysis of six substance use traits improves the identification and functional interpretation of genetic risk loci. Drug and Alcohol Dependence 206: 107703. [PMC free article: PMC9159918] [PubMed: 31785998]
    185.
    Cornelis M.C. et al. (2016) Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior. Human Molecular Genetics 25: 5472–5482. [PubMed: 27702941]
    186.
    Cuellar-Partida G. et al. (2021) Genome-wide association study identifies 48 common genetic variants associated with handedness. Nature Human Behaviour 5: 59–70. [PMC free article: PMC7116623] [PubMed: 32989287]
    187.
    Jansen P.R. et al. (2019) Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways. Nature Genetics 51: 394–403. [PubMed: 30804565]
    188.
    Deelen J. et al. (2019) A meta-analysis of genome-wide association studies identifies multiple longevity genes. Nature Communications 10: 3669. [PMC free article: PMC6694136] [PubMed: 31413261]
    189.
    Davies G. et al. (2018) Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nature Communications 9: 2098. [PMC free article: PMC5974083] [PubMed: 29844566]
    190.
    Davies G. et al. (2011) Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry 16: 996–1005. [PMC free article: PMC3182557] [PubMed: 21826061]
    191.
    Benyamin B. et al. (2014) Childhood intelligence is heritable, highly polygenic and associated with FNBP1L. Molecular Psychiatry 19: 253–258. [PMC free article: PMC3935975] [PubMed: 23358156]
    192.
    Davies G. et al. (2015) Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949). Molecular Psychiatry 20: 183–192. [PMC free article: PMC4356746] [PubMed: 25644384]
    193.
    Hill W.D. et al. (2019) A combined analysis of genetically correlated traits identifies 187 loci and a role for neurogenesis and myelination in intelligence. Molecular Psychiatry 24: 169–181. [PMC free article: PMC6344370] [PubMed: 29326435]
    194.
    Lee J.J. et al. (2018) Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nature Genetics 50: 1112–1121. [PMC free article: PMC6393768] [PubMed: 30038396]
    195.
    Boyle E.A., Li Y.I. and Pritchard J.K. (2017) An expanded view of complex traits: From polygenic to omnigenic. Cell 169: 1177–1186. [PMC free article: PMC5536862] [PubMed: 28622505]
    196.
    Young A.I. (2019) Solving the missing heritability problem. PLOS Genetics 15: e1008222. [PMC free article: PMC6611648] [PubMed: 31233496]
    197.
    Sohail M. et al. (2019) Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies. eLife 8: e39702. [PMC free article: PMC6428571] [PubMed: 30895926]
    198.
    NCD Risk Factor Collaboration (2016) A century of trends in adult human height. eLife 5: e13410. [PMC free article: PMC4961475] [PubMed: 27458798]
    199.
    Allen H.L. et al. (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467: 832–838. [PMC free article: PMC2955183] [PubMed: 20881960]
    200.
    Visscher P.M., McEvoy B. and Yang J. (2011) From Galton to GWAS: Quantitative genetics of human height. Genetics Research 92: 371–379. [PubMed: 21429269]
    201.
    Wainschtein P. et al. (2019) Recovery of trait heritability from whole genome sequence data. bioRxiv: 588020.
    202.
    Sackton T.B. and Hartl D.L. (2016) Genotypic context and epistasis in individuals and populations. Cell 166: 279–287. [PMC free article: PMC4948997] [PubMed: 27419868]
    203.
    Robinson M.R., Wray N.R. and Visscher P.M. (2014) Explaining additional genetic variation in complex traits. Trends in Genetics 30: 124–132. [PMC free article: PMC4639398] [PubMed: 24629526]
    204.
    Sinnott-Armstrong N., Naqvi S., Rivas M. and Pritchard J.K. (2021) GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background. eLife 10: e58615. [PMC free article: PMC7884075] [PubMed: 33587031]
    205.
    Yang J. et al. (2015) Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. Nature Genetics 47: 1114–1120. [PMC free article: PMC4589513] [PubMed: 26323059]
    206.
    Zeevi D. et al. (2019) Analysis of the genetic basis of height in large Jewish nuclear families. PLOS Genetics 15: e1008082. [PMC free article: PMC6638967] [PubMed: 31283753]
    207.
    Trost B. et al. (2020) Genome-wide detection of tandem DNA repeats that are expanded in autism. Nature 586: 80–86. [PMC free article: PMC9348607] [PubMed: 32717741]
    208.
    Mitra I. et al. (2021) Patterns of de novo tandem repeat mutations and their role in autism. Nature 589: 246–250. [PMC free article: PMC7810352] [PubMed: 33442040]
    209.
    Hannan A.J. (2021) Repeat DNA expands our understanding of autism spectrum disorder. Nature 589: 200–202. [PubMed: 33442037]
    210.
    Wilfert A.B. et al. (2021) Recent ultra-rare inherited variants implicate new autism candidate risk genes. Nature Genetics 53: 1125–1134. [PMC free article: PMC8459613] [PubMed: 34312540]
    211.
    Beroukhim R. et al. (2010) The landscape of somatic copy-number alteration across human cancers. Nature 463: 899–905. [PMC free article: PMC2826709] [PubMed: 20164920]
    212.
    Freedman M.L. et al. (2011) Principles for the post-GWAS functional characterization of cancer risk loci. Nature Genetics 43: 513–518. [PMC free article: PMC3325768] [PubMed: 21614091]
    213.
    Maurano M.T. et al. (2012) Systematic localization of common disease-associated variation in regulatory DNA. Science 337: 1190–1195. [PMC free article: PMC3771521] [PubMed: 22955828]
    214.
    Cheetham S.W., Gruhl F., Mattick J.S. and Dinger M.E. (2013) Long noncoding RNAs and the genetics of cancer. British Journal of Cancer 108: 2419–2425. [PMC free article: PMC3694235] [PubMed: 23660942]
    215.
    Zhang F. and Lupski J.R. (2015) Non-coding genetic variants in human disease. Human Molecular Genetics 24: R102–10. [PMC free article: PMC4572001] [PubMed: 26152199]
    216.
    Schierding W., Cutfield W. and O‘Sullivan J. (2014) The missing story behind Genome Wide Association Studies: Single nucleotide polymorphisms in gene deserts have a story to tell. Frontiers in Genetics 5: 39. [PMC free article: PMC3927098] [PubMed: 24600475]
    217.
    Gallagher M.D. and Chen-Plotkin A.S. (2018) The post-GWAS era: From association to function. American Journal of Human Genetics 102: 717–730. [PMC free article: PMC5986732] [PubMed: 29727686]
    218.
    Fagny M., Platig J., Kuijjer M.L., Lin X. and Quackenbush J. (2020) Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function. British Journal of Cancer 122: 569–577. [PMC free article: PMC7028992] [PubMed: 31806877]
    219.
    Padmanabhan S. and Dominiczak A.F. (2021) Genomics of hypertension: The road to precision medicine. Nature Reviews Cardiology 18: 235–250. [PubMed: 33219353]
    220.
    Watanabe K. et al. (2019) A global overview of pleiotropy and genetic architecture in complex traits. Nature Genetics 51: 1339–1348. [PubMed: 31427789]
    221.
    Vernot B. et al. (2012) Personal and population genomics of human regulatory variation. Genome Research 22: 1689–1697. [PMC free article: PMC3431486] [PubMed: 22955981]
    222.
    Trynka G. et al. (2013) Chromatin marks identify critical cell types for fine mapping complex trait variants. Nature Genetics 45: 124–130. [PMC free article: PMC3826950] [PubMed: 23263488]
    223.
    Bartonicek N. et al. (2017) Intergenic disease-associated regions are abundant in novel transcripts. Genome Biology 18: 241. [PMC free article: PMC5747244] [PubMed: 29284497]
    224.
    Hardwick S.A. et al. (2019) Targeted, high-resolution RNA sequencing of non-coding genomic regions associated with neuropsychiatric functions. Frontiers in Genetics 10: 309. [PMC free article: PMC6473190] [PubMed: 31031799]
    225.
    de Goede O.M. et al. (2021) Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease. Cell 184: 2633–2648. [PMC free article: PMC8651477] [PubMed: 33864768]
    226.
    Thomas J., Perron H. and Feschotte C. (2018) Variation in proviral content among human genomes mediated by LTR recombination. Mobile DNA 9: 36. [PMC free article: PMC6298018] [PubMed: 30568734]
    227.
    Hannan A.J. (2018) Tandem repeats mediating genetic plasticity in health and disease. Nature Reviews Genetics 19: 286–298. [PubMed: 29398703]
    228.
    Jendrzejewski J. et al. (2012) The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type. Proceedings of the National Academy of Sciences USA 109: 8646–8651. [PMC free article: PMC3365219] [PubMed: 22586128]
    229.
    Hnisz D. et al. (2013) Super-enhancers in the control of cell identity and disease. Cell 155: 934–947. [PMC free article: PMC3841062] [PubMed: 24119843]
    230.
    Lai F. et al. (2013) Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature 494: 497–501. [PMC free article: PMC4109059] [PubMed: 23417068]
    231.
    Smemo S. et al. (2014) Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507: 371–375. [PMC free article: PMC4113484] [PubMed: 24646999]
    232.
    Kim T. et al. (2014) Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. Proceedings of the National Academy of Sciences USA 111: 4173–4178. [PMC free article: PMC3964128] [PubMed: 24594601]
    233.
    St. Laurent G., Vyatkin Y. and Kapranov P. (2014) Dark matter RNA illuminates the puzzle of genome-wide association studies. BMC Medicine 12: 97. [PMC free article: PMC4054906] [PubMed: 24924000]
    234.
    Tan J.Y. et al. (2017) Cis-acting complex-trait-associated lincRNA expression correlates with modulation of chromosomal architecture. Cell Reports 18: 2280–2288. [PubMed: 28249171]
    235.
    Dong X. et al. (2018) Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease. Nature Neuroscience 21: 1482–1492. [PMC free article: PMC6334654] [PubMed: 30224808]
    236.
    Small K.S. et al. (2018) Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition. Nature Genetics 50: 572–580. [PMC free article: PMC5935235] [PubMed: 29632379]
    237.
    Rahman S. and Mansour M.R. (2019) The role of noncoding mutations in blood cancers. Disease Models & Mechanisms 12: dmm041988. [PMC free article: PMC6899015] [PubMed: 31771951]
    238.
    Ou M., Li X., Zhao S., Cui S. and Tu J. (2020) Long non-coding RNA CDKN2B-AS1 contributes to atherosclerotic plaque formation by forming RNA-DNA triplex in the CDKN2B promoter. EBioMedicine 55: 102694. [PMC free article: PMC7184162] [PubMed: 32335370]
    239.
    Ovcharenko I. et al. (2005) Evolution and functional classification of vertebrate gene deserts. Genome Research 15: 137–145. [PMC free article: PMC540279] [PubMed: 15590943]
    240.
    Ghoussaini M. et al. (2008) Multiple loci with different cancer specificities within the 8q24 gene desert. Journal of the National Cancer Institute 100: 962–966. [PMC free article: PMC2902819] [PubMed: 18577746]
    241.
    Huppi K., Pitt J., Wahlberg B. and Caplen N. (2012) The 8q24 gene desert: An oasis of non-coding transcriptional activity. Frontiers in Genetics 3: 69. [PMC free article: PMC3339310] [PubMed: 22558003]
    242.
    Hon C.-C. et al. (2017) An atlas of human long non-coding RNAs with accurate 5′ ends. Nature 543: 199–204. [PMC free article: PMC6857182] [PubMed: 28241135]
    243.
    Gandal M.J. et al. (2018) Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science 362: eaat8127. [PMC free article: PMC6443102] [PubMed: 30545856]
    244.
    Pasmant E., Sabbagh A., Vidaud M. and Bièche I. (2010) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB Journal 25: 444–448. [PubMed: 20956613]
    245.
    Castellanos-Rubio A. et al. (2016) A long noncoding RNA associated with susceptibility to celiac disease. Science 352: 91–95. [PMC free article: PMC4994711] [PubMed: 27034373]
    246.
    Ballantyne R.L. et al. (2016) Genome-wide interrogation reveals hundreds of long intergenic noncoding RNAs that associate with cardiometabolic traits. Human Molecular Genetics 25: 3125–3141. [PMC free article: PMC5181595] [PubMed: 27288454]
    247.
    Yuan H. et al. (2016) A novel genetic variant in long non-coding RNA gene NEXN-AS1 is associated with risk of lung cancer. Scientific Reports 6: 34234. [PMC free article: PMC5054367] [PubMed: 27713484]
    248.
    Guo H. et al. (2016) Modulation of long noncoding RNAs by risk SNPs underlying genetic predispositions to prostate cancer. Nature Genetics 48: 1142–1150. [PubMed: 27526323]
    249.
    Padua D. et al. (2016) A long noncoding RNA signature for ulcerative colitis identifies IFNG-AS1 as an enhancer of inflammation. American Journal of Physiology-Gastrointestinal and Liver Physiology 311: G446–G57. [PMC free article: PMC5076004] [PubMed: 27492330]
    250.
    Zhang D.-D. et al. (2017) Long noncoding RNA LINC00305 promotes inflammation by activating the AHRR-NF-κB pathway in human monocytes. Scientific Reports 7: 46204. [PMC free article: PMC5385552] [PubMed: 28393844]
    251.
    Holdt L.M. and Teupser D. (2018) Long noncoding RNA ANRIL: Lnc-ing genetic variation at the chromosome 9p21 locus to molecular mechanisms of atherosclerosis. Frontiers in Cardiovascular Medicine 5: 145. [PMC free article: PMC6232298] [PubMed: 30460243]
    252.
    Zhou J. et al. (2019) Whole-genome deep-learning analysis identifies contribution of noncoding mutations to autism risk. Nature Genetics 51: 973–980. [PMC free article: PMC6758908] [PubMed: 31133750]
    253.
    Ke W. et al. (2021) Genes in human obesity loci are causal obesity genes in C. elegans. PLOS Genetics 17: e1009736. [PMC free article: PMC8462697] [PubMed: 34492009]
    254.
    Saul M.C., Philip V.M., Reinholdt L.G. and Chesler E.J. (2019) High-diversity mouse populations for complex traits. Trends in Genetics 35: 501–514. [PMC free article: PMC6571031] [PubMed: 31133439]
    255.
    Kundaje A. et al. (2015) Integrative analysis of 111 reference human epigenomes. Nature 518: 317–330. [PMC free article: PMC4530010] [PubMed: 25693563]
    256.
    Krijger P.H.L. and de Laat W. (2016) Regulation of disease-associated gene expression in the 3D genome. Nature Reviews Molecular Cell Biology 17: 771–782. [PubMed: 27826147]
    257.
    Stunnenberg H.G. et al. (2016) The International Human Epigenome Consortium: A blueprint for scientific collaboration and discovery. Cell 167: 1145–1149. [PubMed: 27863232]
    258.
    Zeggini E., Gloyn A.L., Barton A.C. and Wain L.V. (2019) Translational genomics and precision medicine: Moving from the lab to the clinic. Science 365: 1409–1413. [PubMed: 31604268]
    259.
    Consortium (2020) The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369: 1318–1330. [PMC free article: PMC7737656] [PubMed: 32913098]
    260.
    Boix C.A., James B.T., Park Y.P., Meuleman W. and Kellis M. (2021) Regulatory genomic circuitry of human disease loci by integrative epigenomics. Nature 590: 300–307. [PMC free article: PMC7875769] [PubMed: 33536621]
    261.
    Yan J. et al. (2021) Systematic analysis of binding of transcription factors to noncoding variants. Nature 591: 147–151. [PMC free article: PMC9367673] [PubMed: 33505025]
    262.
    Julienne H. et al. (2021) Multitrait GWAS to connect disease variants and biological mechanisms. PLOS Genetics 17: e1009713. [PMC free article: PMC8437297] [PubMed: 34460823]
    263.
    264.
    Dudchenko O. et al. (2017) De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds. Science 356: 92–95. [PMC free article: PMC5635820] [PubMed: 28336562]
    265.
    Zhang J. et al. (2011) International Cancer Genome Consortium Data Portal—a one-stop shop for cancer genomics data. Database 2011: bar026. [PMC free article: PMC3263593] [PubMed: 21930502]
    266.
    Campbell P.J. et al. (2020) Pan-cancer analysis of whole genomes. Nature 578: 82–93. [PMC free article: PMC7025898] [PubMed: 32025007]
    267.
    Turnbull C. et al. (2018) The 100 000 Genomes Project: Bringing whole genome sequencing to the NHS. BMJ 361: k1687. [PubMed: 29691228]
    268.
    269.
    Denny J.C. et al. (2019) The “All of Us” research program. New England Journal of Medicine 381: 668–676. [PMC free article: PMC8291101] [PubMed: 31412182]
    270.
    Taliun D. et al. (2021) Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature 590: 290–299. [PMC free article: PMC7875770] [PubMed: 33568819]
    271.
    Momozawa Y. and Mizukami K. (2021) Unique roles of rare variants in the genetics of complex diseases in humans. Journal of Human Genetics 66: 11–23. [PMC free article: PMC7728599] [PubMed: 32948841]
    272.
    Koch E.M. and Sunyaev S.R. (2021) Maintenance of complex trait variation: Classic theory and modern data. Frontiers in Genetics 12: 2198. [PMC free article: PMC8636146] [PubMed: 34868244]
    273.
    Khera A.V. et al. (2018) Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nature Genetics 50: 1219–1224. [PMC free article: PMC6128408] [PubMed: 30104762]
    274.
    Weale M.E. et al. (2021) Validation of an integrated risk tool, including polygenic risk score, for atherosclerotic cardiovascular disease in multiple ethnicities and ancestries. American Journal of Cardiology 148: 157–164. [PubMed: 33675770]
    275.
    Riveros-Mckay F. et al. (2021) Integrated polygenic tool substantially enhances coronary artery disease prediction. Circulation: Genomic and Precision Medicine 14: e003304. [PMC free article: PMC8284388] [PubMed: 33651632]
    276.
    Wald N.J. and Old R. (2019) The illusion of polygenic disease risk prediction. Genetics in Medicine 21: 1705–1707. [PubMed: 30635622]
    277.
    David V. et al. (2021) An analysis of pharmacogenomic-guided pathways and their effect on medication changes and hospital admissions: A systematic review and meta-analysis. Frontiers in Genetics 12: 1308. [PMC free article: PMC8362615] [PubMed: 34394187]
    278.
    Berger M.F. and Mardis E.R. (2018) The emerging clinical relevance of genomics in cancer medicine. Nature Reviews Clinical oncology 15: 353–365. [PMC free article: PMC6658089] [PubMed: 29599476]
    279.
    Ding L. et al. (2018) Perspective on oncogenic processes at the end of the beginning of cancer genomics. Cell 173: 305–320. [PMC free article: PMC5916814] [PubMed: 29625049]
    280.
    Bailey M.H. et al. (2018) Comprehensive characterization of cancer driver genes and mutations. Cell 173: 371–385. [PMC free article: PMC6029450] [PubMed: 29625053]
    281.
    Liu T., Yuan X. and Xu D. (2016) Cancer-specific telomerase reverse transcriptase (TERT) promoter mutations: Biological and clinical implications. Genes 7: 38. [PMC free article: PMC4962008] [PubMed: 27438857]
    282.
    Yuan X., Larsson C. and Xu D. (2019) Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: Old actors and new players. Oncogene 38: 6172–6183. [PMC free article: PMC6756069] [PubMed: 31285550]
    283.
    Kumar S. et al. (2020) Passenger mutations in more than 2,500 cancer genomes: Overall molecular functional impact and consequences. Cell 180: 915–927. [PMC free article: PMC7210002] [PubMed: 32084333]
    284.
    Rheinbay E. et al. (2020) Analyses of non-coding somatic drivers in 2,658 cancer whole genomes. Nature 578: 102–111. [PMC free article: PMC7054214] [PubMed: 32025015]
    285.
    Tsimberidou A.M., Fountzilas E., Nikanjam M. and Kurzrock R. (2020) Review of precision cancer medicine: Evolution of the treatment paradigm. Cancer Treatment Reviews 86: 102019. [PMC free article: PMC7272286] [PubMed: 32251926]
    286.
    Malone E.R., Oliva M., Sabatini P.J.B., Stockley T.L. and Siu L.L. (2020) Molecular profiling for precision cancer therapies. Genome Medicine 12: 8. [PMC free article: PMC6961404] [PubMed: 31937368]
    287.
    Waldman A.D., Fritz J.M. and Lenardo M.J. (2020) A guide to cancer immunotherapy: From T cell basic science to clinical practice. Nature Reviews Immunology 20: 651–668. [PMC free article: PMC7238960] [PubMed: 32433532]
    288.
    Esfahani K. et al. (2020) A review of cancer immunotherapy: From the past, to the present, to the future. Current Oncology 27: S87–97. [PMC free article: PMC7194005] [PubMed: 32368178]
    289.
    Blass E. and Ott P.A. (2021) Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nature Reviews Clinical Oncology 18: 215–229. [PMC free article: PMC7816749] [PubMed: 33473220]
    290.
    Johnston J.J. et al. (2012) Secondary variants in individuals undergoing exome sequencing: Screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. American Journal of Human Genetics 91: 97–108. [PMC free article: PMC3397257] [PubMed: 22703879]
    291.
    Grzymski J.J. et al. (2020) Population genetic screening efficiently identifies carriers of autosomal dominant diseases. Nature Medicine 26: 1235–1239. [PubMed: 32719484]
    292.
    Huang K.-L. et al. (2018) Pathogenic germline variants in 10,389 adult cancers. Cell 173: 355–370. [PMC free article: PMC5949147] [PubMed: 29625052]
    293.
    Moscow J.A., Fojo T. and Schilsky R.L. (2018) The evidence framework for precision cancer medicine. Nature Reviews Clinical Oncology 15: 183–192. [PubMed: 29255239]
    294.
    Miga K.H. et al. (2020) Telomere-to-telomere assembly of a complete human X chromosome. Nature 585: 79–84. [PMC free article: PMC7484160] [PubMed: 32663838]
    295.
    Logsdon G.A. et al. (2021) The structure, function and evolution of a complete human chromosome 8. Nature 593: 101–107. [PMC free article: PMC8099727] [PubMed: 33828295]
    296.
    Bergström A. et al. (2020) Insights into human genetic variation and population history from 929 diverse genomes. Science 367: eaay5012. [PMC free article: PMC7115999] [PubMed: 32193295]

    Chapter 12

    1.
    Ruvkun G., Wightman B. and Ha I. (2004) The 20 years it took to recognize the importance of tiny RNAs. Cell 116: S93–6. [PubMed: 15055593]
    2.
    Zamore P.D. and Haley B. (2005) Ribo-gnome: The big world of small RNAs. Science 309: 1519–1524. [PubMed: 16141061]
    3.
    Rich A. and Davies D.R. (1956) A new two-stranded helical structure: Polyadenylic acid and polyuridylic acid. Journal of the American Chemical Society 78: 3548–3549.
    4.
    Isaacs A. and Lindenmann J. (1957) Virus interference. 1. The Interferon. Proceedings of the Royal Society B: Biological Sciences 147: 258–267. [PubMed: 13465720]
    5.
    Pestka S. (2007) The Interferons: 50 years after their discovery, there is much more to learn. Journal of Biological Chemistry 282: 20047–20051. [PubMed: 17502369]
    6.
    Schneider W.M., Chevillotte M.D. and Rice C.M. (2014) Interferon-stimulated genes: A complex web of host defenses. Annual Review of Immunology 32: 513–545. [PMC free article: PMC4313732] [PubMed: 24555472]
    7.
    Schroder K., Hertzog P.J., Ravasi T. and Hume D.A. (2004) Interferon-γ: An overview of signals, mechanisms and functions. Journal of Leukocyte Biology 75: 163–189. [PubMed: 14525967]
    8.
    Lewis U.J., Rickes E.L., Williams D.E., McClelland L. and Brink N.G. (1960) Studies on the antiviral agent Helenine. Purification and evidence for ribonucleoprotein nature. Journal of the American Chemical Society 82: 5178–5182.
    9.
    Tytell A.A., Lampson G.P., Field A.K. and Hilleman M.R. (1967) Inducers of interferon and host resistance. 3. Double-stranded RNA from reovirus type 3 virions (reo 3-RNA). Proceedings of the National Academy of Sciences USA 58: 1719–1722. [PMC free article: PMC223985] [PubMed: 4295834]
    10.
    Lampson G.P., Tytell A.A., Field A.K., Nemes M.M. and Hilleman M.R. (1967) Inducers of interferon and host resistance. I. Double-stranded RNA from extracts of Penicillium funiculosum. Proceedings of the National Academy of Sciences USA 58: 782–789. [PMC free article: PMC335701] [PubMed: 5233474]
    11.
    Field A.K., Lampson G.P., Tytell A.A., Nemes M.M. and Hilleman M.R. (1967) Inducers of interferon and host resistance, IV. Double-stranded replicative form RNA (MS2-Ff-RNA) from E. coli infected with MS2 coliphage. Proceedings of the National Academy of Sciences USA 58: 2102–2108. [PMC free article: PMC223911] [PubMed: 4295588]
    12.
    Hilleman M.R. (1970) Double-stranded RNAs (Poly I:C) in the prevention of viral infections. Archives of Internal Medicine 126: 109–124. [PubMed: 4316618]
    13.
    Ehrenfeld E. and Hunt T. (1971) Double-stranded poliovirus RNA inhibits initiation of protein synthesis by reticulocyte lysates. Proceedings of the National Academy of Sciences USA 68: 1075–1078. [PMC free article: PMC389116] [PubMed: 4325000]
    14.
    Kerr I.M., Brown R.E. and Ball L.A. (1974) Increased sensitivity of cell-free protein synthesis to double-stranded RNA after interferon treatment. Nature 250: 57–59. [PubMed: 4366491]
    15.
    Buck K.W. (1988) From interferon induction to fungal viruses. European Journal of Epidemiology 4: 395–399. [PubMed: 2462507]
    16.
    Banks G.T. et al. (1968) Viruses in fungi and interferon stimulation. Nature 218: 542–545. [PubMed: 4967851]
    17.
    Wingard S.A. (1928) Hosts and symptoms of ring spot, a virus disease of plants. Journal of Agricultural Research 37: 127–154.
    18.
    Hoskins M. (1935) A protective action of neurotropic against viscerotropic Yellow Fever Virus in Macacus Rhesus. American Journal of Tropical Medicine and Hygiene s1–15: 675–680.
    19.
    Kerr I.M., Brown R.E. and Hovanessian A.G. (1977) Nature of inhibitor of cell-free protein synthesis formed in response to interferon and double-stranded RNA. Nature 268: 540–542. [PubMed: 196217]
    20.
    Hovanessian A.G. (1989) The double stranded RNA-activated protein kinase induced by interferon: dsRNA-PK. Journal of Interferon Research 9: 641–647. [PubMed: 2481698]
    21.
    Coleman J., Hirashima A., Inokuchi Y., Green P.J. and Inouye M. (1985) A novel immune system against bacteriophage infection using complementary RNA (micRNA). Nature 315: 601–603. [PubMed: 2409446]
    22.
    Giunta S. and Groppa G. (1985) Interferon and micRNA in cellular defence. Nature 318: 237. [PubMed: 2415823]
    23.
    Takeda K., Kaisho T. and Akira S. (2003) Toll-like receptors. Annual Review of Immunology 21: 335–376. [PubMed: 12524386]
    24.
    Karikó K., Buckstein M., Ni H. and Weissman D. (2005) Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23: 165–175. [PubMed: 16111635]
    25.
    Kawasaki T. and Kawai T. (2014) Toll-like receptor signaling pathways. Frontiers in Immunology 5: 461. [PMC free article: PMC4174766] [PubMed: 25309543]
    26.
    Fitzgerald K.A. and Kagan J.C. (2020) Toll-like receptors and the control of immunity. Cell 180: 1044–1066. [PMC free article: PMC9358771] [PubMed: 32164908]
    27.
    Ward A., Hong W., Favaloro V. and Luo L. (2015) Toll receptors instruct axon and dendrite targeting and participate in synaptic partner matching in a Drosophila olfactory circuit. Neuron 85: 1013–1028. [PMC free article: PMC4351475] [PubMed: 25741726]
    28.
    Foldi I. et al. (2017) Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila. Journal of Cell Biology 216: 1421–1438. [PMC free article: PMC5412559] [PubMed: 28373203]
    29.
    Anthoney N., Foldi I. and Hidalgo A. (2018) Toll and Toll-like receptor signalling in development. Development 145: dev156018. [PubMed: 29695493]
    30.
    Chen C.-Y., Shih Y.-C., Hung Y.-F. and Hsueh Y.-P. (2019) Beyond defense: Regulation of neuronal morphogenesis and brain functions via Toll-like receptors. Journal of Biomedical Science 26: 90. [PMC free article: PMC6827257] [PubMed: 31684953]
    31.
    Karikó K. et al. (2008) Incorporation of pseudouridine Into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular Therapy 16: 1833–1840. [PMC free article: PMC2775451] [PubMed: 18797453]
    32.
    Fire A.Z. (2007) Gene silencing by double-stranded RNA (Nobel lecture). Angewandte Chemie-International Edition 46: 6967–6984. [PubMed: 17722137]
    33.
    Fire A., Albertson D., Harrison S.W. and Moerman D.G. (1991) Production of antisense RNA leads to effective and specific inhibition of gene expression in C. elegans muscle. Development 113: 503–514. [PubMed: 1782862]
    34.
    Guo S. and Kemphues K.J. (1995) par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81: 611–620. [PubMed: 7758115]
    35.
    Cogoni C. and Macino G. (2000) Post-transcriptional gene silencing across kingdoms. Current Opinion in Genetics and Development 10: 638–643. [PubMed: 11088014]
    36.
    Lindbo J.A., Silva-Rosales L., Proebsting W.M. and Dougherty W.G. (1993) Induction of a highly specific antiviral state in transgenic plants: Implications for regulation of gene expression and virus resistance. Plant Cell 5: 1749–1759. [PMC free article: PMC160401] [PubMed: 12271055]
    37.
    Covey S.N., AlKaff N.S., Langara A. and Turner D.S. (1997) Plants combat infection by gene silencing. Nature 385: 781–782.
    38.
    Ratcliff F., Harrison B.D. and Baulcombe D.C. (1997) A similarity between viral defense and gene silencing in plants. Science 276: 1558–1560. [PubMed: 18610513]
    39.
    Ecker J.R. and Davis R.W. (1986) Inhibition of gene expression in plant cells by expression of antisense RNA. Proceedings of the National Academy of Sciences USA 83: 5372–5376. [PMC free article: PMC386288] [PubMed: 16593734]
    40.
    van der Krol A.R. et al. (1988) An anti-sense chalcone synthase gene in transgenic plants inhibits flower pigmentation. Nature 333: 866–869.
    41.
    Jorgensen R.A., Cluster P.D., English J., Que Q. and Napoli C.A. (1996) Chalcone synthase cosuppression phenotypes in petunia flowers: Comparison of sense vs. antisense constructs and single-copy vs. complex T-DNA sequences. Plant Molecular Biology 31: 957–973. [PubMed: 8843939]
    42.
    Scheid O.M. (2019) Illuminating (white and) purple patches. Plant Cell 31: 1208–1209. [PMC free article: PMC6588294] [PubMed: 31036597]
    43.
    Van Blokland R., Vandergeest N., Mol J.N.M. and Kooter J.M. (1994) Transgene-mediated suppression of chalcone synthase expression in petunia-hybrida results from an increase in RNA turnover. Plant Journal 6: 861–877.
    44.
    Napoli C., Lemieux C. and Jorgensen R. (1990) Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 2: 279–289. [PMC free article: PMC159885] [PubMed: 12354959]
    45.
    van der Krol A.R., Mur L.A., Beld M., Mol J.N. and Stuitje A.R. (1990) Flavonoid genes in petunia: Addition of a limited number of gene copies may lead to a suppression of gene expression. Plant Cell 2: 291–299. [PMC free article: PMC159886] [PubMed: 2152117]
    46.
    Romano N. and Macino G. (1992) Quelling: Transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences. Molecular Microbiology 6: 3343–3353. [PubMed: 1484489]
    47.
    Jorgensen R.A., Atkinson R.G., Forster R.L.S. and Lucas W.J. (1998) An RNA-based information superhighway in plants. Science 279: 1486–1487. [PubMed: 9508725]
    48.
    Matzke M.A. and Matzke A. (1995) How and why do plants inactivate homologous (trans)genes? Plant Physiology 107: 679–685. [PMC free article: PMC157182] [PubMed: 12228391]
    49.
    Matzke M.A., Aufsatz W., Kanno T., Mette M.F. and Matzke A.J. (2002) Homology-dependent gene silencing and host defense in plants. Advances in Genetics 46: 235–275. [PubMed: 11931226]
    50.
    Rocheleau C.E. et al. (1997) Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 90: 707–716. [PubMed: 9288750]
    51.
    Pal-Bhadra M., Bhadra U. and Birchler J.A. (1997) Cosuppression in Drosophila: Gene silencing of Alcohol dehydrogenase by white-Adh transgenes is Polycomb dependent. Cell 90: 479–490. [PubMed: 9267028]
    52.
    Pal-Bhadra M., Bhadra U. and Birchler J.A. (1999) Cosuppression of nonhomologous transgenes in Drosophila involves mutually related endogenous sequences. Cell 99: 35–46. [PubMed: 10520992]
    53.
    Abel P.P. et al. (1986) Delay of disease development in transgenic plants that express the tobacco mosaic virus coat protein gene. Science 232: 738–743. [PubMed: 3457472]
    54.
    Rothstein S.J., Dimaio J., Strand M. and Rice D. (1987) Stable and heritable inhibition of the expression of nopaline synthase in tobacco expressing antisense RNA. Proceedings of the National Academy of Sciences USA 84: 8439–8443. [PMC free article: PMC299559] [PubMed: 16593903]
    55.
    Smith C.J.S. et al. (1988) Antisense RNA inhibition of polygalacturonase gene-expression in transgenic tomatoes. Nature 334: 724–726.
    56.
    Herrera-Estrella L., Depicker A., Van Montagu M. and Schell J. (1983) Expression of chimaeric genes transferred into plant cells using a Ti-plasmid-derived vector. Nature 303: 209–213. [PubMed: 1422044]
    57.
    Smith H.A., Swaney S.L., Parks T.D., Wernsman E.A. and Dougherty W.G. (1994) Transgenic plant virus resistance mediated by untranslatable sense RNAs: Expression, regulation, and fate of nonessential RNAs. Plant Cell 6: 1441–1453. [PMC free article: PMC160532] [PubMed: 7994177]
    58.
    Smith C.J. et al. (1990) Expression of a truncated tomato polygalacturonase gene inhibits expression of the endogenous gene in transgenic plants. Molecular and General Genetics 224: 477–481. [PubMed: 2266949]
    59.
    Grierson D., Fray R.G., Hamilton A.J., Smith C.J.S. and Watson C.F. (1991) Does co-suppression of sense genes in transgenic plants involve antisense RNA. Trends in Biotechnology 9: 122–123.
    60.
    Jorgensen R.A., Que Q. and Stam M. (1999) Do unintended antisense transcripts contribute to sense cosuppression in plants? Trends in Genetics 15: 11–12. [PubMed: 10087927]
    61.
    Wassenegger M., Heimes S., Riedel L. and Sänger H.L. (1994) RNA-directed de novo methylation of genomic sequences in plants. Cell 76: 567–576. [PubMed: 8313476]
    62.
    Baulcombe D.C. (1996) RNA as a target and an initiator of post-transcriptional gene silencing in transgenic plants. Plant Molecular Biology 32: 79–88. [PubMed: 8980475]
    63.
    Meyer P. and Saedler H. (1996) Homology-dependent gene silencing in plants. Annual Review of Plant Physiology and Plant Molecular Biology 47: 23–48. [PubMed: 15012281]
    64.
    Stam M., Mol J.N.M. and Kooter J.M. (1997) The silence of genes in transgenic plants. Annals of Botany 79: 3–12.
    65.
    Jones L. et al. (1999) RNA-DNA interactions and DNA methylation in post-transcriptional gene silencing. Plant Cell 11: 2291–2302. [PMC free article: PMC144133] [PubMed: 10590159]
    66.
    Goyon C. and Faugeron G. (1989) Targeted transformation of Ascobolus immersus and de novo methylation of the resulting duplicated DNA sequences. Molecular and Cellular Biology 9: 2818–2827. [PMC free article: PMC362747] [PubMed: 2674671]
    67.
    Assaad F.F., Tucker K.L. and Signer E.R. (1993) Epigenetic repeat-induced gene silencing (RIGS) in Arabidopsis. Plant Molecular Biology 22: 1067–1085. [PubMed: 8400126]
    68.
    Stam M., Viterbo A., Mol J.N.M. and Kooter J.M. (1998) Position-dependent methylation and transcriptional silencing of transgenes in inverted t-dna repeats: Implications for posttranscriptional silencing of homologous host genes in plants. Molecular and Cellular Biology 18: 6165–6177. [PMC free article: PMC109204] [PubMed: 9774634]
    69.
    Mette M.F., Aufsatz W., van Der Winden J., Matzke M.A. and Matzke A.J. (2000) Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO Journal 19: 5194–201. [PMC free article: PMC302106] [PubMed: 11013221]
    70.
    de Carvalho F. et al. (1992) Suppression of beta-1,3-glucanase transgene expression in homozygous plants. EMBO Journal 11: 2595–2602. [PMC free article: PMC556734] [PubMed: 1378394]
    71.
    Sijen T. et al. (2001) Transcriptional and posttranscriptional gene silencing are mechanistically related. Current Biology 11: 436–440. [PubMed: 11301254]
    72.
    Pal-Bhadra M., Bhadra U. and Birchler J.A. (2002) RNAi related mechanisms affect both transcriptional and posttranscriptional transgene silencing in Drosophila. Molecular Cell 9: 315–327. [PubMed: 11864605]
    73.
    Voinnet O. and Baulcombe D.C. (1997) Systemic signalling in gene silencing. Nature 389: 553. [PubMed: 9335491]
    74.
    Cogoni C. et al. (1996) Transgene silencing of the al-1 gene in vegetative cells of Neurospora is mediated by a cytoplasmic effector and does not depend on DNA-DNA interactions or DNA methylation. EMBO Journal 15: 3153–3163. [PMC free article: PMC450258] [PubMed: 8670816]
    75.
    Palauqui J.C., Elmayan T., Pollien J.M. and Vaucheret H. (1997) Systemic acquired silencing: Transgene-specific post-transcriptional silencing is transmitted by grafting from silenced stocks to non-silenced scions. EMBO Journal 16: 4738–4745. [PMC free article: PMC1170100] [PubMed: 9303318]
    76.
    Voinnet O., Vain P., Angell S. and Baulcombe D.C. (1998) Systemic spread of sequence-specific transgene RNA degradation in plants is initiated by localized introduction of ectopic promoterless DNA. Cell 95: 177–187. [PubMed: 9790525]
    77.
    Angell S.M. and Baulcombe D.C. (1997) Consistent gene silencing in transgenic plants expressing a replicating potato virus X RNA. EMBO Journal 16: 3675–3684. [PMC free article: PMC1169991] [PubMed: 9218808]
    78.
    Metzlaff M., O‘Dell M., Cluster P.D. and Flavell R.B. (1997) RNA-mediated RNA degradation and chalcone synthase A silencing in petunia. Cell 88: 845–854. [PubMed: 9118227]
    79.
    Hamilton A.J. and Baulcombe D.C. (1999) A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286: 950–952. [PubMed: 10542148]
    80.
    Barry C.S., Llop-Tous M.I. and Grierson D. (2000) The regulation of 1-aminocyclopropane-1-carboxylic acid synthase gene expression during the transition from system-1 to system-2 ethylene synthesis in tomato. Plant Physiology 123: 979–986. [PMC free article: PMC59060] [PubMed: 10889246]
    81.
    Fire A. et al. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806–811. [PubMed: 9486653]
    82.
    Waterhouse P.M., Graham M.W. and Wang M.B. (1998) Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA. Proceedings of the National Academy of Sciences USA 95: 13959–13964. [PMC free article: PMC24986] [PubMed: 9811908]
    83.
    Ngo H., Tschudi C., Gull K. and Ullu E. (1998) Double-stranded RNA induces mRNA degradation in Trypanosoma brucei. Proceedings of the National Academy of Sciences USA 95: 14687–14692. [PMC free article: PMC24510] [PubMed: 9843950]
    84.
    Kennerdell J.R. and Carthew R.W. (1998) Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95: 1017–1026. [PubMed: 9875855]
    85.
    Tuschl T., Zamore P.D., Lehmann R., Bartel D.P. and Sharp P.A. (1999) Targeted mRNA degradation by double-stranded RNA in vitro. Genes & Development 13: 3191–3197. [PMC free article: PMC317199] [PubMed: 10617568]
    86.
    Kennerdell J.R. and Carthew R.W. (2000) Heritable gene silencing in Drosophila using double-stranded RNA. Nature Biotechnology 18: 896–898. [PubMed: 10932163]
    87.
    Yang D., Lu H. and Erickson J.W. (2000) Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Current Biology 10: 1191–1200. [PubMed: 11050387]
    88.
    Wianny F. and Zernicka-Goetz M. (2000) Specific interference with gene function by double-stranded RNA in early mouse development. Nature Cell Biology 2: 70–75. [PubMed: 10655585]
    89.
    Elbashir S.M. et al. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411: 494–498. [PubMed: 11373684]
    90.
    Caplen N.J., Parrish S., Imani F., Fire A. and Morgan R.A. (2001) Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems. Proceedings of the National Academy of Sciences USA 98: 9742–9747. [PMC free article: PMC55523] [PubMed: 11481446]
    91.
    Grishok A., Tabara H. and Mello C.C. (2000) Genetic requirements for inheritance of RNAi in C. elegans. Science 287: 2494–2497. [PubMed: 10741970]
    92.
    Hammond S.M., Caudy A.A. and Hannon G.J. (2001) Post-transcriptional gene silencing by double-stranded RNA. Nature Reviews Genetics 2: 1110–1119. [PubMed: 11253050]
    93.
    Cogoni C. and Macino G. (1997) Isolation of quelling-defective (qde) mutants impaired in posttranscriptional transgene-induced gene silencing in Neurospora crassa. Proceedings of the National Academy of Sciences USA 94: 10233–10238. [PMC free article: PMC23345] [PubMed: 9294193]
    94.
    Cogoni C. and Macino G. (1999) Gene silencing in Neurospora crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature 399: 166–169. [PubMed: 10335848]
    95.
    Astier-Manifacier S. and Cornuet P. (1971) RNA-dependent RNA polymerase in Chinese cabbage. Biochimica et Biophysica Acta 232: 484–493. [PubMed: 5572618]
    96.
    Schiebel W. et al. (1998) Isolation of an RNA-directed RNA polymerase-specific cDNA clone from tomato. Plant Cell 10: 2087–2101. [PMC free article: PMC143969] [PubMed: 9836747]
    97.
    Schiebel W., Haas B., Marinkovic S., Klanner A. and Sanger H.L. (1993) RNA-directed RNA polymerase from tomato leaves. I. Purification and physical properties. Journal of Biological Chemistry 268: 11851–11857. [PubMed: 7685022]
    98.
    Brennecke J. et al. (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 128: 1089–1103. [PubMed: 17346786]
    99.
    Gunawardane L.S. et al. (2007) A slicer-mediated mechanism for repeat-associated siRNA 5′ end formation in Drosophila. Science 315: 1587–1590. [PubMed: 17322028]
    100.
    Czech B. and Hannon G.J. (2016) One loop to rule them all: The ping-pong cycle and piRNA-guided silencing. Trends in Biochemical Sciences 41: 324–337. [PMC free article: PMC4819955] [PubMed: 26810602]
    101.
    Dalmay T., Hamilton A., Rudd S., Angell S. and Baulcombe D.C. (2000) An RNA-dependent RNA polymerase gene in Arabidopsis is required for posttranscriptional gene silencing mediated by a transgene but not by a virus. Cell 101: 543–553. [PubMed: 10850496]
    102.
    Fagard M., Boutet S., Morel J.B., Bellini C. and Vaucheret H. (2000) AGO1, QDE-2, and RDE-1 are related proteins required for post- transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals. Proceedings of the National Academy of Sciences USA 97: 11650–11654. [PMC free article: PMC17255] [PubMed: 11016954]
    103.
    Shi H. et al. (2000) Genetic interference in Trypanosoma brucei by heritable and inducible double-stranded RNA. RNA 6: 1069–1076. [PMC free article: PMC1369981] [PubMed: 10917601]
    104.
    Sijen T. et al. (2001) On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107: 465–476. [PubMed: 11719187]
    105.
    Zamore P.D. (2002) Ancient pathways programmed by small RNAs. Science 296: 1265–1269. [PubMed: 12016303]
    106.
    Poirier E.Z. et al. (2021) An isoform of Dicer protects mammalian stem cells against multiple RNA viruses. Science 373: 231–236. [PMC free article: PMC7611482] [PubMed: 34244417]
    107.
    Hammond S.M., Bernstein E., Beach D. and Hannon G.J. (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404: 293–296. [PubMed: 10749213]
    108.
    Zamore P.D., Tuschl T., Sharp P.A. and Bartel D.P. (2000) RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101: 25–33. [PubMed: 10778853]
    109.
    Bernstein E., Caudy A.A., Hammond S.M. and Hannon G.J. (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409: 363–366. [PubMed: 11201747]
    110.
    Dougherty W.G. and Parks T.D. (1995) Transgenes and gene suppression: Telling us something new? Current Opinion in Cell Biology 7: 399–405. [PubMed: 7662371]
    111.
    Bohmert K. et al. (1998) AGO1 defines a novel locus of Arabidopsis controlling leaf development. EMBO Journal 17: 170–180. [PMC free article: PMC1170368] [PubMed: 9427751]
    112.
    Farazi T.A., Juranek S.A. and Tuschl T. (2008) The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development 135: 1201–1214. [PubMed: 18287206]
    113.
    Elbashir S.M., Lendeckel W. and Tuschl T. (2001) RNA interference is mediated by 21 and 22 nt RNAs. Genes & Development 15: 188–200. [PMC free article: PMC312613] [PubMed: 11157775]
    114.
    Hall T.M. (2005) Structure and function of argonaute proteins. Structure 13: 1403–1408. [PubMed: 16216572]
    115.
    Peters L. and Meister G. (2007) Argonaute proteins: Mediators of RNA silencing. Molecular Cell 26: 611–623. [PubMed: 17560368]
    116.
    Meins Jr. F., Si-Ammour A. and Blevins T. (2005) RNA silencing systems and their relevance to plant development. Annual Review of Cell and Developmental Biology 21: 297–318. [PubMed: 16212497]
    117.
    Fei Q., Xia R. and Meyers B.C. (2013) Phased, secondary, small interfering RNAs in posttranscriptional regulatory networks. Plant Cell 25: 2400–2415. [PMC free article: PMC3753373] [PubMed: 23881411]
    118.
    Lee C.H. and Carroll B.J. (2018) Evolution and diversification of small RNA pathways in flowering plants. Plant and Cell Physiology 59: 2169–2187. [PubMed: 30169685]
    119.
    Meister G. (2013) Argonaute proteins: Functional insights and emerging roles. Nature Reviews Genetics 14: 447–459. [PubMed: 23732335]
    120.
    Sashital D.G. (2017) Prokaryotic Argonaute uses an all-in-one mechanism to provide host defense. Molecular Cell 65: 957–958. [PubMed: 28306508]
    121.
    Olovnikov I., Chan K., Sachidanandam R., Newman D.K. and Aravin A.A. (2013) Bacterial Argonaute samples the transcriptome to identify foreign DNA. Molecular Cell 51: 594–605. [PMC free article: PMC3809076] [PubMed: 24034694]
    122.
    Swarts D.C. et al. (2014) DNA-guided DNA interference by a prokaryotic Argonaute. Nature 507: 258–261. [PMC free article: PMC4697943] [PubMed: 24531762]
    123.
    Swarts D.C. et al. (2017) Autonomous generation and loading of DNA guides by bacterial Argonaute. Molecular Cell 65: 985–998. [PMC free article: PMC5779613] [PubMed: 28262506]
    124.
    Kaya E. et al. (2016) A bacterial Argonaute with noncanonical guide RNA specificity. Proceedings of the National Academy of Sciences USA 113: 4057–4062. [PMC free article: PMC4839417] [PubMed: 27035975]
    125.
    Drinnenberg I.A., Fink G.R. and Bartel D.P. (2011) Compatibility with killer explains the rise of RNAi-deficient fungi. Science 333: 1592. [PMC free article: PMC3790311] [PubMed: 21921191]
    126.
    Becker B. and Schmitt M.J. (2017) Yeast killer toxin K28: Biology and unique strategy of host cell intoxication and killing. Toxins 9: 333. [PMC free article: PMC5666379] [PubMed: 29053588]
    127.
    Wassarman K.M., Repoila F., Rosenow C., Storz G. and Gottesman S. (2001) Identification of novel small RNAs using comparative genomics and microarrays. Genes & Development 15: 1637–1651. [PMC free article: PMC312727] [PubMed: 11445539]
    128.
    Møller T. et al. (2002) Hfq: A bacterial Sm-like protein that mediates RNA-RNA interaction. Molecular Cell 9: 23–30. [PubMed: 11804583]
    129.
    Zhang A., Wassarman K.M., Ortega J., Steven A.C. and Storz G. (2002) The Sm-like Hfq protein increases OxyS RNA interaction with target mRNAs. Molecular Cell 9: 11–22. [PubMed: 11804582]
    130.
    Schumacher M.A., Pearson R.F., Møller T., Valentin-Hansen P. and Brennan R.G. (2002) Structures of the pleiotropic translational regulator Hfq and an Hfq-RNA complex: A bacterial Sm-like protein. EMBO Journal 21: 3546–3556. [PMC free article: PMC126077] [PubMed: 12093755]
    131.
    Geissmann T.A. and Touati D. (2004) Hfq, a new chaperoning role: Binding to messenger RNA determines access for small RNA regulator. EMBO Journal 23: 396–405. [PMC free article: PMC1271764] [PubMed: 14739933]
    132.
    Lenz D.H. et al. (2004) The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118: 69–82. [PubMed: 15242645]
    133.
    Jose A.M. and Hunter C.P. (2007) Transport of sequence-specific RNA interference information between cells. Annual Review of Genetics 41: 305–330. [PMC free article: PMC7377521] [PubMed: 17645412]
    134.
    Winston W.M., Molodowitch C. and Hunter C.P. (2002) Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 295: 2456–2459. [PubMed: 11834782]
    135.
    Winston W.M., Sutherlin M., Wright A.J., Feinberg E.H. and Hunter C.P. (2007) Caenorhabditis elegans SID-2 is required for environmental RNA interference. Proceedings of the National Academy of Sciences USA 104: 10565–10570. [PMC free article: PMC1965553] [PubMed: 17563372]
    136.
    Nguyen T.A. et al. (2017) SIDT2 transports extracellular dsRNA into the cytoplasm for innate immune recognition. Immunity 47: 498–509. [PMC free article: PMC5679266] [PubMed: 28916264]
    137.
    Nguyen T.A. et al. (2019) SIDT1 localizes to endolysosomes and mediates double-stranded RNA transport into the cytoplasm. Journal of Immunology 202: 3483–3492. [PubMed: 31061008]
    138.
    Molnar A. et al. (2010) Small silencing RNAs in plants are mobile and direct epigenetic modification in recipient cells. Science 328: 872–875. [PubMed: 20413459]
    139.
    Dickson E. and Robertson H.D. (1976) Potential regulatory roles for RNA in cellular development. Cancer Research 36: 3387–3393. [PubMed: 975098]
    140.
    Benner S.A. (1988) Extracellular ‘communicator RNA’. FEBS Letters 233: 225–228. [PubMed: 2454845]
    141.
    Valadi H. et al. (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology 9: 654–659. [PubMed: 17486113]
    142.
    Dinger M.E., Mercer T.R. and Mattick J.S. (2008) RNAs as extracellular signaling molecules. Journal of Molecular Endocrinology 40: 151–159. [PubMed: 18372404]
    143.
    Wahlgren J. et al. (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Research 40: e130. [PMC free article: PMC3458529] [PubMed: 22618874]
    144.
    O’Brien K., Breyne K., Ughetto S., Laurent L.C. and Breakefield X.O. (2020) RNA delivery by extracellular vesicles in mammalian cells and its applications. Nature Reviews Molecular Cell Biology 21: 585–606. [PMC free article: PMC7249041] [PubMed: 32457507]
    145.
    Mittelbrunn M. et al. (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nature Communications 2: 282. [PMC free article: PMC3104548] [PubMed: 21505438]
    146.
    Montecalvo A. et al. (2012) Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119: 756–766. [PMC free article: PMC3265200] [PubMed: 22031862]
    147.
    Okoye I.S. et al. (2014) MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells. Immunity 41: 89–103. [PMC free article: PMC4104030] [PubMed: 25035954]
    148.
    Thomou T. et al. (2017) Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature 542: 450–455. [PMC free article: PMC5330251] [PubMed: 28199304]
    149.
    Turchinovich A., Drapkina O. and Tonevitsky A. (2019) Transcriptome of extracellular vesicles: State-of-the-art. Frontiers in Immunology 10: 202. [PMC free article: PMC6404625] [PubMed: 30873152]
    150.
    Reggiardo R.E. et al. (2020) Epigenomic reprogramming of repetitive noncoding RNAs and IFN-stimulated genes by mutant KRAS. bioRxiv: 2020.11.04.367771.
    151.
    Zhang Y. et al. (2017) Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature 548: 52–57. [PMC free article: PMC5999038] [PubMed: 28746310]
    152.
    Skog J. et al. (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nature Cell Biology 10: 1470–1476. [PMC free article: PMC3423894] [PubMed: 19011622]
    153.
    Azmi A.S., Bao B. and Sarkar F.H. (2013) Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review. Cancer and Metastasis Reviews 32: 623–642. [PMC free article: PMC3843988] [PubMed: 23709120]
    154.
    Rana S., Malinowska K. and Zöller M. (2013) Exosomal tumor microRNA modulates premetastatic organ cells. Neoplasia 15: 281–295. [PMC free article: PMC3593151] [PubMed: 23479506]
    155.
    Albanese M. et al. (2021) MicroRNAs are minor constituents of extracellular vesicles that are rarely delivered to target cells. PLOS Genetics 17: e1009951. [PMC free article: PMC8675925] [PubMed: 34871319]
    156.
    Garcia-Martin R. et al. (2022) MicroRNA sequence codes for small extracellular vesicle release and cellular retention. Nature 601: 446–451. [PMC free article: PMC9035265] [PubMed: 34937935]
    157.
    Mette M.F., van der Winden J., Matzke M.A. and Matzke A.J.M. (1999) Production of aberrant promoter transcripts contributes to methylation and silencing of unlinked homologous promoters in trans. EMBO Journal 18: 241–248. [PMC free article: PMC1171118] [PubMed: 9878066]
    158.
    Morel J., Mourrain P., Beclin C. and Vaucheret H. (2000) DNA methylation and chromatin structure affect transcriptional and post-transcriptional transgene silencing in Arabidopsis. Current Biology 10: 1591–1594. [PubMed: 11137011]
    159.
    Matzke M.A. and Mosher R.A. (2014) RNA-directed DNA methylation: An epigenetic pathway of increasing complexity. Nature Reviews Genetics 15: 394–408. [PubMed: 24805120]
    160.
    Erdmann R.M. and Picard C.L. (2020) RNA-directed DNA methylation. PLOS Genetics 16: e1009034. [PMC free article: PMC7544125] [PubMed: 33031395]
    161.
    Wassenegger M. (2000) RNA-directed DNA methylation. Plant Molecular Biology 43: 203–220. [PubMed: 10999405]
    162.
    Pal-Bhadra M. et al. (2004) Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303: 669–672. [PubMed: 14752161]
    163.
    Fukagawa T. et al. (2004) Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nature Cell Biology 6: 784–791. [PubMed: 15247924]
    164.
    Morris K.V., Chan S.W., Jacobsen S.E. and Looney D.J. (2004) Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305: 1289–1292. [PubMed: 15297624]
    165.
    Castel S.E. and Martienssen R.A. (2013) RNA interference in the nucleus: Roles for small RNAs in transcription, epigenetics and beyond. Nature Reviews Genetics 14: 100–112. [PMC free article: PMC4205957] [PubMed: 23329111]
    166.
    Janowski B.A. et al. (2006) Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nature Structural & Molecular Biology 13: 787–792. [PubMed: 16936728]
    167.
    Kim D.H., Villeneuve L.M., Morris K.V. and Rossi J.J. (2006) Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nature Structural & Molecular Biology 13: 793–797. [PubMed: 16936726]
    168.
    Vagin V.V. et al. (2006) A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313: 320–324. [PubMed: 16809489]
    169.
    Gutbrod M.J. and Martienssen R.A. (2020) Conserved chromosomal functions of RNA interference. Nature Reviews Genetics 21: 311–331. [PMC free article: PMC9478574] [PubMed: 32051563]
    170.
    Volpe T.A. et al. (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297: 1833–1837. [PubMed: 12193640]
    171.
    Hall I.M. et al. (2002) Establishment and maintenance of a heterochromatin domain. Science 297: 2232–2237. [PubMed: 12215653]
    172.
    Lippman Z. et al. (2004) Role of transposable elements in heterochromatin and epigenetic control. Nature 430: 471–476. [PubMed: 15269773]
    173.
    Lippman Z. and Martienssen R. (2004) The role of RNA interference in heterochromatic silencing. Nature 431: 364–370. [PubMed: 15372044]
    174.
    Verdel A. et al. (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303: 672–676. [PMC free article: PMC3244756] [PubMed: 14704433]
    175.
    Martienssen R.A., Zaratiegui M. and Goto D.B. (2005) RNA interference and heterochromatin in the fission yeast Schizosaccharomyces pombe. Trends in Genetics 21: 450–456. [PubMed: 15979194]
    176.
    Buhler M., Verdel A. and Moazed D. (2006) Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. Cell 125: 873–886. [PubMed: 16751098]
    177.
    Buhler M., Haas W., Gygi S.P. and Moazed D. (2007) RNAi-dependent and -independent RNA turnover mechanisms contribute to heterochromatic gene silencing. Cell 129: 707–721. [PubMed: 17512405]
    178.
    Buhler M. and Moazed D. (2007) Transcription and RNAi in heterochromatic gene silencing. Nature Structural & Molecular Biology 14: 1041–1048. [PubMed: 17984966]
    179.
    Slotkin R.K. and Martienssen R. (2007) Transposable elements and the epigenetic regulation of the genome. Nature Reviews Genetics 8: 272–285. [PubMed: 17363976]
    180.
    Bayne E.H. et al. (2008) Splicing factors facilitate RNAi-directed silencing in fission yeast. Science 322: 602. [PMC free article: PMC2585287] [PubMed: 18948543]
    181.
    Shimada Y., Mohn F. and Bühler M. (2016) The RNA-induced transcriptional silencing complex targets chromatin exclusively via interacting with nascent transcripts. Genes & Development 30: 2571–2580. [PMC free article: PMC5204350] [PubMed: 27941123]
    182.
    Reinhart B.J. and Bartel D.P. (2002) Small RNAs correspond to centromere heterochromatic repeats. Science 297: 1831. [PubMed: 12193644]
    183.
    Volpe T. et al. (2003) RNA interference is required for normal centromere function in fission yeast. Chromosome Research 11: 137–146. [PubMed: 12733640]
    184.
    Hall I.M., Noma K. and Grewal S.I. (2003) RNA interference machinery regulates chromosome dynamics during mitosis and meiosis in fission yeast. Proceedings of the National Academy of Sciences USA 100: 193–198. [PMC free article: PMC140924] [PubMed: 12509501]
    185.
    Kanellopoulou C. et al. (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes & Development 19: 489–501. [PMC free article: PMC548949] [PubMed: 15713842]
    186.
    Schramke V. and Allshire R. (2003) Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science 301: 1069–1074. [PubMed: 12869699]
    187.
    Mochizuki K., Fine N.A., Fujisawa T. and Gorovsky M.A. (2002) Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in Tetrahymena. Cell 110: 689–699. [PubMed: 12297043]
    188.
    Mochizuki K. and Gorovsky M.A. (2004) Small RNAs in genome rearrangement in Tetrahymena. Current Opinion in Genetics and Development 14: 181–187. [PubMed: 15196465]
    189.
    Nowacki M. et al. (2007) RNA-mediated epigenetic programming of a genome-rearrangement pathway. Nature 451: 153–158. [PMC free article: PMC2647009] [PubMed: 18046331]
    190.
    Nowacki M., Shetty K. and Landweber L.F. (2011) RNA-mediated epigenetic programming of genome rearrangements. Annual Review of Genomics and Human Genetics 12: 367–389. [PMC free article: PMC3518427] [PubMed: 21801022]
    191.
    Swiezewski S. et al. (2007) Small RNA-mediated chromatin silencing directed to the 3′ region of the Arabidopsis gene encoding the developmental regulator, FLC. Proceedings of the National Academy of Sciences USA 104: 3633–3638. [PMC free article: PMC1805594] [PubMed: 17360694]
    192.
    Hu H. and Gatti R.A. (2011) MicroRNAs: New players in the DNA damage response. Journal of Molecular Cell Biology 3: 151–158. [PMC free article: PMC3104011] [PubMed: 21183529]
    193.
    Bhattacharjee S., Roche B. and Martienssen R.A. (2019) RNA-induced initiation of transcriptional silencing (RITS) complex structure and function. RNA Biology 16: 1133–1146. [PMC free article: PMC6693537] [PubMed: 31213126]
    194.
    Collins J., Saari B. and Anderson P. (1987) Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans. Nature 328: 726–728. [PubMed: 3039378]
    195.
    Tabara H. et al. (1999) The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99: 123–132. [PubMed: 10535731]
    196.
    Vastenhouw N.L. and Plasterk R.H.A. (2004) RNAi protects the Caenorhabditis elegans germline against transposition. Trends in Genetics 20: 314–319. [PubMed: 15219396]
    197.
    Yang N. and Kazazian H.H. (2006) L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells. Nature Structural & Molecular Biology 13: 763–771. [PubMed: 16936727]
    198.
    Ghildiyal M. et al. (2008) Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320: 1077–1081. [PMC free article: PMC2953241] [PubMed: 18403677]
    199.
    Bernstein E. et al. (2003) Dicer is essential for mouse development. Nature Genetics 35: 215–217. [PubMed: 14528307]
    200.
    Schuettengruber B., Chourrout D., Vervoort M., Leblanc B. and Cavalli G. (2007) Genome regulation by polycomb and trithorax proteins. Cell 128: 735–745. [PubMed: 17320510]
    201.
    Onodera Y. et al. (2005) Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation. Cell 120: 613–622. [PubMed: 15766525]
    202.
    Pontier D. et al. (2005) Reinforcement of silencing at transposons and highly repeated sequences requires the concerted action of two distinct RNA polymerases IV in Arabidopsis. Genes & Development 19: 2030–2040. [PMC free article: PMC1199573] [PubMed: 16140984]
    203.
    Wierzbicki A.T., Haag J.R. and Pikaard C.S. (2008) Noncoding transcription by RNA polymerase Pol IVb/Pol V mediates transcriptional silencing of overlapping and adjacent genes. Cell 135: 635–648. [PMC free article: PMC2602798] [PubMed: 19013275]
    204.
    Matzke M., Kanno T., Daxinger L., Huettel B. and Matzke A. (2009) RNA-mediated chromatin-based silencing in plants. Current Opinion in Cell Biology 21: 367–376. [PubMed: 19243928]
    205.
    Law J.A. and Jacobsen S.E. (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nature Reviews Genetics 11: 204–220. [PMC free article: PMC3034103] [PubMed: 20142834]
    206.
    Carbonell A. and Carrington J.C. (2015) Antiviral roles of plant ARGONAUTES. Current Opinion in Plant Biology 27: 111–117. [PMC free article: PMC4618181] [PubMed: 26190744]
    207.
    Rymen B., Ferrafiat L. and Blevins T. (2020) Non-coding RNA polymerases that silence transposable elements and reprogram gene expression in plants. Transcription 11: 172–191. [PMC free article: PMC7714444] [PubMed: 33180661]
    208.
    Rechavi O., Minevich G. and Hobert O. (2011) Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell 147: 1248–1256. [PMC free article: PMC3250924] [PubMed: 22119442]
    209.
    Ashe A. et al. (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150: 88–99. [PMC free article: PMC3464430] [PubMed: 22738725]
    210.
    Duempelmann L., Skribbe M. and Bühler M. (2020) Small RNAs in the transgenerational inheritance of epigenetic information. Trends in Genetics 36: 203–214. [PubMed: 31952840]
    211.
    Shukla A. et al. (2020) poly(UG)-tailed RNAs in genome protection and epigenetic inheritance. Nature 582: 283–288. [PMC free article: PMC8396162] [PubMed: 32499657]
    212.
    Burton N.O., Burkhart K.B. and Kennedy S. (2011) Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans. Proceedings of the National Academy of Sciences USA 108: 19683–19688. [PMC free article: PMC3241819] [PubMed: 22106253]
    213.
    Kiani J. et al. (2013) RNA–mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2. PLOS Genetics 9: e1003498. [PMC free article: PMC3662642] [PubMed: 23717211]
    214.
    Wheway G. et al. (2015) An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nature Cell Biology 17: 1074–1087. [PMC free article: PMC4536769] [PubMed: 26167768]
    215.
    Kok K.-H., Lei T. and Jin D.-Y. (2009) siRNA and shRNA screens advance key understanding of host factors required for HIV-1 replication. Retrovirology 6: 78. [PMC free article: PMC2743632] [PubMed: 19712452]
    216.
    Mendes-Pereira A.M. et al. (2012) Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen. Proceedings of the National Academy of Sciences USA 109: 2730–2735. [PMC free article: PMC3286962] [PubMed: 21482774]
    217.
    Setten R.L., Rossi J.J. and Han S.-P. (2019) The current state and future directions of RNAi-based therapeutics. Nature Reviews Drug Discovery 18: 421–446. [PubMed: 30846871]
    218.
    Lykken E.A., Shyng C., Edwards R.J., Rozenberg A. and Gray S.J. (2018) Recent progress and considerations for AAV gene therapies targeting the central nervous system. Journal of Neurodevelopmental Disorders 10: 16. [PMC free article: PMC5960126] [PubMed: 29776328]
    219.
    Lorenzer C., Dirin M., Winkler A.-M., Baumann V. and Winkler J. (2015) Going beyond the liver: Progress and challenges of targeted delivery of siRNA therapeutics. Journal of Controlled Release 203: 1–15. [PubMed: 25660205]
    220.
    Daya S. and Berns K.I. (2008) Gene therapy using adeno-associated virus vectors. Clinical Microbiology Reviews 21: 583–593. [PMC free article: PMC2570152] [PubMed: 18854481]
    221.
    Lundstrom K. (2018) Viral vectors in gene therapy. Diseases 6: 42. [PMC free article: PMC6023384] [PubMed: 29883422]
    222.
    Kaczmarek J.C., Kowalski P.S. and Anderson D.G. (2017) Advances in the delivery of RNA therapeutics: From concept to clinical reality. Genome Medicine 9: 60. [PMC free article: PMC5485616] [PubMed: 28655327]
    223.
    Tatiparti K., Sau S., Kashaw S.K. and Iyer A.K. (2017) siRNA delivery strategies: A comprehensive review of recent developments. Nanomaterials 7: 77. [PMC free article: PMC5408169] [PubMed: 28379201]
    224.
    Dong Y., Siegwart D.J. and Anderson D.G. (2019) Strategies, design, and chemistry in siRNA delivery systems. Advanced Drug Delivery Reviews 144: 133–147. [PMC free article: PMC6745264] [PubMed: 31102606]
    225.
    Paunovska K., Loughrey D. and Dahlman J.E. (2022) Drug delivery systems for RNA therapeutics. Nature Reviews Genetics. epub ahead of print: https://www​.nature.com​/articles/s41576-021-00439-4. [PMC free article: PMC8724758] [PubMed: 34983972]
    226.
    Guo Q., Liu Q., Smith N.A., Liang G. and Wang M.-B. (2016) RNA silencing in plants: Mechanisms, technologies and applications in horticultural crops. Current Genomics 17: 476–489. [PMC free article: PMC5108043] [PubMed: 28217004]
    227.
    Dalakouras A. et al. (2020) Genetically modified organism-free RNA Interference: Exogenous application of RNA molecules in plants. Plant Physiology 182: 38–50. [PMC free article: PMC6945881] [PubMed: 31285292]
    228.
    Naso M.F., Tomkowicz B., Perry 3rd W.L., and Strohl W.R. (2017) Adeno-associated virus (AAV) as a vector for gene therapy. BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy 31: 317–334. [PMC free article: PMC5548848] [PubMed: 28669112]
    229.
    Goswami R. et al. (2019) Gene therapy leaves a vicious cycle. Frontiers in Oncology 9: 297. [PMC free article: PMC6491712] [PubMed: 31069169]
    230.
    Wilton S.D. et al. (2007) Antisense oligonucleotide-induced exon skipping across the human Dystrophin gene transcript. Molecular Therapy 15: 1288–1296. [PubMed: 17285139]
    231.
    Dolgin E. (2019) News Feature: Gene therapy successes point to better therapies. Proceedings of the National Academy of Sciences USA 116: 23866–23870. [PMC free article: PMC6883820] [PubMed: 31772140]
    232.
    Nguyen Q. and Yokota T. (2019) Antisense oligonucleotides for the treatment of cardiomyopathy in Duchenne muscular dystrophy. American Journal of Translational Research 11: 1202–1218. [PMC free article: PMC6456507] [PubMed: 30972156]
    233.
    Russell S. et al. (2017) Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: A randomised, controlled, open-label, phase 3 trial. Lancet 390: 849 –60. [PMC free article: PMC5726391] [PubMed: 28712537]
    234.
    Lee R.C., Feinbaum R.L. and Ambros V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843–854. [PubMed: 8252621]
    235.
    Reinhart B.J. et al. (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403: 901–906. [PubMed: 10706289]
    236.
    Pasquinelli A.E. et al. (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408: 86–89. [PubMed: 11081512]
    237.
    Lagos-Quintana M., Rauhut R., Lendeckel W. and Tuschl T. (2001) Identification of novel genes coding for small expressed RNAs. Science 294: 853–858. [PubMed: 11679670]
    238.
    Slack F.J. et al. (2000) The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Molecular Cell 5: 659–669. [PubMed: 10882102]
    239.
    Grishok A. et al. (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106: 23–34. [PubMed: 11461699]
    240.
    Ambros V. (2008) The evolution of our thinking about microRNAs. Nature Medicine 14: 1036–1040. [PubMed: 18841144]
    241.
    Lau N.C., Lim L.P., Weinstein E.G. and Bartel D.P. (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294: 858–862. [PubMed: 11679671]
    242.
    Lee R.C. and Ambros V. (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294: 862–864. [PubMed: 11679672]
    243.
    Grad Y. et al. (2003) Computational and experimental identification of C. elegans microRNAs. Molecular Cell 11: 1253–1263. [PubMed: 12769849]
    244.
    Lagos-Quintana M. et al. (2002) Identification of tissue-specific microRNAs from mouse. Current Biology 12: 735–739. [PubMed: 12007417]
    245.
    Brennecke J. and Cohen S.M. (2003) Towards a complete description of the microRNA complement of animal genomes. Genome Biology 4: 228. [PMC free article: PMC193649] [PubMed: 12952528]
    246.
    Lagos-Quintana M., Rauhut R., Meyer J., Borkhardt A. and Tuschl T. (2003) New microRNAs from mouse and human. RNA 9: 175–179. [PMC free article: PMC1370382] [PubMed: 12554859]
    247.
    Bentwich I. et al. (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nature Genetics 37: 766–770. [PubMed: 15965474]
    248.
    Berezikov E. et al. (2006) Diversity of microRNAs in human and chimpanzee brain. Nature Genetics 38: 1375–1377. [PubMed: 17072315]
    249.
    Berezikov E. et al. (2006) Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis. Genome Research 16: 1289–1298. [PMC free article: PMC1581438] [PubMed: 16954537]
    250.
    Pasquinelli A.E. (2002) MicroRNAs: Deviants no longer. Trends in Genetics 18: 171–173. [PubMed: 11932009]
    251.
    Ruvkun G. (2001) Glimpses of a tiny RNA world. Science 294: 797–799. [PubMed: 11679654]
    252.
    Clurman B.E. and Hayward W.S. (1989) Multiple proto-oncogene activations in avian leukosis virus-induced lymphomas: Evidence for stage-specific events. Molecular and Cellular Biology 9: 2657–2664. [PMC free article: PMC362338] [PubMed: 2548084]
    253.
    Tam W., Ben-Yehuda D. and Hayward W.S. (1997) bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its noncoding RNA. Molecular and Cellular Biology 17: 1490–1502. [PMC free article: PMC231875] [PubMed: 9032277]
    254.
    Eis P.S. et al. (2005) Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proceedings of the National Academy of Sciences USA 102: 3627–3632. [PMC free article: PMC552785] [PubMed: 15738415]
    255.
    Nguyen L.X.T. et al. (2021) Cytoplasmic DROSHA and non-canonical mechanisms of MiR-155 biogenesis in FLT3-ITD acute myeloid leukemia. Leukemia 35: 2285–2298. [PMC free article: PMC8973317] [PubMed: 33589748]
    256.
    Cai X. and Cullen B.R. (2007) The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA 13: 313–316. [PMC free article: PMC1800509] [PubMed: 17237358]
    257.
    Keniry A. et al. (2012) The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nature Cell Biology 14: 659–665. [PMC free article: PMC3389517] [PubMed: 22684254]
    258.
    Du Q. et al. (2019) MIR205HG Is a long noncoding RNA that regulates growth hormone and prolactin production in the anterior pituitary. Developmental Cell 49: 618–631. [PMC free article: PMC9131289] [PubMed: 30982661]
    259.
    Llave C., Kasschau K.D., Rector M.A. and Carrington J.C. (2002) Endogenous and silencing-associated small RNAs in plants. Plant Cell 14: 1605–1619. [PMC free article: PMC150710] [PubMed: 12119378]
    260.
    Rodriguez A., Griffiths-Jones S., Ashurst J.L. and Bradley A. (2004) Identification of mammalian microRNA host genes and transcription units. Genome Research 14: 1902–1910. [PMC free article: PMC524413] [PubMed: 15364901]
    261.
    Lee Y. et al. (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO Journal 23: 4051–4060. [PMC free article: PMC524334] [PubMed: 15372072]
    262.
    Borchert G.M., Lanier W. and Davidson B.L. (2006) RNA polymerase III transcribes human microRNAs. Nature Structural & Molecular Biology 13: 1097–1101. [PubMed: 17099701]
    263.
    Kim Y.K. and Kim V.N. (2007) Processing of intronic microRNAs. EMBO Journal 26: 775–783. [PMC free article: PMC1794378] [PubMed: 17255951]
    264.
    Dieci G., Fiorino G., Castelnuovo M., Teichmann M. and Pagano A. (2007) The expanding RNA polymerase III transcriptome. Trends in Genetics 23: 614–622. [PubMed: 17977614]
    265.
    Babiarz J.E., Ruby J.G., Wang Y., Bartel D.P. and Blelloch R. (2008) Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes & Development 22: 2773–2785. [PMC free article: PMC2569885] [PubMed: 18923076]
    266.
    Lee Y. et al. (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425: 415–419. [PubMed: 14508493]
    267.
    Han J. et al. (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes & Development 18: 3016–3027. [PMC free article: PMC535913] [PubMed: 15574589]
    268.
    Denli A.M., Tops B.B.J., Plasterk R.H.A., Ketting R.F. and Hannon G.J. (2004) Processing of primary microRNAs by the Microprocessor complex. Nature 432: 231–235. [PubMed: 15531879]
    269.
    Gregory R.I. et al. (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432: 235–240. [PubMed: 15531877]
    270.
    Luhur A., Chawla G., Wu Y.-C., Li J. and Sokol N.S. (2014) Drosha-independent DGCR8/Pasha pathway regulates neuronal morphogenesis. Proceedings of the National Academy of Sciences USA 111: 1421–1426. [PMC free article: PMC3910640] [PubMed: 24474768]
    271.
    Ruby J.G., Jan C.H. and Bartel D.P. (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448: 83–86. [PMC free article: PMC2475599] [PubMed: 17589500]
    272.
    Okamura K., Hagen J.W., Duan H., Tyler D.M. and Lai E.C. (2007) The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 130: 89–100. [PMC free article: PMC2729315] [PubMed: 17599402]
    273.
    Berezikov E., Chung W.J., Willis J., Cuppen E. and Lai E.C. (2007) Mammalian mirtron genes. Molecular Cell 28: 328–336. [PMC free article: PMC2763384] [PubMed: 17964270]
    274.
    Carrington J.C. and Ambros V. (2003) Role of microRNAs in plant and animal development. Science 301: 336–338. [PubMed: 12869753]
    275.
    Jinek M. and Doudna J.A. (2009) A three-dimensional view of the molecular machinery of RNA interference. Nature 457: 405–412. [PubMed: 19158786]
    276.
    Wilson R.C. and Doudna J.A. (2013) Molecular mechanisms of RNA interference. Annual Review of Biophysics 42: 217–239. [PMC free article: PMC5895182] [PubMed: 23654304]
    277.
    Houbaviy H.B., Murray M.F. and Sharp P.A. (2003) Embryonic stem cell-specific microRNAs. Developmental Cell 5: 351–358. [PubMed: 12919684]
    278.
    Suh M.-R. et al. (2004) Human embryonic stem cells express a unique set of microRNAs. Developmental Biology 270: 488–498. [PubMed: 15183728]
    279.
    Wheeler G., Ntounia-Fousara S., Granda B., Rathjen T. and Dalmay T. (2006) Identification of new central nervous system specific mouse microRNAs. FEBS Letters 580: 2195–2200. [PubMed: 16566924]
    280.
    Xu S., Witmer P.D., Lumayag S., Kovacs B. and Valle D. (2007) MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. Journal of Biological Chemistry 282: 25053–25066. [PubMed: 17597072]
    281.
    Axtell M.J. and Bartel D.P. (2005) Antiquity of microRNAs and their targets in land plants. Plant Cell 17: 1658–1673. [PMC free article: PMC1143068] [PubMed: 15849273]
    282.
    Peterson K.J., Dietrich M.R. and McPeek M.A. (2009) MicroRNAs and metazoan macroevolution: Insights into canalization, complexity, and the Cambrian explosion. BioEssays 31: 736–747. [PubMed: 19472371]
    283.
    Hake S. (2003) MicroRNAs: A role in plant development. Current Biology 13: R851–2. [PubMed: 14588265]
    284.
    DeVeale B., Swindlehurst-Chan J. and Blelloch R. (2021) The roles of microRNAs in mouse development. Nature Reviews Genetics 22: 307–323. [PubMed: 33452500]
    285.
    Chakraborty M. et al. (2020) MicroRNAs organize intrinsic variation into stem cell states. Proceedings of the National Academy of Sciences USA 117: 6942–6950. [PMC free article: PMC7104302] [PubMed: 32139605]
    286.
    Brennecke J., Hipfner D.R., Stark A., Russell R.B. and Cohen S.M. (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113: 25–36. [PubMed: 12679032]
    287.
    Gregory P.A. et al. (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology 10: 593–601. [PubMed: 18376396]
    288.
    Giraldez A.J. et al. (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science 308: 833–838. [PubMed: 15774722]
    289.
    Chen C.Z., Li L., Lodish H.F. and Bartel D.P. (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303: 83–86. [PubMed: 14657504]
    290.
    Johnston R.J. and Hobert O. (2003) A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426: 845–849. [PubMed: 14685240]
    291.
    Schratt G.M. et al. (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439: 283–289. [PubMed: 16421561]
    292.
    O‘Rourke J.R. et al. (2007) Essential role for Dicer during skeletal muscle development. Developmental Biology 311: 359–368. [PMC free article: PMC2753295] [PubMed: 17936265]
    293.
    Baehrecke E.H. (2003) miRNAs: Micro managers of programmed cell death. Current Biology 13: R473–5. [PubMed: 12814564]
    294.
    Taganov K.D., Boldin M.P., Chang K.-J. and Baltimore D. (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proceedings of the National Academy of Sciences USA 103: 12481–12486. [PMC free article: PMC1567904] [PubMed: 16885212]
    295.
    Boehm M. and Slack F.J. (2006) MicroRNA control of lifespan and metabolism. Cell Cycle 5: 837–840. [PubMed: 16627994]
    296.
    Palatnik J.F. et al. (2003) Control of leaf morphogenesis by microRNAs. Nature 425: 257–263. [PubMed: 12931144]
    297.
    Mallory A.C. et al. (2004) MicroRNA control of PHABULOSA in leaf development: Importance of pairing to the microRNA 5′ region. EMBO Journal 23: 3356–3364. [PMC free article: PMC514513] [PubMed: 15282547]
    298.
    Aukerman M.J. and Sakai H. (2003) Regulation of flowering time and floral organ identity by a microRNA and its APETALA2-like target genes. Plant Cell 15: 2730–2741. [PMC free article: PMC280575] [PubMed: 14555699]
    299.
    Blow M.J. et al. (2006) RNA editing of human microRNAs. Genome Biology 7: R27. [PMC free article: PMC1557993] [PubMed: 16594986]
    300.
    Fernandez-Valverde S.L., Taft R.J. and Mattick J.S. (2010) Dynamic isomiR regulation in Drosophila development. RNA 16: 1881–1888. [PMC free article: PMC2941097] [PubMed: 20805289]
    301.
    Calin G.A. et al. (2005) A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. New England Journal of Medicine 353: 1793–1801. [PubMed: 16251535]
    302.
    Hammond S.M. (2006) MicroRNAs as oncogenes. Current Opinion in Genetics and Development 16: 4–9. [PubMed: 16361094]
    303.
    Vannini I., Fanini F. and Fabbri M. (2018) Emerging roles of microRNAs in cancer. Current Opinion in Genetics and Development 48: 128–133. [PMC free article: PMC5986298] [PubMed: 29429825]
    304.
    Esquela-Kerscher A. and Slack F.J. (2006) Oncomirs - microRNAs with a role in cancer. Nature Reviews Cancer 6: 259–269. [PubMed: 16557279]
    305.
    Reynolds A. et al. (2006) Induction of the interferon response by siRNA is cell type- and duplex length-dependent. RNA 12: 988–993. [PMC free article: PMC1464853] [PubMed: 16611941]
    306.
    Zhao T. et al. (2007) A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii. Genes & Development 21: 1190–1203. [PMC free article: PMC1865491] [PubMed: 17470535]
    307.
    Hertel J. et al. (2006) The expansion of the metazoan microRNA repertoire. BMC Genomics 7: 25. [PMC free article: PMC1388199] [PubMed: 16480513]
    308.
    Prochnik S.E., Rokhsar D.S. and Aboobaker A.A. (2007) Evidence for a microRNA expansion in the bilaterian ancestor. Development Genes and Evolution 217: 73–77. [PubMed: 17103184]
    309.
    John B. et al. (2004) Human microRNA targets. PLOS Biology 2: e363. [PMC free article: PMC521178] [PubMed: 15502875]
    310.
    Lewis B.P., Burge C.B. and Bartel D.P. (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120: 15–20. [PubMed: 15652477]
    311.
    Baek D. et al. (2008) The impact of microRNAs on protein output. Nature 455: 64–71. [PMC free article: PMC2745094] [PubMed: 18668037]
    312.
    Lim L.P. et al. (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433: 769–773. [PubMed: 15685193]
    313.
    Friedman R.C., Farh K.K., Burge C.B. and Bartel D.P. (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Research 19: 92–105. [PMC free article: PMC2612969] [PubMed: 18955434]
    314.
    Didiano D. and Hobert O. (2006) Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nature Structural & Molecular Biology 13: 849–851. [PubMed: 16921378]
    315.
    Grimson A. et al. (2007) MicroRNA targeting specificity in mammals: Determinants beyond seed pairing. Molecular Cell 27: 91–105. [PMC free article: PMC3800283] [PubMed: 17612493]
    316.
    McGeary S.E. et al. (2019) The biochemical basis of microRNA targeting efficacy. Science 366: eaav1741. [PMC free article: PMC7051167] [PubMed: 31806698]
    317.
    Alberti C. and Cochella L. (2017) A framework for understanding the roles of miRNAs in animal development. Development 144: 2548–2559. [PubMed: 28720652]
    318.
    Sarshad A.A. et al. (2018) Argonaute-miRNA complexes silence target mRNAs in the nucleus of mammalian stem cells. Molecular Cell 71: 1040–1050. [PMC free article: PMC6690358] [PubMed: 30146314]
    319.
    Shuaib M. et al. (2019) Nuclear AGO1 regulates gene expression by affecting chromatin architecture in human cells. Cell Systems 9: 446–458. [PubMed: 31629687]
    320.
    Robb G.B., Brown K.M., Khurana J. and Rana T.M. (2005) Specific and potent RNAi in the nucleus of human cells. Nature Structural & Molecular Biology 12: 133–137. [PubMed: 15643423]
    321.
    Cesana M. et al. (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147: 358–369. [PMC free article: PMC3234495] [PubMed: 22000014]
    322.
    Wu H.J., Wang Z.M., Wang M. and Wang X.J. (2013) Wide-spread long non-coding RNAs (lncRNAs) as endogenous target mimics (eTMs) for microRNAs in plants. Plant Physiology 161: 1875–1884. [PMC free article: PMC3613462] [PubMed: 23429259]
    323.
    Memczak S. et al. (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495: 333–338. [PubMed: 23446348]
    324.
    Creasey K.M. et al. (2014) miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis. Nature 508: 411–415. [PMC free article: PMC4074602] [PubMed: 24670663]
    325.
    Borges F. et al. (2018) Transposon-derived small RNAs triggered by miR845 mediate genome dosage response in Arabidopsis. Nature Genetics 50: 186–192. [PMC free article: PMC5805582] [PubMed: 29335544]
    326.
    Bao N., Lye K.-W. and Barton M.K. (2004) MicroRNA binding sites in Arabidopsis class III HD-ZIP mRNAs are required for methylation of the template chromosome. Developmental Cell 7: 653–662. [PubMed: 15525527]
    327.
    Sinkkonen L. et al. (2008) MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells. Nature Structural & Molecular Biology 15: 259–267. [PubMed: 18311153]
    328.
    Wu H. et al. (2020) Plant 22-nt siRNAs mediate translational repression and stress adaptation. Nature 581: 89–93. [PubMed: 32376953]
    329.
    Tam O.H. et al. (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453: 534–538. [PMC free article: PMC2981145] [PubMed: 18404147]
    330.
    Watanabe T. et al. (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453: 539–543. [PubMed: 18404146]
    331.
    Sasidharan R. and Gerstein M. (2008) Protein fossils live on as RNA. Nature 453: 729–731. [PubMed: 18528383]
    332.
    Okamura K. and Lai E.C. (2008) Endogenous small interfering RNAs in animals. Nature Reviews Molecular Cell Biology 9: 673–678. [PMC free article: PMC2729316] [PubMed: 18719707]
    333.
    Aravin A.A. et al. (2001) Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Current Biology 11: 1017–1027. [PubMed: 11470406]
    334.
    Ketting R.F., Haverkamp T.H., van Luenen H.G. and Plasterk R.H. (1999) Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. Cell 99: 133–141. [PubMed: 10535732]
    335.
    Kawamura Y. et al. (2008) Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells. Nature 453: 793–797. [PubMed: 18463636]
    336.
    Czech B. et al. (2008) An endogenous small interfering RNA pathway in Drosophila. Nature 453: 798–802. [PMC free article: PMC2895258] [PubMed: 18463631]
    337.
    Okamura K. et al. (2008) The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature 453: 803–806. [PMC free article: PMC2735555] [PubMed: 18463630]
    338.
    Grivna S.T., Beyret E., Wang Z. and Lin H. (2006) A novel class of small RNAs in mouse spermatogenic cells. Genes & Development 20: 1709–1714. [PMC free article: PMC1522066] [PubMed: 16766680]
    339.
    Watanabe T. et al. (2006) Identification and characterization of two novel classes of small RNAs in the mouse germline: Retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes & Development 20: 1732–1743. [PMC free article: PMC1522070] [PubMed: 16766679]
    340.
    Girard A., Sachidanandam R., Hannon G.J. and Carmell M.A. (2006) A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442: 199–202. [PubMed: 16751776]
    341.
    Aravin A. et al. (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442: 203–207. [PubMed: 16751777]
    342.
    Lau N.C. et al. (2006) Characterization of the piRNA complex from rat testes. Science 313: 363–367. [PubMed: 16778019]
    343.
    Aravin A.A. et al. (2003) The small RNA profile during Drosophila melanogaster development. Developmental Cell 5: 337–350. [PubMed: 12919683]
    344.
    Lin H. and Spradling A.C. (1997) A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development 124: 2463–2476. [PubMed: 9199372]
    345.
    Kuramochi-Miyagawa S. et al. (2001) Two mouse piwi-related genes: miwi and mili. Mechanisms of Development 108: 121–133. [PubMed: 11578866]
    346.
    Ernst C., Odom D.T. and Kutter C. (2017) The emergence of piRNAs against transposon invasion to preserve mammalian genome integrity. Nature Communications 8: 1411. [PMC free article: PMC5681665] [PubMed: 29127279]
    347.
    Ji L. and Chen X. (2012) Regulation of small RNA stability: Methylation and beyond. Cell Research 22: 624–636. [PMC free article: PMC3317568] [PubMed: 22410795]
    348.
    Kirino Y. and Mourelatos Z. (2007) Mouse Piwi-interacting RNAs are 2′-O-methylated at their 3′ termini. Nature Structural & Molecular Biology 14: 347–348. [PubMed: 17384647]
    349.
    Simon B. et al. (2011) Recognition of 2′-O-methylated 3′-end of piRNA by the PAZ domain of a Piwi protein. Structure 19: 172–180. [PubMed: 21237665]
    350.
    Tian Y., Simanshu D.K., Ma J.-B. and Patel D.J. (2011) Structural basis for piRNA 2′-O-methylated 3′-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains. Proceedings of the National Academy of Sciences USA 108: 903–910. [PMC free article: PMC3024652] [PubMed: 21193640]
    351.
    Lakshmi S.S. and Agrawal S. (2008) piRNABank: A web resource on classified and clustered Piwi-interacting RNAs. Nucleic Acids Research 36: D173–7. [PMC free article: PMC2238943] [PubMed: 17881367]
    352.
    Özata D.M., Gainetdinov I., Zoch A., O’Carroll D. and Zamore P.D. (2019) PIWI-interacting RNAs: Small RNAs with big functions. Nature Reviews Genetics 20: 89–108. [PubMed: 30446728]
    353.
    Lau N.C. et al. (2009) Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line. Genome Research 19: 1776–1785. [PMC free article: PMC2765285] [PubMed: 19541914]
    354.
    Malone C.D. et al. (2009) Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. Cell 137: 522–535. [PMC free article: PMC2882632] [PubMed: 19395010]
    355.
    Kabayama Y. et al. (2017) Roles of MIWI, MILI and PLD6 in small RNA regulation in mouse growing oocytes. Nucleic Acids Research 45: 5387–5398. [PMC free article: PMC5435931] [PubMed: 28115634]
    356.
    Taborska E. et al. (2019) Restricted and non-essential redundancy of RNAi and piRNA pathways in mouse oocytes. PLOS Genetics 15: e1008261. [PMC free article: PMC6944382] [PubMed: 31860668]
    357.
    Rojas-Ríos P. and Simonelig M. (2018) piRNAs and PIWI proteins: Regulators of gene expression in development and stem cells. Development 145: dev161786. [PubMed: 30194260]
    358.
    Halbach R. et al. (2020) A satellite repeat-derived piRNA controls embryonic development of Aedes. Nature 580: 274–277. [PMC free article: PMC7145458] [PubMed: 32269344]
    359.
    Li C. et al. (2009) Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Cell 137: 509–521. [PMC free article: PMC2768572] [PubMed: 19395009]
    360.
    Rajasethupathy P. et al. (2012) A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 149: 693–707. [PMC free article: PMC3442366] [PubMed: 22541438]
    361.
    Moazed D. (2012) A piRNA to remember. Cell 149: 512–514. [PubMed: 22541425]
    362.
    Ghosheh Y. et al. (2016) Characterization of piRNAs across postnatal development in mouse brain. Scientific Reports 6: 25039. [PMC free article: PMC4844963] [PubMed: 27112104]
    363.
    Gasperini C. et al. (2020) The piRNA pathway sustains adult neurogenesis by repressing protein synthesis. bioRxiv: 2020.09.15.297739.
    364.
    Cheng Y. et al. (2019) Emerging roles of piRNAs in cancer: Challenges and prospects. Aging 11: 9932–9946. [PMC free article: PMC6874451] [PubMed: 31727866]
    365.
    Soper S.F.C. et al. (2008) Mouse Maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis. Developmental Cell 15: 285–297. [PMC free article: PMC2546488] [PubMed: 18694567]
    366.
    Nott T.J. et al. (2015) Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Molecular Cell 57: 936–947. [PMC free article: PMC4352761] [PubMed: 25747659]
    367.
    Aravin A.A., Sachidanandam R., Girard A., Fejes-Toth K. and Hannon G.J. (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316: 744–747. [PubMed: 17446352]
    368.
    Aravin A.A., Hannon G.J. and Brennecke J. (2007) The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science 318: 761–764. [PubMed: 17975059]
    369.
    Kuramochi-Miyagawa S. et al. (2008) DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes & Development 22: 908–917. [PMC free article: PMC2279202] [PubMed: 18381894]
    370.
    Jehn J. et al. (2018) PIWI genes and piRNAs are ubiquitously expressed in mollusks and show patterns of lineage-specific adaptation. Communications Biology 1: 137. [PMC free article: PMC6128900] [PubMed: 30272016]
    371.
    Zhang S., Pointer B. and Kelleher E. (2020) Rapid evolution of piRNA-mediated silencing of an invading transposable element was driven by abundant de novo mutations. Genome Research 30: 566–575. [PMC free article: PMC7197473] [PubMed: 32238416]
    372.
    Watanabe T. et al. (2011) Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332: 848–852. [PMC free article: PMC3368507] [PubMed: 21566194]
    373.
    Reddy H.M. et al. (2021) Y chromosomal noncoding RNAs regulate autosomal gene expression via piRNAs in mouse testis. BMC Biology 19: 198. [PMC free article: PMC8428117] [PubMed: 34503492]
    374.
    Pantano L. et al. (2015) The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein-coding genes. RNA 21: 1085–1095. [PMC free article: PMC4436662] [PubMed: 25904136]
    375.
    Robine N. et al. (2009) A broadly conserved pathway generates 3′UTR-directed primary piRNAs. Current Biology 19: 2066–2076. [PMC free article: PMC2812478] [PubMed: 20022248]
    376.
    Saito K. et al. (2009) A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila. Nature 461: 1296–1299. [PubMed: 19812547]
    377.
    Rigoutsos I. (2010) Short RNAs: How big is this iceberg? Current Biology 20: R110–3. [PubMed: 20144771]
    378.
    Guida V. et al. (2016) Production of small noncoding RNAs from the flamenco locus Is regulated by the gypsy retrotransposon of Drosophila melanogaster. Genetics 204: 631–644. [PMC free article: PMC5068851] [PubMed: 27558137]
    379.
    Sarkar A., Volff J.-N. and Vaury C. (2017) piRNAs and their diverse roles: A transposable element-driven tactic for gene regulation? FASEB Journal 31: 436–446. [PubMed: 27799346]
    380.
    Ohtani H. and Iwasaki Y.W. (2021) Rewiring of chromatin state and gene expression by transposable elements. Development, Growth & Differentiation 63: 262–273. [PubMed: 34050925]
    381.
    Iwasaki Y.W. et al. (2021) Piwi–piRNA complexes induce stepwise changes in nuclear architecture at target loci. EMBO Journal 40: e108345. [PMC free article: PMC8441340] [PubMed: 34337769]
    382.
    Zheng K. and Wang P.J. (2012) Blockade of pachytene piRNA biogenesis reveals a novel requirement for maintaining post-meiotic germline genome integrity. PLOS Genetics 8: e1003038. [PMC free article: PMC3499362] [PubMed: 23166510]
    383.
    Quénerch’du E., Anand A. and Kai T. (2016) The piRNA pathway is developmentally regulated during spermatogenesis in Drosophila. RNA 22: 1044–1054. [PMC free article: PMC4911912] [PubMed: 27208314]
    384.
    Gan H. et al. (2011) piRNA profiling during specific stages of mouse spermatogenesis. RNA 17: 1191–1203. [PMC free article: PMC3138557] [PubMed: 21602304]
    385.
    Czech B. et al. (2018) piRNA-guided genome defense: From biogenesis to silencing. Annual Review of Genetics 52: 131–157. [PubMed: 30476449]
    386.
    Werner A., Piatek M.J. and Mattick J.S. (2015) Transpositional shuffling and quality control in male germ cells to enhance evolution of complex organisms. Annals of the New York Academy of Sciences 1341: 156–163. [PMC free article: PMC4390386] [PubMed: 25557795]
    387.
    Werner A. et al. (2021) Widespread formation of double-stranded RNAs in testis. Genome Research 31: 1174–1186. [PMC free article: PMC8256860] [PubMed: 34158368]
    388.
    Goh W.S.S. et al. (2015) piRNA-directed cleavage of meiotic transcripts regulates spermatogenesis. Genes & Development 29: 1032–1044. [PMC free article: PMC4441051] [PubMed: 25995188]
    389.
    Wu P.-H. et al. (2020) The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility. Nature Genetics 52: 728–739. [PMC free article: PMC7383350] [PubMed: 32601478]
    390.
    Barucci G. et al. (2020) Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants. Nature Cell Biology 22: 235–245. [PMC free article: PMC7272227] [PubMed: 32015436]
    391.
    Lambert M., Benmoussa A. and Provost P. (2019) Small non-coding RNAs derived from eukaryotic ribosomal RNA. Noncoding RNA 5: 16. [PMC free article: PMC6468398] [PubMed: 30720712]
    392.
    Cherlin T. et al. (2020) Ribosomal RNA fragmentation into short RNAs (rRFs) is modulated in a sex- and population of origin-specific manner. BMC Biology 18: 38. [PMC free article: PMC7153239] [PubMed: 32279660]
    393.
    Guan L. and Grigoriev A. (2021) Computational meta-analysis of ribosomal RNA fragments: Potential targets and interaction mechanisms. Nucleic Acids Research 49: 4085–4103. [PMC free article: PMC8053083] [PubMed: 33772581]
    394.
    Lee H.C. et al. (2009) qiRNA is a new type of small interfering RNA induced by DNA damage. Nature 459: 274–277. [PMC free article: PMC2859615] [PubMed: 19444217]
    395.
    Francia S. et al. (2012) Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature 488: 231–235. [PMC free article: PMC3442236] [PubMed: 22722852]
    396.
    Michelini F. et al. (2017) Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Nature Cell Biology 19: 1400–1411. [PMC free article: PMC5714282] [PubMed: 29180822]
    397.
    Pessina F. et al. (2019) Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors. Nature Cell Biology 21: 1286–1299. [PMC free article: PMC6859070] [PubMed: 31570834]
    398.
    Wahba L., Hansen L. and Fire A.Z. (2021) An essential role for the piRNA pathway in regulating the ribosomal RNA pool in C. elegans. Developmental Cell 56: 2295–2312. [PMC free article: PMC8387450] [PubMed: 34388368]
    399.
    Kawaji H. et al. (2008) Hidden layers of human small RNAs. BMC Genomics 9: 157. [PMC free article: PMC2359750] [PubMed: 18402656]
    400.
    Cole C. et al. (2009) Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA 15: 2147–2160. [PMC free article: PMC2779667] [PubMed: 19850906]
    401.
    Lee Y.S., Shibata Y., Malhotra A. and Dutta A. (2009) A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes & Development 23: 2639–2649. [PMC free article: PMC2779758] [PubMed: 19933153]
    402.
    Anderson P. and Ivanov P. (2014) tRNA fragments in human health and disease. FEBS Letters 588: 4297–4304. [PMC free article: PMC4339185] [PubMed: 25220675]
    403.
    Pederson T. (2010) Regulatory RNAs derived from transfer RNA? RNA 16: 1865–1869. [PMC free article: PMC2941095] [PubMed: 20719919]
    404.
    Bracken C.P. et al. (2011) Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage. Nucleic Acids Research 39: 5658–5668. [PMC free article: PMC3141239] [PubMed: 21427086]
    405.
    Krishna S. et al. (2019) Dynamic expression of tRNA-derived small RNAs define cellular states. EMBO Reports 20: e47789. [PMC free article: PMC6607006] [PubMed: 31267708]
    406.
    Torres A.G., Reina O., Stephan-Otto Attolini C. and Ribas de Pouplana L. (2019) Differential expression of human tRNA genes drives the abundance of tRNA-derived fragments. Proceedings of the National Academy of Sciences USA 116: 8451–8456. [PMC free article: PMC6486751] [PubMed: 30962382]
    407.
    Yeung M.L. et al. (2009) Pyrosequencing of small non-coding RNAs in HIV-1 infected cells: Evidence for the processing of a viral-cellular double-stranded RNA hybrid. Nucleic Acids Research 37: 6575–6586. [PMC free article: PMC2770672] [PubMed: 19729508]
    408.
    Haussecker D. et al. (2010) Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA 16: 673–695. [PMC free article: PMC2844617] [PubMed: 20181738]
    409.
    Li Z. et al. (2012) Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs. Nucleic Acids Research 40: 6787–6799. [PMC free article: PMC3413118] [PubMed: 22492706]
    410.
    Maute R.L. et al. (2013) tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proceedings of the National Academy of Sciences USA 110: 1404–1409. [PMC free article: PMC3557069] [PubMed: 23297232]
    411.
    Kuscu C. et al. (2018) tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA 24: 1093–1105. [PMC free article: PMC6049499] [PubMed: 29844106]
    412.
    Schaefer M. et al. (2010) RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes & Development 24: 1590–1595. [PMC free article: PMC2912555] [PubMed: 20679393]
    413.
    Blanco S. et al. (2014) Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO Journal 33: 2020–2039. [PMC free article: PMC4195770] [PubMed: 25063673]
    414.
    He C. et al. (2021) TET2 chemically modifies tRNAs and regulates tRNA fragment levels. Nature Structural & Molecular Biology 28: 62–70. [PMC free article: PMC7855721] [PubMed: 33230319]
    415.
    Thompson D.M., Lu C., Green P.J. and Parker R. (2008) tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA 14: 2095–2103. [PMC free article: PMC2553748] [PubMed: 18719243]
    416.
    Yamasaki S., Ivanov P., Hu G.-F. and Anderson P. (2009) Angiogenin cleaves tRNA and promotes stress-induced translational repression. Journal of Cell Biology 185: 35–42. [PMC free article: PMC2700517] [PubMed: 19332886]
    417.
    Ivanov P., Emara M.M., Villen J., Gygi S.P. and Anderson P. (2011) Angiogenin-Induced tRNA fragments inhibit translation initiation. Molecular Cell 43: 613–623. [PMC free article: PMC3160621] [PubMed: 21855800]
    418.
    Sobala A. and Hutvagner G. (2013) Small RNAs derived from the 5′ end of tRNA can inhibit protein translation in human cells. RNA Biology 10: 553–563. [PMC free article: PMC3710361] [PubMed: 23563448]
    419.
    Vitali P. and Kiss T. (2019) Cooperative 2′-O-methylation of the wobble cytidine of human elongator tRNAMet(CAT) by a nucleolar and a Cajal body-specific box C/D RNP. Genes & Development 33: 741–746. [PMC free article: PMC6601510] [PubMed: 31171702]
    420.
    Sharma U. et al. (2016) Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science 351: 391–396. [PMC free article: PMC4888079] [PubMed: 26721685]
    421.
    Schorn A.J., Gutbrod M.J., LeBlanc C. and Martienssen R. (2017) LTR-retrotransposon control by tRNA-derived small RNAs. Cell 170: 61–71. [PMC free article: PMC5551035] [PubMed: 28666125]
    422.
    Hsieh L.-C., Lin S.-I., Kuo H.-F. and Chiou T.-J. (2010) Abundance of tRNA-derived small RNAs in phosphate-starved Arabidopsis roots. Plant Signaling & Behavior 5: 537–539. [PMC free article: PMC7080466] [PubMed: 20404547]
    423.
    Ren B., Wang X., Duan J. and Ma J. (2019) Rhizobial tRNA-derived small RNAs are signal molecules regulating plant nodulation. Science 365: 919–922. [PubMed: 31346137]
    424.
    Baglio S.R. et al. (2015) Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species. Stem Cell Research & Therapy 6: 127. [PMC free article: PMC4529699] [PubMed: 26129847]
    425.
    Chiou N.-T., Kageyama R. and Ansel K.M. (2018) Selective export into extracellular vesicles and function of tRNA fragments during T cell activation. Cell Reports 25: 3356–3370. [PMC free article: PMC6392044] [PubMed: 30566862]
    426.
    Peng H. et al. (2012) A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm. Cell Research 22: 1609–1612. [PMC free article: PMC3494397] [PubMed: 23044802]
    427.
    Vojtech L. et al. (2014) Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Research 42: 7290–7304. [PMC free article: PMC4066774] [PubMed: 24838567]
    428.
    Chen Q. et al. (2016) Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351: 397–400. [PubMed: 26721680]
    429.
    Gapp K. and Miska E.A. (2016) tRNA fragments: Novel players in intergenerational inheritance. Cell Research 26: 395–396. [PMC free article: PMC4822125] [PubMed: 26902286]
    430.
    Zhang Y. et al. (2018) Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nature Cell Biology 20: 535–540. [PMC free article: PMC5926820] [PubMed: 29695786]
    431.
    Boskovic A., Bing X.Y., Kaymak E. and Rando O.J. (2020) Control of noncoding RNA production and histone levels by a 5′ tRNA fragment. Genes & Development 34: 118–131. [PMC free article: PMC6938667] [PubMed: 31831626]
    432.
    Wilusz J.E., Freier S.M. and Spector D.L. (2008) 3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell 135: 919–932. [PMC free article: PMC2722846] [PubMed: 19041754]
    433.
    Lu X. et al. (2020) The tRNA-like small noncoding RNA mascRNA promotes global protein translation. EMBO Reports 21: e49684. [PMC free article: PMC7726780] [PubMed: 33073493]
    434.
    Zhang B. et al. (2017) Identification and characterization of a class of MALAT1-like genomic loci. Cell Reports 19: 1723–1738. [PMC free article: PMC5505346] [PubMed: 28538188]
    435.
    Ender C. et al. (2008) A human snoRNA with microRNA-like functions. Molecular Cell 32: 519–528. [PubMed: 19026782]
    436.
    Taft R.J. et al. (2009) Small RNAs derived from snoRNAs. RNA 15: 1233–1240. [PMC free article: PMC2704076] [PubMed: 19474147]
    437.
    Saraiya A.A. and Wang C.C. (2008) snoRNA, a novel precursor of microRNA in Giardia lamblia. PLOS Pathogens 4: e1000224. [PMC free article: PMC2583053] [PubMed: 19043559]
    438.
    Scott M.S., Avolio F., Ono M., Lamond A.I. and Barton G.J. (2009) Human miRNA precursors with box H/ACA snoRNA features. PLOS Computational Biology 5: e1000507. [PMC free article: PMC2730528] [PubMed: 19763159]
    439.
    Patterson D.G. et al. (2017) Human snoRNA-93 is processed into a microRNA-like RNA that promotes breast cancer cell invasion. Breast Cancer 3: 25. [PMC free article: PMC5503938] [PubMed: 28702505]
    440.
    Hussain S. et al. (2013) NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Reports 4: 255–261. [PMC free article: PMC3730056] [PubMed: 23871666]
    441.
    Hansen T.B. et al. (2016) Argonaute-associated short introns are a novel class of gene regulators. Nature Communications 7: 11538. [PMC free article: PMC4869172] [PubMed: 27173734]
    442.
    Taft R.J. et al. (2009) Tiny RNAs associated with transcription start sites in animals. Nature Genetics 41: 572–578. [PubMed: 19377478]
    443.
    Taft R.J., Kaplan C.D., Simons C. and Mattick J.S. (2009) Evolution, biogenesis and function of promoter-associated RNAs. Cell Cycle 8: 2332–2338. [PubMed: 19597344]
    444.
    Taft R.J. et al. (2010) Nuclear-localized tiny RNAs are associated with transcription initiation and splice sites in metazoans. Nature Structural & Molecular Biology 17: 1030–1034. [PubMed: 20622877]
    445.
    Timmons L. and Fire A. (1998) Specific interference by ingested dsRNA. Nature 395: 854. [PubMed: 9804418]
    446.
    Moriano-Gutierrez S. et al. (2020) The noncoding small RNA SsrA is released by Vibrio fischeri and modulates critical host responses. PLOS Biology 18: e3000934. [PMC free article: PMC7665748] [PubMed: 33141816]
    447.
    Kaletsky R. et al. (2020) C. elegans interprets bacterial non-coding RNAs to learn pathogenic avoidance. Nature 586: 445–451. [PMC free article: PMC8547118] [PubMed: 32908307]
    448.
    Moore R.S. et al. (2021) The role of the Cer1 transposon in horizontal transfer of transgenerational memory. Cell 184: 4697–4712. [PMC free article: PMC8812995] [PubMed: 34363756]
    449.
    Pagliuso A. et al. (2019) An RNA-binding protein secreted by a bacterial pathogen modulates RIG-I signaling. Cell Host & Microbe 26: 823–835. [PMC free article: PMC6907008] [PubMed: 31761719]
    450.
    Wong-Bajracharya J. et al. (2022) The ectomycorrhizal fungus Pisolithus microcarpus encodes a microRNA involved in cross-kingdom gene silencing during symbiosis. Proceedings of the National Academy of Sciences USA 119: e2103527119. [PMC free article: PMC8784151] [PubMed: 35012977]
    451.
    Porquier A. et al. (2021) Retrotransposons as pathogenicity factors of the plant pathogenic fungus Botrytis cinerea. Genome Biology 22: 225. [PMC free article: PMC8365987] [PubMed: 34399815]
    452.
    Jayasinghe W.H., Kim H., Nakada Y. and Masuta C. (2021) A plant virus satellite RNA directly accelerates wing formation in its insect vector for spread. Nature Communications 12: 7087. [PMC free article: PMC8648847] [PubMed: 34873158]
    453.
    Sarkies P. and Miska E.A. (2013) Is there social RNA? Science 341: 467–468. [PubMed: 23908213]
    454.
    Chen X. and Rechavi O. (2021) Plant and animal small RNA communications between cells and organisms. Nature Reviews Molecular Cell Biology 23: 185–203. [PMC free article: PMC9208737] [PubMed: 34707241]
    455.
    Buck A.H. et al. (2014) Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nature Communications 5: 5488. [PMC free article: PMC4263141] [PubMed: 25421927]
    456.
    Cai Q. et al. (2018) Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes. Science 360: 1126–1129. [PMC free article: PMC6442475] [PubMed: 29773668]
    457.
    Betti F. et al. (2021) Exogenous miRNAs induce post-transcriptional gene silencing in plants. Nature Plants 7: 1379–1388. [PMC free article: PMC8516643] [PubMed: 34650259]
    458.
    Shahid S. et al. (2018) MicroRNAs from the parasitic plant Cuscuta campestris target host messenger RNAs. Nature 553: 82–85. [PubMed: 29300014]
    459.
    Maori E. et al. (2019) A transmissible RNA pathway in honey bees. Cell Reports 27: 1949–1959. [PubMed: 31056439]
    460.
    Maori E. et al. (2019) A secreted RNA binding protein forms RNA-stabilizing granules in the honeybee royal jelly. Molecular Cell 74: 598–608. [PMC free article: PMC6509358] [PubMed: 31051140]
    461.
    Hunter W. et al. (2010) Large-scale field application of RNAi technology reducing Israeli acute paralysis virus disease in honey bees (Apis mellifera, Hymenoptera: Apidae). PLOS Pathogens 6: e1001160. [PMC free article: PMC3009593] [PubMed: 21203478]
    462.
    Lampson B.C. et al. (1989) Reverse transcriptase in a clinical strain of Escherichia coli: Production of branched RNA-linked msDNA. Science 243: 1033–1038. [PubMed: 2466332]
    463.
    Lim D. and Maas W.K. (1989) Reverse transcriptase-dependent synthesis of a covalently linked, branched DNA-RNA compound in E. coli B. Cell 56: 891–904. [PubMed: 2466573]
    464.
    Temin H.M. (1989) Retrons in bacteria. Nature 339: 254–255. [PubMed: 2471077]
    465.
    Millman A. et al. (2020) Bacterial retrons function in anti-phage defense. Cell 183: 1551–1561. [PubMed: 33157039]
    466.
    van der Oost J., Westra E.R., Jackson R.N. and Wiedenheft B. (2014) Unravelling the structural and mechanistic basis of CRISPR–Cas systems. Nature Reviews Microbiology 12: 479–492. [PMC free article: PMC4225775] [PubMed: 24909109]
    467.
    Marraffini L.A. (2015) CRISPR-Cas immunity in prokaryotes. Nature 526: 55–61. [PubMed: 26432244]
    468.
    Mojica F.J.M. and Rodriguez-Valera F. (2016) The discovery of CRISPR in archaea and bacteria. FEBS Journal 283: 3162–3169. [PubMed: 27234458]
    469.
    Lander E.S. (2016) The heroes of CRISPR. Cell 164: 18–28. [PubMed: 26771483]
    470.
    Ishino Y., Krupovic M. and Forterre P. (2018) History of CRISPR-Cas from encounter with a mysterious repeated sequence to genome editing technology. Journal of Bacteriology 200: e00580. [PMC free article: PMC5847661] [PubMed: 29358495]
    471.
    Ishino Y., Shinagawa H., Makino K., Amemura M. and Nakata A. (1987) Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. Journal of Bacteriology 169: 5429–5433. [PMC free article: PMC213968] [PubMed: 3316184]
    472.
    Mojica F.J.M., Ferrer C., Juez G. and Rodríguez-Valera F. (1995) Long stretches of short tandem repeats are present in the largest replicons of the Archaea Haloferax mediterranei and Haloferax volcanii and could be involved in replicon partitioning. Molecular Microbiology 17: 85–93. [PubMed: 7476211]
    473.
    Mojica F.J.M., Díez-Villaseñor C., Soria E. and Juez G. (2000) Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Molecular Microbiology 36: 244–246. [PubMed: 10760181]
    474.
    Jansen R., Van Embden J.D.A., Gaastra W. and Schouls L.M. (2002) Identification of genes that are associated with DNA repeats in prokaryotes. Molecular Microbiology 43: 1565–1575. [PubMed: 11952905]
    475.
    Gasiunas G., Barrangou R., Horvath P. and Siksnys V. (2012) Cas9–crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proceedings of the National Academy of Sciences USA 109: E2579–86. [PMC free article: PMC3465414] [PubMed: 22949671]
    476.
    Ledford H. (2016) The unsung heroes of CRISPR. Nature 535: 342–344. [PubMed: 27443723]
    477.
    Mojica F.J.M., Díez-Villaseñor C.S., García-Martínez J. and Soria E. (2005) Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. Journal of Molecular Evolution 60: 174–182. [PubMed: 15791728]
    478.
    Pourcel C., Salvignol G. and Vergnaud G. (2005) CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology 151: 653–663. [PubMed: 15758212]
    479.
    Bolotin A., Quinquis B., Sorokin A. and Ehrlich S.D. (2005) Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151: 2551–2561. [PubMed: 16079334]
    480.
    Makarova K.S., Grishin N.V., Shabalina S.A., Wolf Y.I. and Koonin E.V. (2006) A putative RNA-interference-based immune system in prokaryotes: Computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biology Direct 1: 7. [PMC free article: PMC1462988] [PubMed: 16545108]
    481.
    Barrangou R. et al. (2007) CRISPR provides acquired resistance against viruses in prokaryotes. Science 315: 1709–1712. [PubMed: 17379808]
    482.
    Brouns S.J.J. et al. (2008) Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321: 960–964. [PMC free article: PMC5898235] [PubMed: 18703739]
    483.
    Horvath P. et al. (2008) Diversity, activity, and evolution of CRISPR loci in Streptococcus thermophilus. Journal of Bacteriology 190: 1401–1412. [PMC free article: PMC2238196] [PubMed: 18065539]
    484.
    Deveau H. et al. (2008) Phage response to CRISPR-encoded resistance in Streptococcus thermophilus. Journal of Bacteriology 190: 1390–1400. [PMC free article: PMC2238228] [PubMed: 18065545]
    485.
    Jinek M. et al. (2012) A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science 337: 816–821. [PMC free article: PMC6286148] [PubMed: 22745249]
    486.
    Jiang F. and Doudna J.A. (2017) CRISPR–Cas9 structures and mechanisms. Annual Review of Biophysics 46: 505–529. [PubMed: 28375731]
    487.
    Marraffini L.A. and Sontheimer E.J. (2008) CRISPR interference limits horizontal gene transfer in Staphylococci by targeting DNA. Science 322: 1843–1845. [PMC free article: PMC2695655] [PubMed: 19095942]
    488.
    Garneau J.E. et al. (2010) The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 468: 67–71. [PubMed: 21048762]
    489.
    Altae-Tran H. et al. (2021) The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases. Science 374: 57–65. [PMC free article: PMC8929163] [PubMed: 34591643]
    490.
    Saito M. et al. (2021) Dual modes of CRISPR-associated transposon homing. Cell 184: 2441–2453. [PMC free article: PMC8276595] [PubMed: 33770501]
    491.
    Mangold M. et al. (2004) Synthesis of group A streptococcal virulence factors is controlled by a regulatory RNA molecule. Molecular Microbiology 53: 1515–1527. [PubMed: 15387826]
    492.
    Deltcheva E. et al. (2011) CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471: 602–607. [PMC free article: PMC3070239] [PubMed: 21455174]
    493.
    Workman R.E. et al. (2021) A natural single-guide RNA repurposes Cas9 to autoregulate CRISPR-Cas expression. Cell 184: 675–688. [PubMed: 33421369]
    494.
    Rees H.A. and Liu D.R. (2018) Base editing: Precision chemistry on the genome and transcriptome of living cells. Nature Reviews Genetics 19: 770–788. [PMC free article: PMC6535181] [PubMed: 30323312]
    495.
    Pickar-Oliver A. and Gersbach C.A. (2019) The next generation of CRISPR–Cas technologies and applications. Nature Reviews Molecular Cell Biology 20: 490–507. [PMC free article: PMC7079207] [PubMed: 31147612]
    496.
    Haft D.H., Selengut J., Mongodin E.F. and Nelson K.E. (2005) A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes. PLOS Computational Biology 1: e60. [PMC free article: PMC1282333] [PubMed: 16292354]
    497.
    Harrington L.B. et al. (2018) Programmed DNA destruction by miniature CRISPR-Cas14 enzymes. Science 362: 839–842. [PMC free article: PMC6659742] [PubMed: 30337455]
    498.
    Sapranauskas R. et al. (2011) The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucleic Acids Research 39: 9275–9282. [PMC free article: PMC3241640] [PubMed: 21813460]
    499.
    Koonin E.V. and Makarova K.S. (2022) Evolutionary plasticity and functional versatility of CRISPR systems. PLOS Biology 20: e3001481. [PMC free article: PMC8730458] [PubMed: 34986140]
    500.
    Cong L. et al. (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339: 819–823. [PMC free article: PMC3795411] [PubMed: 23287718]
    501.
    Mali P. et al. (2013) RNA-guided human genome engineering via Cas9. Science 339: 823–826. [PMC free article: PMC3712628] [PubMed: 23287722]
    502.
    Cui X. and Davis G. (2007) Mobile group II intron targeting: Applications in prokaryotes and perspectives in eukaryotes. Frontiers in Bioscience 12: 4972–4985. [PubMed: 17569624]
    503.
    Lambowitz A.M. and Zimmerly S. (2011) Group II introns: Mobile ribozymes that invade DNA. Cold Spring Harbor Perspectives in Biology 3: a003616. [PMC free article: PMC3140690] [PubMed: 20463000]
    504.
    Belfort M. and Bonocora R.P. (2014) Homing endonucleases: From genetic anomalies to programmable genomic clippers, in D. Edgell (ed.) Homing Endonucleases: Methods and Protocols (Humana Press, New York). [PMC free article: PMC4436680] [PubMed: 24510256]
    505.
    Burt A. (2003) Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proceedings of the Royal Society B: Biological Sciences 270: 921–928. [PMC free article: PMC1691325] [PubMed: 12803906]
    506.
    Wood A.J. et al. (2011) Targeted genome editing across species using ZFNs and TALENs. Science 333: 307. [PMC free article: PMC3489282] [PubMed: 21700836]
    507.
    Kim E. et al. (2012) Precision genome engineering with programmable DNA-nicking enzymes. Genome Research 22: 1327–1333. [PMC free article: PMC3396373] [PubMed: 22522391]
    508.
    Gaj T., Gersbach C.A. and Barbas III C.F., (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends in Biotechnology 31: 397–405. [PMC free article: PMC3694601] [PubMed: 23664777]
    509.
    Chen B. et al. (2013) Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155: 1479–1491. [PMC free article: PMC3918502] [PubMed: 24360272]
    510.
    Zetsche B. et al. (2015) Cpf1 Is a single RNA-guided endonuclease of a class 2 CRISPR-Cas System. Cell 163: 759–771. [PMC free article: PMC4638220] [PubMed: 26422227]
    511.
    Abudayyeh O.O. et al. (2017) RNA targeting with CRISPR-Cas13. Nature 550: 280–284. [PMC free article: PMC5706658] [PubMed: 28976959]
    512.
    Wang H. et al. (2019) CRISPR-mediated live imaging of genome editing and transcription. Science 365: 1301–1305. [PubMed: 31488703]
    513.
    Li Y., Li S., Wang J. and Liu G. (2019) CRISPR/Cas systems towards next-generation biosensing. Trends in Biotechnology 37: 730–743. [PubMed: 30654914]
    514.
    Smargon A.A., Shi Y.J. and Yeo G.W. (2020) RNA-targeting CRISPR systems from metagenomic discovery to transcriptomic engineering. Nature Cell Biology 22: 143–150. [PMC free article: PMC8008746] [PubMed: 32015437]
    515.
    Liu H. et al. (2020) High-throughput CRISPR/Cas9 mutagenesis streamlines trait gene identification in maize. Plant Cell 32: 1397–1413. [PMC free article: PMC7203946] [PubMed: 32102844]
    516.
    Donohoue P.D., Barrangou R. and May A.P. (2018) Advances in industrial biotechnology using CRISPR-Cas systems. Trends in Biotechnology 36: 134–146. [PubMed: 28778606]
    517.
    Zhang S. et al. (2020) Recent advances of CRISPR/Cas9-based genetic engineering and transcriptional regulation in industrial biology. Frontiers in Bioengineering and Biotechnology 7: 459. [PMC free article: PMC6997136] [PubMed: 32047743]
    518.
    Jaganathan D., Ramasamy K., Sellamuthu G., Jayabalan S. and Venkataraman G. (2018) CRISPR for crop improvement: An update review. Frontiers in Plant Science 9: 985. [PMC free article: PMC6056666] [PubMed: 30065734]
    519.
    Lin Q. et al. (2020) Prime genome editing in rice and wheat. Nature Biotechnology 38: 582–585. [PubMed: 32393904]
    520.
    Knott G.J. and Doudna J.A. (2018) CRISPR-Cas guides the future of genetic engineering. Science 361: 866–869. [PMC free article: PMC6455913] [PubMed: 30166482]
    521.
    Liu X.S. et al. (2016) Editing DNA methylation in the mammalian genome. Cell 167: 233–247. [PMC free article: PMC5062609] [PubMed: 27662091]
    522.
    McDonald J.I. et al. (2016) Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation. Biology Open 5: 866–874. [PMC free article: PMC4920199] [PubMed: 27170255]
    523.
    Klann T.S. et al. (2017) CRISPR–Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome. Nature Biotechnology 35: 561–568. [PMC free article: PMC5462860] [PubMed: 28369033]
    524.
    Lei Y., Huang Y.-H. and Goodell M.A. (2018) DNA methylation and de-methylation using hybrid site-targeting proteins. Genome Biology 19: 187. [PMC free article: PMC6219187] [PubMed: 30400938]
    525.
    Kang J.G., Park J.S., Ko J.-H. and Kim Y.-S. (2019) Regulation of gene expression by altered promoter methylation using a CRISPR/Cas9-mediated epigenetic editing system. Scientific Reports 9: 11960. [PMC free article: PMC6700181] [PubMed: 31427598]
    526.
    Devesa-Guerra I. et al. (2020) DNA methylation editing by CRISPR-guided excision of 5-methylcytosine. Journal of Molecular Biology 432: 2204–2216. [PubMed: 32087201]
    527.
    Gilbert L.A. et al. (2013) CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154: 442–451. [PMC free article: PMC3770145] [PubMed: 23849981]
    528.
    Perez-Pinera P. et al. (2013) RNA-guided gene activation by CRISPR-Cas9–based transcription factors. Nature Methods 10: 973–976. [PMC free article: PMC3911785] [PubMed: 23892895]
    529.
    Konermann S. et al. (2015) Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517: 583–588. [PMC free article: PMC4420636] [PubMed: 25494202]
    530.
    Chavez A. et al. (2015) Highly efficient Cas9-mediated transcriptional programming. Nature Methods 12: 326–328. [PMC free article: PMC4393883] [PubMed: 25730490]
    531.
    Yeo N.C. et al. (2018) An enhanced CRISPR repressor for targeted mammalian gene regulation. Nature Methods 15: 611–616. [PMC free article: PMC6129399] [PubMed: 30013045]
    532.
    Komor A.C., Kim Y.B., Packer M.S., Zuris J.A. and Liu D.R. (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533: 420–424. [PMC free article: PMC4873371] [PubMed: 27096365]
    533.
    Gaudelli N.M. et al. (2017) Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551: 464–471. [PMC free article: PMC5726555] [PubMed: 29160308]
    534.
    Anzalone A.V. et al. (2019) Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576: 149–157. [PMC free article: PMC6907074] [PubMed: 31634902]
    535.
    Anzalone A.V. et al. (2021) Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing. Nature Biotechnology epub ahead of print: https://www​.nature.com​/articles/s41587-021-01133-w. [PMC free article: PMC9117393] [PubMed: 34887556]
    536.
    Staahl B.T. et al. (2017) Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes. Nature Biotechnology 35: 431–434. [PMC free article: PMC6649674] [PubMed: 28191903]
    537.
    Yeh W.-H. et al. (2020) In vivo base editing restores sensory transduction and transiently improves auditory function in a mouse model of recessive deafness. Science Translational Medicine 12: eaay9101. [PMC free article: PMC8167884] [PubMed: 32493795]
    538.
    Gillmore J.D. et al. (2021) CRISPR-Cas9 In vivo gene editing for Transthyretin Amyloidosis. New England Journal of Medicine 385: 493–502. [PubMed: 34215024]
    539.
    Özcan A. et al. (2021) Programmable RNA targeting with the single-protein CRISPR effector Cas7–11. Nature 597: 720–725. [PubMed: 34489594]
    540.
    Montiel-Gonzalez M.F., Vallecillo-Viejo I., Yudowski G.A. and Rosenthal J.J.C. (2013) Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing. Proceedings of the National Academy of Sciences USA 110: 18285–18290. [PMC free article: PMC3831439] [PubMed: 24108353]
    541.
    Sinnamon J.R. et al. (2017) Site-directed RNA repair of endogenous Mecp2 RNA in neurons. Proceedings of the National Academy of Sciences USA 114: E9395–402. [PMC free article: PMC5676935] [PubMed: 29078406]
    542.
    Vogel P. et al. (2018) Efficient and precise editing of endogenous transcripts with SNAP-tagged ADARs. Nature Methods 15: 535–538. [PMC free article: PMC6322650] [PubMed: 29967493]
    543.
    Cox D.B.T. et al. (2017) RNA editing with CRISPR-Cas13. Science 358: 1019–1027. [PMC free article: PMC5793859] [PubMed: 29070703]
    544.
    Gootenberg J.S. et al. (2018) Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science 360: 439–444. [PMC free article: PMC5961727] [PubMed: 29449508]
    545.
    Myhrvold C. et al. (2018) Field-deployable viral diagnostics using CRISPR-Cas13. Science 360: 444–448. [PMC free article: PMC6197056] [PubMed: 29700266]
    546.
    Jiao C. et al. (2021) Noncanonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9. Science 372: 941–948. [PMC free article: PMC8224270] [PubMed: 33906967]
    547.
    Curtis C.F. (1968) Possible use of translocations to fix desirable genes in insect pest populations. Nature 218: 368–369. [PubMed: 5649682]
    548.
    Curtis C.F. and Hill W.G. (1971) Theoretical studies on the use of translocations for the control of tsetse flies and other disease vectors. Theoretical Population Biology 2: 71–90. [PubMed: 5170715]
    549.
    Yan Y. and Finnigan G.C. (2018) Development of a multi-locus CRISPR gene drive system in budding yeast. Scientific Reports 8: 17277. [PMC free article: PMC6250742] [PubMed: 30467400]
    550.
    Yan Y. and Finnigan G.C. (2019) Analysis of CRISPR gene drive design in budding yeast. Access Microbiology 1: e000059. [PMC free article: PMC7472540] [PubMed: 32974560]
    551.
    Chan Y.-S., Naujoks D.A., Huen D.S. and Russell S. (2011) Insect population control by homing endonuclease-based gene drive: An evaluation in Drosophila melanogaster. Genetics 188: 33–44. [PMC free article: PMC3120159] [PubMed: 21368273]
    552.
    Windbichler N. et al. (2011) A synthetic homing endonuclease-based gene drive system in the human malaria mosquito. Nature 473: 212–215. [PMC free article: PMC3093433] [PubMed: 21508956]
    553.
    Gantz V.M. et al. (2015) Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proceedings of the National Academy of Sciences USA 112: E6736–43. [PMC free article: PMC4679060] [PubMed: 26598698]
    554.
    Hammond A. et al. (2016) A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nature Biotechnology 34: 78–83. [PMC free article: PMC4913862] [PubMed: 26641531]
    555.
    Esvelt K.M., Smidler A.L., Catteruccia F. and Church G.M. (2014) Concerning RNA-guided gene drives for the alteration of wild populations. eLife 3: e03401. [PMC free article: PMC4117217] [PubMed: 25035423]
    556.
    Champer J., Buchman A. and Akbari O.S. (2016) Cheating evolution: Engineering gene drives to manipulate the fate of wild populations. Nature Reviews Genetics 17: 146–159. [PubMed: 26875679]
    557.
    DiCarlo J.E., Chavez A., Dietz S.L., Esvelt K.M. and Church G.M. (2015) Safeguarding CRISPR-Cas9 gene drives in yeast. Nature Biotechnology 33: 1250–1255. [PMC free article: PMC4675690] [PubMed: 26571100]
    558.
    Roggenkamp E. et al. (2018) Tuning CRISPR-Cas9 in Saccharomyces cerevisiae. G3 (Genes, Genomes, Genetics) 8: 999–1018. [PMC free article: PMC5844318] [PubMed: 29348295]
    559.
    Noble C. et al. (2019) Daisy-chain gene drives for the alteration of local populations. Proceedings of the National Academy of Sciences USA 116: 8275–8282. [PMC free article: PMC6486765] [PubMed: 30940750]
    560.
    Xu X.S. et al. (2020) Active genetic neutralizing elements for halting or deleting gene drives. Molecular Cell 80: 246–262. [PubMed: 32949493]
    561.
    Wei T., Cheng Q., Min Y.-L., Olson E.N. and Siegwart D.J. (2020) Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing. Nature Communications 11: 3232. [PMC free article: PMC7320157] [PubMed: 32591530]
    562.
    Rosenblum D. et al. (2020) CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy. Science Advances 6: eabc9450. [PMC free article: PMC7673804] [PubMed: 33208369]
    563.
    Hou X., Zaks T., Langer R. and Dong Y. (2021) Lipid nanoparticles for mRNA delivery. Nature Reviews Materials 6: 1078–1094. [PMC free article: PMC8353930] [PubMed: 34394960]

    Chapter 13

    1.
    Storz G. (2002) An expanding universe of noncoding RNAs. Science 296: 1260–1263. [PubMed: 12016301]
    2.
    Storz G., Altuvia S. and Wassarman K.M. (2005) An abundance of RNA regulators. Annual Review of Biochemistry 74: 199–217. [PubMed: 15952886]
    3.
    Croft L. et al. (2000) ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome. Nature Genetics 24: 340–341. [PubMed: 10742092]
    4.
    Deveson I.W. et al. (2018) Universal alternative splicing of noncoding exons. Cell Systems 6: 245–255. [PubMed: 29396323]
    5.
    Graves P.R. and Haystead T.A.J. (2002) Molecular biologist’s guide to proteomics. Microbiology and Molecular Biology Reviews 66: 39–63. [PMC free article: PMC120780] [PubMed: 11875127]
    6.
    Ahmad Y. and Lamond A.I. (2014) A perspective on proteomics in cell biology. Trends in Cell Biology 24: 257–264. [PMC free article: PMC3989996] [PubMed: 24284280]
    7.
    Adams M.D., Soares M.B., Kerlavage A.R., Fields C. and Venter J.C. (1993) Rapid cDNA sequencing (expressed sequence tags) from a directionally cloned human infant brain cDNA library. Nature Genetics 4: 373–380. [PubMed: 8401585]
    8.
    Fields C., Adams M.D., White O. and Venter J.C. (1994) How many genes in the human genome? Nature Genetics 7: 345–346. [PubMed: 7920649]
    9.
    Adesnik M. and Darnell J.E. (1972) Biogenesis and characterization of histone messenger RNA in HeLa cells. Journal of Molecular Biology 67: 397–406. [PubMed: 5045304]
    10.
    Milcarek C., Price R. and Penman S. (1974) The metabolism of a poly(A) minus mRNA fraction in HeLa cells. Cell 3: 1–10. [PubMed: 4213457]
    11.
    Katinakis P.K., Slater A. and Burdon R.H. (1980) Non-polyadenylated mRNAs from eukaryotes. FEBS Letters 116: 1–7. [PubMed: 6997068]
    12.
    Salditt-Georgieff M., Harpold M.M., Wilson M.C. and Darnell Jr. J.E., (1981) Large heterogeneous nuclear ribonucleic acid has three times as many 5′ caps as polyadenylic acid segments, and most caps do not enter polyribosomes. Molecular Cell Biology 1: 179–187. [PMC free article: PMC369657] [PubMed: 6152852]
    13.
    Reis E.M. et al. (2004) Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer. Oncogene 23: 6684–6692. [PubMed: 15221013]
    14.
    Carninci P. et al. (2005) The transcriptional landscape of the mammalian genome. Science 309: 1559–1563. [PubMed: 16141072]
    15.
    Roest Crollius H. et al. (2000) Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence. Nature Genetics 25: 235–238. [PubMed: 10835645]
    16.
    Strausberg R.L., Feingold E.A., Klausner R.D. and Collins F.S. (1999) The mammalian gene collection. Science 286: 455–457. [PubMed: 10521335]
    17.
    Strausberg R.L. et al. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences USA 99: 16899–16903. [PMC free article: PMC139241] [PubMed: 12477932]
    18.
    Dias Neto E. et al. (2000) Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. Proceedings of the National Academy of Sciences USA 97: 3491–3496. [PMC free article: PMC16267] [PubMed: 10737800]
    19.
    de Souza S.J. et al. (2000) Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags. Proceedings of the National Academy of Sciences USA 97: 12690–12693. [PMC free article: PMC18825] [PubMed: 11070084]
    20.
    Camargo A.A. et al. (2001) The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome. Proceedings of the National Academy of Sciences USA 98: 12103–12108. [PMC free article: PMC59775] [PubMed: 11593022]
    21.
    Brentani H. et al. (2003) The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags. Proceedings of the National Academy of Sciences USA 100: 13418–13423. [PMC free article: PMC263829] [PubMed: 14593198]
    22.
    Deveson I.W., Hardwick S.A., Mercer T.R. and Mattick J.S. (2017) The dimensions, dynamics, and relevance of the mammalian noncoding transcriptome. Trends in Genetics 33: 464–478. [PubMed: 28535931]
    23.
    Bishop J.O., Morton J.G., Rosbash M. and Richardson M. (1974) Three abundance classes in HeLa cell messenger RNA. Nature 250: 199–204. [PubMed: 4855195]
    24.
    Coupar B.E., Davies J.A. and Chesterton C.J. (1978) Quantification of hepatic transcribing RNA polymerase molecules, polyribonucleotide elongation rates and messenger RNA complexity in fed and fasted rats. European Journal of Biochemistry 84: 611–623. [PubMed: 639806]
    25.
    Su A.I. et al. (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proceedings of the National Academy of Sciences USA 101: 6062–6067. [PMC free article: PMC395923] [PubMed: 15075390]
    26.
    Bonaldo M.F., Lennon G. and Soares M.B. (1996) Normalization and subtraction: Two approaches to facilitate gene discovery. Genome Research 6: 791–806. [PubMed: 8889548]
    27.
    Carninci P. et al. (2000) Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes. Genome Research 10: 1617–1630. [PMC free article: PMC310980] [PubMed: 11042159]
    28.
    Cheng J. et al. (2005) Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308: 1149–1154. [PubMed: 15790807]
    29.
    Carninci P. et al. (1996) High-efficiency full-length cDNA cloning by biotinylated CAP trapper. Genomics 37: 327–336. [PubMed: 8938445]
    30.
    Shiraki T. et al. (2003) Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage. Proceedings of the National Academy of Sciences USA 100: 15776–15781. [PMC free article: PMC307644] [PubMed: 14663149]
    31.
    Hirozane-Kishikawa T. et al. (2003) Subtraction of cap-trapped full-length cDNA libraries to select rare transcripts. Biotechniques 35: 510–518. [PubMed: 14513556]
    32.
    Carninci P. et al. (2003) Targeting a complex transcriptome: The construction of the mouse full-length cDNA encyclopedia. Genome Research 13: 1273–1289. [PMC free article: PMC403712] [PubMed: 12819125]
    33.
    de Hoon M., Shin J.W. and Carninci P. (2015) Paradigm shifts in genomics through the FANTOM projects. Mammalian Genome 26: 391–402. [PMC free article: PMC4602071] [PubMed: 26253466]
    34.
    Abugessaisa I. et al. (2021) FANTOM enters 20th year: Expansion of transcriptomic atlases and functional annotation of non-coding RNAs. Nucleic Acids Research 49: D892–8. [PMC free article: PMC7779024] [PubMed: 33211864]
    35.
    Okazaki Y. et al. (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420: 563–573. [PubMed: 12466851]
    36.
    Numata K. et al. (2003) Identification of putative noncoding RNAs among the RIKEN mouse full-length cDNA collection. Genome Research 13: 1301–1306. [PMC free article: PMC403720] [PubMed: 12819127]
    37.
    Ravasi T. et al. (2006) Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. Genome Research 16: 11–19. [PMC free article: PMC1356124] [PubMed: 16344565]
    38.
    Kiyosawa H., Yamanaka I., Osato N., Kondo S. and Hayashizaki Y. (2003) Antisense transcripts with FANTOM2 clone set and their implications for gene regulation. Genome Research 13: 1324–1334. [PMC free article: PMC403655] [PubMed: 12819130]
    39.
    Katayama S. et al. (2005) Antisense transcription in the mammalian transcriptome. Science 309: 156 4–6. [PubMed: 16141073]
    40.
    Dahary D., Elroy-Stein O. and Sorek R. (2005) Naturally occurring antisense: Transcriptional leakage or real overlap? Genome Research 15: 364–368. [PMC free article: PMC551562] [PubMed: 15710751]
    41.
    Shendure J. and Church G.M. (2002) Computational discovery of sense-antisense transcription in the human and mouse genomes. Genome Biology 3: 0044. [PMC free article: PMC126869] [PubMed: 12225583]
    42.
    Yelin R. et al. (2003) Widespread occurrence of antisense transcription in the human genome. Nature Biotechnology 21: 379–386. [PubMed: 12640466]
    43.
    Trinklein N.D. et al. (2004) An abundance of bidirectional promoters in the human genome. Genome Research 14: 62–66. [PMC free article: PMC314279] [PubMed: 14707170]
    44.
    Werner A. and Berdal A. (2005) Natural antisense transcripts: Sound or silence? Physiological Genomics 23: 125–131. [PubMed: 16230481]
    45.
    Engstrom P.G. et al. (2006) Complex loci in human and mouse genomes. PLOS Genetics 2: e47. [PMC free article: PMC1449890] [PubMed: 16683030]
    46.
    Nakaya H.I. et al. (2007) Genome mapping and expression analyses of human intronic noncoding RNAs reveal tissue-specific patterns and enrichment in genes related to regulation of transcription. Genome Biology 8: R43. [PMC free article: PMC1868932] [PubMed: 17386095]
    47.
    Xu Z. et al. (2009) Bidirectional promoters generate pervasive transcription in yeast. Nature 457: 1033–1037. [PMC free article: PMC2766638] [PubMed: 19169243]
    48.
    Ozsolak F. et al. (2010) Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation. Cell 143: 1018–1029. [PMC free article: PMC3022516] [PubMed: 21145465]
    49.
    Brown J.B. et al. (2014) Diversity and dynamics of the Drosophila transcriptome. Nature 512: 393–399. [PMC free article: PMC4152413] [PubMed: 24670639]
    50.
    Krzyczmonik K., Wroblewska-Swiniarska A. and Swiezewski S. (2017) Developmental transitions in Arabidopsis are regulated by antisense RNAs resulting from bidirectionally transcribed genes. RNA Biology 14: 838–842. [PMC free article: PMC5546715] [PubMed: 28513325]
    51.
    Zhao X. et al. (2018) Global identification of Arabidopsis lncRNAs reveals the regulation of MAF4 by a natural antisense RNA. Nature Communications 9: 5056. [PMC free article: PMC6265284] [PubMed: 30498193]
    52.
    Louro R., El-Jundi T., Nakaya H.I., Reis E.M. and Verjovski-Almeida S. (2008) Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci. Genomics 92: 18–25. [PubMed: 18495418]
    53.
    Johnson J.M., Edwards S., Shoemaker D. and Schadt E.E. (2005) Dark matter in the genome: Evidence of widespread transcription detected by microarray tiling experiments. Trends in Genetics 21: 93–102. [PubMed: 15661355]
    54.
    Kapranov P. et al. (2002) Large-scale transcriptional activity in chromosomes 21 and 22. Science 296: 916–919. [PubMed: 11988577]
    55.
    Rinn J.L. et al. (2003) The transcriptional activity of human chromosome 22. Genes & Development 17: 529–540. [PMC free article: PMC195998] [PubMed: 12600945]
    56.
    Bertone P. et al. (2004) Global identification of human transcribed sequences with genome tiling arrays. Science 306: 2242–2246. [PubMed: 15539566]
    57.
    Kapranov P. et al. (2005) Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. Genome Research 15: 987–997. [PMC free article: PMC1172043] [PubMed: 15998911]
    58.
    Efroni S. et al. (2008) Global transcription in pluripotent embryonic stem cells. Cell Stem Cell 2: 437–447. [PMC free article: PMC2435228] [PubMed: 18462694]
    59.
    St Laurent G. et al. (2012) Intronic RNAs constitute the major fraction of the non-coding RNA in mammalian cells. BMC Genomics 13: 504. [PMC free article: PMC3507791] [PubMed: 23006825]
    60.
    Espinoza C.A., Allen T.A., Hieb A.R., Kugel J.F. and Goodrich J.A. (2004) B2 RNA binds directly to RNA polymerase II to repress transcript synthesis. Nature Structural & Molecular Biology 11: 822–829. [PubMed: 15300239]
    61.
    Espinoza C.A., Goodrich J.A. and Kugel J.F. (2007) Characterization of the structure, function, and mechanism of B2 RNA, an ncRNA repressor of RNA polymerase II transcription. RNA 13: 583–596. [PMC free article: PMC1831867] [PubMed: 17307818]
    62.
    Mariner P.D. et al. (2008) Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Molecular Cell 29: 499–509. [PubMed: 18313387]
    63.
    Parrott A.M. and Mathews M.B. (2007) Novel rapidly evolving hominid RNAs bind nuclear factor 90 and display tissue-restricted distribution. Nucleic Acids Research 35: 6249–6258. [PMC free article: PMC2094060] [PubMed: 17855395]
    64.
    Parrott A.M. et al. (2011) The evolution and expression of the snaR family of small non-coding RNAs. Nucleic Acids Research 39: 1485–1500. [PMC free article: PMC3045588] [PubMed: 20935053]
    65.
    Conti A. et al. (2015) Identification of RNA polymerase III-transcribed Alu loci by computational screening of RNA-Seq data. Nucleic Acids Research 43: 817–835. [PMC free article: PMC4333407] [PubMed: 25550429]
    66.
    Stribling D. et al. (2021) A noncanonical microRNA derived from the snaR-A noncoding RNA targets a metastasis inhibitor. RNA 27: 694–709. [PMC free article: PMC8127991] [PubMed: 33795480]
    67.
    Van Bortle K. et al. (2021) A cancer-associated RNA polymerase III identity drives robust transcription and expression of SNAR-A noncoding RNA. bioRxiv: 2021.04.21.440535. [PMC free article: PMC9151912] [PubMed: 35637192]
    68.
    Lunyak V.V. et al. (2007) Developmentally regulated activation of a SINE B2 repeat as a domain boundary in organogenesis. Science 317: 248–251. [PubMed: 17626886]
    69.
    Dieci G., Fiorino G., Castelnuovo M., Teichmann M. and Pagano A. (2007) The expanding RNA polymerase III transcriptome. Trends in Genetics 23: 614–622. [PubMed: 17977614]
    70.
    Pagano A. et al. (2007) New small nuclear RNA gene-like transcriptional units as sources of regulatory transcripts. PLOS Genetics 3: e1. [PMC free article: PMC1790723] [PubMed: 17274687]
    71.
    White R.J. (2011) Transcription by RNA polymerase III: More complex than we thought. Nature Reviews Genetics 12: 459–463. [PubMed: 21540878]
    72.
    Djebali S. et al. (2012) Landscape of transcription in human cells. Nature 489: 101–108. [PMC free article: PMC3684276] [PubMed: 22955620]
    73.
    Fejes-Toth K. et al. (2009) Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature 457: 1028–1032. [PMC free article: PMC2719882] [PubMed: 19169241]
    74.
    Mercer T.R. et al. (2010) Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome. Genome Research 20: 1639–1650. [PMC free article: PMC2989990] [PubMed: 21045082]
    75.
    Mercer T.R. et al. (2011) Expression of distinct RNAs from 3′ untranslated regions. Nucleic Acids Research 39: 2393–2403. [PMC free article: PMC3064787] [PubMed: 21075793]
    76.
    Kapranov P. et al. (2010) The majority of total nuclear-encoded non-ribosomal RNA in a human cell is ‘dark matter’ un-annotated RNA. BMC Biology 8: 149. [PMC free article: PMC3022773] [PubMed: 21176148]
    77.
    Xu A.G. et al. (2010) Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq. PLOS Computational Biology 6: e1000843. [PMC free article: PMC2895644] [PubMed: 20617162]
    78.
    Yamada K. et al. (2003) Empirical analysis of transcriptional activity in the Arabidopsis genome. Science 302: 842–846. [PubMed: 14593172]
    79.
    Imanishi T. et al. (2004) Integrative annotation of 21,037 human genes validated by full-length cDNA clones. PLOS Biology 2: 856–875. [PMC free article: PMC393292] [PubMed: 15103394]
    80.
    Ota T. et al. (2004) Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature Genetics 36: 40–45. [PubMed: 14702039]
    81.
    Seki M. et al. (2004) RIKEN Arabidopsis full-length (RAFL) cDNA and its applications for expression profiling under abiotic stress conditions. Journal of Experimental Botany 55: 213–223. [PubMed: 14673034]
    82.
    Chen J. et al. (2002) Identifying novel transcripts and novel genes in the human genome by using novel SAGE tags. Proceedings of the National Academy of Sciences USA 99: 12257–12262. [PMC free article: PMC129432] [PubMed: 12213963]
    83.
    Saha S. et al. (2002) Using the transcriptome to annotate the genome. Nature Biotechnology 20: 508–512. [PubMed: 11981567]
    84.
    Meyers B.C. et al. (2004) Analysis of the transcriptional complexity of Arabidopsis thaliana by massively parallel signature sequencing. Nature Biotechnology 22: 1006–1011. [PubMed: 15247925]
    85.
    Jongeneel C.V. et al. (2005) An atlas of human gene expression from massively parallel signature sequencing. Genome Research 15: 1007–1014. [PMC free article: PMC1172045] [PubMed: 15998913]
    86.
    Schadt E.E. et al. (2004) A comprehensive transcript index of the human genome generated using microarrays and computational approaches. Genome Biology 5: R73. [PMC free article: PMC545593] [PubMed: 15461792]
    87.
    David L. et al. (2006) A high-resolution map of transcription in the yeast genome. Proceedings of the National Academy of Sciences USA 103: 5320–5325. [PMC free article: PMC1414796] [PubMed: 16569694]
    88.
    He H. et al. (2007) Mapping the C. elegans noncoding transcriptome with a whole-genome tiling microarray. Genome Research 17: 1471–1477. [PMC free article: PMC1987347] [PubMed: 17785534]
    89.
    Rinn J.L. et al. (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129: 1311–1323. [PMC free article: PMC2084369] [PubMed: 17604720]
    90.
    Stolc V. et al. (2004) A gene expression map for the euchromatic genome of Drosophila melanogaster. Science 306: 655–660. [PubMed: 15499012]
    91.
    Manak J.R. et al. (2006) Biological function of unannotated transcription during the early development of Drosophila melanogaster. Nature Genetics 38: 1151–1158. [PubMed: 16951679]
    92.
    Willingham A.T. et al. (2006) Transcriptional landscape of the human and fly genomes: Nonlinear and multifunctional modular model of transcriptomes. Cold Spring Harbor Symposia on Quantitative Biology 71: 101–110. [PubMed: 17480199]
    93.
    Roy S. et al. (2010) Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330: 1787–1797. [PMC free article: PMC3192495] [PubMed: 21177974]
    94.
    Cherbas L. et al. (2011) The transcriptional diversity of 25 Drosophila cell lines. Genome Research 21: 301–314. [PMC free article: PMC3032933] [PubMed: 21177962]
    95.
    Graveley B.R. et al. (2011) The developmental transcriptome of Drosophila melanogaster. Nature 471: 473–479. [PMC free article: PMC3075879] [PubMed: 21179090]
    96.
    Birney E. et al. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447: 799–816. [PMC free article: PMC2212820] [PubMed: 17571346]
    97.
    Mercer T.R., Dinger M.E. and Mattick J.S. (2009) Long noncoding RNAs: Insights into function. Nature Reviews Genetics 10: 155–159. [PubMed: 19188922]
    98.
    Sasaki Y.T. et al. (2007) Identification and characterization of human non-coding RNAs with tissue-specific expression. Biochemical and Biophysical Research Communications 357: 991–996. [PubMed: 17451645]
    99.
    Amaral P.P. and Mattick J.S. (2008) Noncoding RNA in development. Mammalian Genome 19: 454–492. [PubMed: 18839252]
    100.
    Furuno M. et al. (2006) Clusters of internally primed transcripts reveal novel long noncoding RNAs. PLOS Genetics 2: e37. [PMC free article: PMC1449886] [PubMed: 16683026]
    101.
    Hackermüller J. et al. (2014) Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein-coding RNAs. Genome Biology 15: R48. [PMC free article: PMC4054595] [PubMed: 24594072]
    102.
    Lazorthes S. et al. (2015) A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus. Nature Communications 6: 5971. [PMC free article: PMC4309439] [PubMed: 25601475]
    103.
    Sleutels F., Zwart R. and Barlow D.P. (2002) The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 415: 810–813. [PubMed: 11845212]
    104.
    Braidotti G. et al. (2004) The Air noncoding RNA: An imprinted cis-silencing transcript. Cold Spring Harbor Symposia on Quantitative Biology 69: 55–66. [PMC free article: PMC2847179] [PubMed: 16117633]
    105.
    Lorenzi L. et al. (2021) The RNA Atlas expands the catalog of human non-coding RNAs. Nature Biotechnology 39: 1453–1465. [PubMed: 34140680]
    106.
    Mendoza-Vargas A. et al. (2009) Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli. PLOS ONE 4: e7526. [PMC free article: PMC2760140] [PubMed: 19838305]
    107.
    Zhang G. et al. (2007) Antisense transcription in the human cytomegalovirus transcriptome. Journal of Virology 81: 11267–11281. [PMC free article: PMC2045512] [PubMed: 17686857]
    108.
    Manghera M., Magnusson A. and Douville R.N. (2017) The sense behind retroviral anti-sense transcription. Virology Journal 14: 9. [PMC free article: PMC5237517] [PubMed: 28088235]
    109.
    Liu G., Mattick J.S. and Taft R.J. (2013) A meta-analysis of the genomic and transcriptomic composition of complex life. Cell Cycle 12: 2061–2072. [PMC free article: PMC3737309] [PubMed: 23759593]
    110.
    Denoeud F. et al. (2007) Prominent use of distal 5′ transcription start sites and discovery of a large number of additional exons in ENCODE regions. Genome Research 17: 746–759. [PMC free article: PMC1891335] [PubMed: 17567994]
    111.
    Kapranov P. et al. (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316: 1484–1488. [PubMed: 17510325]
    112.
    St Laurent G. et al. (2013) VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer. Genome Biology 14: R73. [PMC free article: PMC4053963] [PubMed: 23876380]
    113.
    Faulkner G.J. et al. (2009) The regulated retrotransposon transcriptome of mammalian cells. Nature Genetics 41: 563–571. [PubMed: 19377475]
    114.
    Yeo G., Holste D., Kreiman G. and Burge C.B. (2004) Variation in alternative splicing across human tissues. Genome Biology 5: R74. [PMC free article: PMC545594] [PubMed: 15461793]
    115.
    Yeo G.W., Van Nostrand E., Holste D., Poggio T. and Burge C.B. (2005) Identification and analysis of alternative splicing events conserved in human and mouse. Proceedings of the National Academy of Sciences USA 102: 2850–2855. [PMC free article: PMC548664] [PubMed: 15708978]
    116.
    Wang E.T. et al. (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456: 470–476. [PMC free article: PMC2593745] [PubMed: 18978772]
    117.
    Pan Q., Shai O., Lee L.J., Frey B.J. and Blencowe B.J. (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nature Genetics 40: 1413–1415. [PubMed: 18978789]
    118.
    Raj B. and Blencowe B.J. (2015) Alternative splicing in the mammalian nervous system: Recent insights into mechanisms and functional roles. Neuron 87: 14–27. [PubMed: 26139367]
    119.
    Mercer T.R. et al. (2015) Genome-wide discovery of human splicing branchpoints. Genome Research 25: 290–303. [PMC free article: PMC4315302] [PubMed: 25561518]
    120.
    Tilgner H. et al. (2012) Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs. Genome Research 22: 1616–1625. [PMC free article: PMC3431479] [PubMed: 22955974]
    121.
    Mele M. et al. (2017) Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs. Genome Research 27: 27–37. [PMC free article: PMC5204342] [PubMed: 27927715]
    122.
    Mukherjee N. et al. (2017) Integrative classification of human coding and noncoding genes through RNA metabolism profiles. Nature Structural & Molecular Biology 24: 86–96. [PubMed: 27870833]
    123.
    Yin Y. et al. (2020) U1 snRNP regulates chromatin retention of noncoding RNAs. Nature 580: 147–150. [PubMed: 32238924]
    124.
    Kelley D. and Rinn J. (2012) Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biology 13: R107. [PMC free article: PMC3580499] [PubMed: 23181609]
    125.
    Kapusta A. et al. (2013) Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLOS Genetics 9: e1003470. [PMC free article: PMC3636048] [PubMed: 23637635]
    126.
    Johnson R. and Guigo R. (2014) The RIDL hypothesis: Transposable elements as functional domains of long noncoding RNAs. RNA 20: 959–976. [PMC free article: PMC4114693] [PubMed: 24850885]
    127.
    Fort A. et al. (2014) Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nature Genetics 46: 558–566. [PubMed: 24777452]
    128.
    Sasidharan R. and Gerstein M. (2008) Protein fossils live on as RNA. Nature 453: 729–731. [PubMed: 18528383]
    129.
    Li W., Yang W. and Wang X.-J. (2013) Pseudogenes: Pseudo or real functional elements? Journal of Genetics and Genomics 40: 171–177. [PubMed: 23618400]
    130.
    Cheetham S.W., Faulkner G.J. and Dinger M.E. (2020) Overcoming challenges and dogmas to understand the functions of pseudogenes. Nature Reviews Genetics 21: 191–201. [PubMed: 31848477]
    131.
    Ma Y. et al. (2021) Genome-wide analysis of pseudogenes reveals HBBP1′s human-specific essentiality in erythropoiesis and implication in β-thalassemia. Developmental Cell 56: 478–493. [PubMed: 33476555]
    132.
    Sanchez-Herrero E. and Akam M. (1989) Spatially ordered transcription of regulatory DNA in the bithorax complex of Drosophila. Development 107: 321–329. [PubMed: 2632227]
    133.
    Ashe H.L., Monks J., Wijgerde M., Fraser P. and Proudfoot N.J. (1997) Intergenic transcription and transinduction of the human beta-globin locus. Genes & Development 11: 2494–509. [PMC free article: PMC316561] [PubMed: 9334315]
    134.
    Feng J. et al. (2006) The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes & Development 20: 1470–1484. [PMC free article: PMC1475760] [PubMed: 16705037]
    135.
    Calin G.A. et al. (2007) Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 12: 215–229. [PubMed: 17785203]
    136.
    Amaral P.P. et al. (2009) Complex architecture and regulated expression of the Sox2ot locus during vertebrate development. RNA 15: 2013–2027. [PMC free article: PMC2764477] [PubMed: 19767420]
    137.
    Kim T.-K. et al. (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465: 182–187. [PMC free article: PMC3020079] [PubMed: 20393465]
    138.
    De Santa F. et al. (2010) A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLOS Biology 8: e1000384. [PMC free article: PMC2867938] [PubMed: 20485488]
    139.
    Wang D. et al. (2011) Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474: 390–394. [PMC free article: PMC3117022] [PubMed: 21572438]
    140.
    The Encode Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74. [PMC free article: PMC3439153] [PubMed: 22955616]
    141.
    Kim T.-K., Hemberg M. and Gray J.M. (2015) Enhancer RNAs: A class of long noncoding RNAs synthesized at enhancers. Cold Spring Harbor Perspectives in Biology 7: a018622. [PMC free article: PMC4292161] [PubMed: 25561718]
    142.
    Arnold P.R., Wells A.D. and Li X.C. (2020) Diversity and emerging roles of enhancer RNA in regulation of gene expression and cell fate. Frontiers in Cell and Developmental Biology 7: 377. [PMC free article: PMC6971116] [PubMed: 31993419]
    143.
    Jacquier A. (2009) The complex eukaryotic transcriptome: Unexpected pervasive transcription and novel small RNAs. Nature Reviews Genetics 10: 833–844. [PubMed: 19920851]
    144.
    Davis C.A. and Ares Jr. M., (2006) Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences USA 103: 3262–3267. [PMC free article: PMC1413877] [PubMed: 16484372]
    145.
    Preker P. et al. (2008) RNA exosome depletion reveals transcription upstream of active human promoters. Science 322: 1851–1854. [PubMed: 19056938]
    146.
    Taft R.J. et al. (2009) Tiny RNAs associated with transcription start sites in animals. Nature Genetics 41: 572–578. [PubMed: 19377478]
    147.
    Seila A.C. et al. (2008) Divergent transcription from active promoters. Science 322: 1849–1851. [PMC free article: PMC2692996] [PubMed: 19056940]
    148.
    Schmitz K.M., Mayer C., Postepska A. and Grummt I. (2010) Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes & Development 24: 2264–2269. [PMC free article: PMC2956204] [PubMed: 20952535]
    149.
    Mayer C., Schmitz K.M., Li J., Grummt I. and Santoro R. (2006) Intergenic transcripts regulate the epigenetic state of rRNA genes. Molecular Cell 22: 351–361. [PubMed: 16678107]
    150.
    Mayer C., Neubert M. and Grummt I. (2008) The structure of NoRC-associated RNA is crucial for targeting the chromatin remodelling complex NoRC to the nucleolus. EMBO Reports 9: 774–780. [PMC free article: PMC2515205] [PubMed: 18600236]
    151.
    Santoro R., Schmitz K.M., Sandoval J. and Grummt I. (2010) Intergenic transcripts originating from a subclass of ribosomal DNA repeats silence ribosomal RNA genes in trans. EMBO Reports 11: 52–58. [PMC free article: PMC2816622] [PubMed: 20010804]
    152.
    Memczak S. et al. (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495: 333–338. [PubMed: 23446348]
    153.
    Hansen T.B. et al. (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495: 384–388. [PubMed: 23446346]
    154.
    Kristensen L.S. et al. (2019) The biogenesis, biology and characterization of circular RNAs. Nature Reviews Genetics 20: 675–691. [PubMed: 31395983]
    155.
    Yin Q.-F. et al. (2012) Long noncoding RNAs with snoRNA ends. Molecular Cell 48: 219–230. [PubMed: 22959273]
    156.
    Ner-Gaon H. et al. (2004) Intron retention is a major phenomenon in alternative splicing in Arabidopsis. Plant Journal 39: 877–885. [PubMed: 15341630]
    157.
    Wong J.J.-L. et al. (2013) Orchestrated intron retention regulates normal granulocyte differentiation. Cell 154: 583–595. [PubMed: 23911323]
    158.
    Braunschweig U. et al. (2014) Widespread intron retention in mammals functionally tunes transcriptomes. Genome Research 24: 1774–1786. [PMC free article: PMC4216919] [PubMed: 25258385]
    159.
    Pimentel H. et al. (2015) A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis. Nucleic Acids Research 44: 838–851. [PMC free article: PMC4737145] [PubMed: 26531823]
    160.
    Schmitz U. et al. (2017) Intron retention enhances gene regulatory complexity in vertebrates. Genome Biology 18: 216. [PMC free article: PMC5688624] [PubMed: 29141666]
    161.
    Olthof A.M., Hyatt K.C. and Kanadia R.N. (2019) Minor intron splicing revisited: Identification of new minor intron-containing genes and tissue-dependent retention and alternative splicing of minor introns. BMC Genomics 20: 686. [PMC free article: PMC6717393] [PubMed: 31470809]
    162.
    Zeng C. and Hamada M. (2020) RNA-seq analysis reveals localization-associated alternative splicing across 13 cell lines. Genes 11: 820. [PMC free article: PMC7397181] [PubMed: 32708427]
    163.
    Dumbović G. et al. (2021) Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention. Nature Communications 12: 3308. [PMC free article: PMC8175569] [PubMed: 34083519]
    164.
    Flynn R.A. et al. (2021) Small RNAs are modified with N-glycans and displayed on the surface of living cells. Cell 184: 3109. [PMC free article: PMC9097497] [PubMed: 34004145]
    165.
    Huang N. et al. (2020) Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction. Genome Biology 21: 225. [PMC free article: PMC7488101] [PubMed: 32907628]
    166.
    Sharma C.M. et al. (2010) The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464: 250–255. [PubMed: 20164839]
    167.
    Puerta-Fernandez E., Barrick J.E., Roth A. and Breaker R.R. (2006) Identification of a large noncoding RNA in extremophilic eubacteria. Proceedings of the National Academy of Sciences USA 103: 19490–19495. [PMC free article: PMC1748253] [PubMed: 17164334]
    168.
    Ko J.-H. and Altman S. (2007) OLE RNA, an RNA motif that is highly conserved in several extremophilic bacteria, is a substrate for and can be regulated by RNase P RNA. Proceedings of the National Academy of Sciences USA 104: 7815–7820. [PMC free article: PMC1876530] [PubMed: 17470803]
    169.
    Weinberg Z., Perreault J., Meyer M.M. and Breaker R.R. (2009) Exceptional structured noncoding RNAs revealed by bacterial metagenome analysis. Nature 462: 656–659. [PMC free article: PMC4140389] [PubMed: 19956260]
    170.
    Harris K.A. and Breaker R.R. (2018) Large noncoding RNAs in bacteria. Microbiology Spectrum 6. doi:10.1128/microbiolspec.RWR-0005-2017. [PMC free article: PMC6042979] [PubMed: 29992899] [CrossRef]
    171.
    Frith M.C., Pheasant M. and Mattick J.S. (2005) The amazing complexity of the human transcriptome. European Journal of Human Genetics 13: 894–897. [PubMed: 15970949]
    172.
    Mattick J.S. and Makunin I.V. (2006) Non-coding RNA. Human Molecular Genetics 15: R17–29. [PubMed: 16651366]
    173.
    Kapranov P., Willingham A.T. and Gingeras T.R. (2007) Genome-wide transcription and the implications for genomic organization. Nature Reviews Genetics 8: 413–423. [PubMed: 17486121]
    174.
    Gingeras T.R. (2007) Origin of phenotypes: Genes and transcripts. Genome Research 17: 682–690. [PubMed: 17567989]
    175.
    Perez C.A.G. et al. (2021) Sense-overlapping lncRNA as a decoy of translational repressor protein for dimorphic gene expression. PLOS Genetics 17: e1009683. [PMC free article: PMC8351930] [PubMed: 34319983]
    176.
    Morris K.V. and Mattick J.S. (2014) The rise of regulatory RNA. Nature Reviews Genetics 15: 423–437. [PMC free article: PMC4314111] [PubMed: 24776770]
    177.
    Harrow J. et al. (2012) GENCODE: The reference human genome annotation for The ENCODE Project. Genome Research 22: 1760–1774. [PMC free article: PMC3431492] [PubMed: 22955987]
    178.
    Mattick J.S. (2003) Challenging the dogma: The hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 25: 930–939. [PubMed: 14505360]
    179.
    Dinger M.E., Amaral P.P., Mercer T.R. and Mattick J.S. (2009) Pervasive transcription of the eukaryotic genome: Functional indices and conceptual implications. Briefings in Functional Genomics and Proteomics 8: 407–423. [PubMed: 19770204]
    180.
    Amaral P.P., Dinger M.E., Mercer T.R. and Mattick J.S. (2008) The eukaryotic genome as an RNA machine. Science 319: 1787–1789. [PubMed: 18369136]
    181.
    Dinger M.E., Pang K.C., Mercer T.R. and Mattick J.S. (2008) Differentiating protein-coding and noncoding RNA: Challenges and ambiguities. PLOS Computational Biology 4: e1000176. [PMC free article: PMC2518207] [PubMed: 19043537]
    182.
    Galindo M.I., Pueyo J.I., Fouix S., Bishop S.A. and Couso J.P. (2007) Peptides encoded by short ORFs control development and define a new eukaryotic gene family. PLOS Biology 5: e106. [PMC free article: PMC1852585] [PubMed: 17439302]
    183.
    Gultyaev A.P. and Roussis A. (2007) Identification of conserved secondary structures and expansion segments in enod40 RNAs reveals new enod40 homologues in plants. Nucleic Acids Research 35: 3144–3152. [PMC free article: PMC1888808] [PubMed: 17452360]
    184.
    Hanyu-Nakamura K., Sonobe-Nojima H., Tanigawa A., Lasko P. and Nakamura A. (2008) Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells. Nature 451: 730–733. [PMC free article: PMC2719856] [PubMed: 18200011]
    185.
    Cabili M.N. et al. (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes & Development 25: 1915–1927. [PMC free article: PMC3185964] [PubMed: 21890647]
    186.
    Gascoigne D.K. et al. (2012) Pinstripe: A suite of programs for integrating transcriptomic and proteomic datasets identifies novel proteins and improves differentiation of protein-coding and non-coding genes. Bioinformatics 28: 3042–3050. [PubMed: 23044541]
    187.
    Frith M.C. et al. (2006) The abundance of short proteins in the mammalian proteome. PLOS Genetics 2: e52. [PMC free article: PMC1449894] [PubMed: 16683031]
    188.
    Magny E.G. et al. (2013) Conserved regulation of cardiac calcium uptake by peptides encoded in small open reading frames. Science 341: 1116–1120. [PubMed: 23970561]
    189.
    Lauressergues D. et al. (2015) Primary transcripts of microRNAs encode regulatory peptides. Nature 520: 90–93. [PubMed: 25807486]
    190.
    Anderson D.M. et al. (2015) A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160: 595–606. [PMC free article: PMC4356254] [PubMed: 25640239]
    191.
    Matsumoto A. et al. (2017) mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature 541: 228–232. [PubMed: 28024296]
    192.
    Stein C.S. et al. (2018) Mitoregulin: A lncRNA-encoded microprotein that supports mitochondrial supercomplexes and respiratory efficiency. Cell Reports 23: 3710–3720. [PMC free article: PMC6091870] [PubMed: 29949756]
    193.
    Ransohoff J.D., Wei Y. and Khavari P.A. (2018) The functions and unique features of long intergenic non-coding RNA. Nature Reviews Molecular Cell Biology 19: 143–157. [PMC free article: PMC5889127] [PubMed: 29138516]
    194.
    Lewandowski J.P. et al. (2020) The Tug1 lncRNA locus is essential for male fertility. Genome Biology 21: 237. [PMC free article: PMC7487648] [PubMed: 32894169]
    195.
    Chen J. et al. (2020) Pervasive functional translation of noncanonical human open reading frames. Science 367: 1140–1146. [PMC free article: PMC7289059] [PubMed: 32139545]
    196.
    Eckhart L., Lachner J., Tschachler E. and Rice R.H. (2020) TINCR is not a non-coding RNA but encodes a protein component of cornified epidermal keratinocytes. Experimental Dermatology 29: 376–379. [PMC free article: PMC7187231] [PubMed: 32012357]
    197.
    Nita A. et al. (2021) A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing. PLOS Genetics 17: e1009686. [PMC free article: PMC8341662] [PubMed: 34351912]
    198.
    Guttman M., Russell P., Ingolia N.T., Weissman J.S. and Lander E.S. (2013) Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell 154: 240–251. [PMC free article: PMC3756563] [PubMed: 23810193]
    199.
    Röhrig H., Schmidt J., Miklashevichs E., Schell J. and John M. (2002) Soybean ENOD40 encodes two peptides that bind to sucrose synthase. Proceedings of the National Academy of Sciences USA 99: 1915–1920. [PMC free article: PMC122294] [PubMed: 11842184]
    200.
    Dinger M.E., Gascoigne D.K. and Mattick J.S. (2011) The evolution of RNAs with multiple functions. Biochimie 93: 2013–2018. [PubMed: 21802485]
    201.
    Candeias M.M. et al. (2008) p53 mRNA controls p53 activity by managing Mdm2 functions. Nature Cell Biology 10: 1098–1105. [PubMed: 19160491]
    202.
    Cooper C. et al. (2011) Steroid receptor RNA activator bi-faceted genetic system: Heads or Tails? Biochimie 93: 1973–1980. [PubMed: 21771633]
    203.
    Kumari P. and Sampath K. (2015) cncRNAs: Bi-functional RNAs with protein coding and non-coding functions. Seminars in Cell & Developmental Biology 47–48: 40–51. [PMC free article: PMC4683094] [PubMed: 26498036]
    204.
    Gilot D. et al. (2017) A non-coding function of TYRP1 mRNA promotes melanoma growth. Nature Cell Biology 19: 1348–1357. [PubMed: 28991221]
    205.
    Ivanyi-Nagy R. et al. (2018) The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis. eLife 7: e40037. [PMC free article: PMC6249008] [PubMed: 30355447]
    206.
    Crerar H. et al. (2019) Regulation of NGF signaling by an axonal untranslated mRNA. Neuron 102: 553–563. [PMC free article: PMC6509357] [PubMed: 30853298]
    207.
    Gaertner B. et al. (2020) A human ESC-based screen identifies a role for the translated lncRNA LINC00261 in pancreatic endocrine differentiation. eLife 9: e58659. [PMC free article: PMC7423336] [PubMed: 32744504]
    208.
    Prasad A., Sharma N. and Prasad M. (2021) Noncoding but coding: Pri-miRNA into the action. Trends in Plant Science 26: 204–206. [PubMed: 33353820]
    209.
    Broadwell L.J. et al. (2021) Myosin 7b is a regulatory long noncoding RNA (lncMYH7b) in the human heart. Journal of Biological Chemistry 296: 100694. [PMC free article: PMC8141895] [PubMed: 33895132]
    210.
    Boraas L. et al. (2021) Non-coding function for mRNAs in focal adhesion architecture and mechanotransduction. bioRxiv: 2021.10.04.463097.
    211.
    Lecuyer E. et al. (2007) Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell 131: 174–187. [PubMed: 17923096]
    212.
    Ryder P.V. and Lerit D.A. (2018) RNA localization regulates diverse and dynamic cellular processes. Traffic 19: 496–502. [PMC free article: PMC6003861] [PubMed: 29653028]
    213.
    Grelet S. et al. (2017) A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression. Nature Cell Biology 19: 1105–1115. [PMC free article: PMC5578890] [PubMed: 28825698]
    214.
    Hube F. et al. (2006) Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines. DNA and Cell Biology 25: 418–428. [PubMed: 16848684]
    215.
    Leygue E. (2007) Steroid receptor RNA activator (SRA1): Unusual bifaceted gene products with suspected relevance to breast cancer. Nuclear Receptor Signaling 5: e006. [PMC free article: PMC1948073] [PubMed: 17710122]
    216.
    Hashimoto K. et al. (2009) A liver X receptor (LXR)-β alternative splicing variant (LXRBSV) acts as an RNA co-activator of LXR-β. Biochemical and Biophysical Research Communications 390: 1260–1265. [PubMed: 19878653]
    217.
    Ulveling D., Francastel C. and Hube F. (2011) When one is better than two: RNA with dual functions. Biochimie 93: 633–644. [PubMed: 21111023]
    218.
    Ulveling D., Francastel C. and Hube F. (2011) Identification of potentially new bifunctional RNA based on genome-wide data-mining of alternative splicing events. Biochimie 93: 2024–2027. [PubMed: 21729736]
    219.
    Williamson L. et al. (2017) UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene. Cell 168: 843–855. [PMC free article: PMC5332558] [PubMed: 28215706]
    220.
    Gautron A. et al. (2021) Human TYRP1: Two functions for a single gene? Pigment Cell & Melanoma Research 34: 836–852. [PubMed: 33305505]
    221.
    Qu S. et al. (2021) PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity. Genome Biology 22: 104. [PMC free article: PMC8042710] [PubMed: 33849634]
    222.
    Gonzàlez-Porta M., Frankish A., Rung J., Harrow J. and Brazma A. (2013) Transcriptome analysis of human tissues and cell lines reveals one dominant transcript per gene. Genome Biology 14: R70. [PMC free article: PMC4053754] [PubMed: 23815980]
    223.
    Duret L., Chureau C., Samain S., Weissenbach J. and Avner P. (2006) The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science 312: 1653–1655. [PubMed: 16778056]
    224.
    Elisaphenko E.A. et al. (2008) A dual origin of the Xist gene from a protein-coding gene and a set of transposable elements. PLOS ONE 3: e2521. [PMC free article: PMC2430539] [PubMed: 18575625]
    225.
    Hezroni H. et al. (2017) A subset of conserved mammalian long non-coding RNAs are fossils of ancestral protein-coding genes. Genome Biology 18: 162. [PMC free article: PMC5577775] [PubMed: 28854954]
    226.
    Beck-Engeser G.B. et al. (2008) Pvt1-encoded microRNAs in oncogenesis. Retrovirology 5: 4. [PMC free article: PMC2257975] [PubMed: 18194563]
    227.
    He D. et al. (2021) miRNA-independent function of long noncoding pri-miRNA loci. Proceedings of the National Academy of Sciences USA 118: e2017562118. [PMC free article: PMC8020771] [PubMed: 33758101]
    228.
    Immarigeon C. et al. (2021) Identification of a micropeptide and multiple secondary cell genes that modulate Drosophila male reproductive success. Proceedings of the National Academy of Sciences USA 118: e2001897118. [PMC free article: PMC8053986] [PubMed: 33876742]
    229.
    Montigny A. et al. (2021) Drosophila primary microRNA-8 encodes a microRNA-encoded peptide acting in parallel of miR-8. Genome Biology 22: 118. [PMC free article: PMC8063413] [PubMed: 33892772]
    230.
    Yang T. et al. (2017) lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression. Oncotarget 8: 85353–85367. [PMC free article: PMC5689614] [PubMed: 29156724]
    231.
    Holdt L.M. and Teupser D. (2018) Long noncoding RNA ANRIL: Lnc-ing genetic variation at the chromosome 9p21 locus to molecular mechanisms of atherosclerosis. Frontiers in Cardiovascular Medicine 5: 145. [PMC free article: PMC6232298] [PubMed: 30460243]
    232.
    Hubberten M. et al. (2019) Linear isoforms of the long noncoding RNA CDKN2B-AS1 regulate the c-myc-enhancer binding factor RBMS1. European Journal of Human Genetics 27: 80–89. [PMC free article: PMC6303254] [PubMed: 30108282]
    233.
    Ghetti M., Vannini I., Storlazzi C.T., Martinelli G. and Simonetti G. (2020) Linear and circular PVT1 in hematological malignancies and immune response: Two faces of the same coin. Molecular Cancer 19: 69. [PMC free article: PMC7104523] [PubMed: 32228602]
    234.
    Shuai T. et al. (2021) lncRNA TRMP-S directs dual mechanisms to regulate p27-mediated cellular senescence. Molecular Therapy - Nucleic Acids 24: 971–985. [PMC free article: PMC8141606] [PubMed: 34094715]
    235.
    Wanowska E., Kubiak M., Makałowska I. and Szcześniak M.W. (2021) A chromatin-associated splicing isoform of OIP5-AS1 acts in cis to regulate the OIP5 oncogene. RNA Biology 18: 1834–1845. [PMC free article: PMC8582974] [PubMed: 33404283]
    236.
    Dennis C. (2002) The brave new world of RNA. Nature 418: 122–124. [PubMed: 12110860]
    237.
    Jarvis K. and Robertson M. (2011) The noncoding universe. BMC Biology 9: 52. [PMC free article: PMC3145610] [PubMed: 21798102]
    238.
    Babak T., Blencowe B.J. and Hughes T.R. (2005) A systematic search for new mammalian noncoding RNAs indicates little conserved intergenic transcription. BMC Genomics 6: 104. [PMC free article: PMC1199595] [PubMed: 16083503]
    239.
    van Bakel H., Nislow C., Blencowe B.J. and Hughes T.R. (2010) Most “dark matter” transcripts are associated with known genes. PLOS Biology 8: e1000371. [PMC free article: PMC2872640] [PubMed: 20502517]
    240.
    Palazzo A.F. and Lee E.S. (2015) Non-coding RNA: What is functional and what is junk? Frontiers in Genetics 6: 2. [PMC free article: PMC4306305] [PubMed: 25674102]
    241.
    Lloréns-Rico V. et al. (2016) Bacterial antisense RNAs are mainly the product of transcriptional noise. Science Advances 2: e1501363. [PMC free article: PMC4783119] [PubMed: 26973873]
    242.
    Elowitz M.B., Levine A.J., Siggia E.D. and Swain P.S. (2002) Stochastic gene expression in a single cell. Science 297: 1183–1186. [PubMed: 12183631]
    243.
    Raser J.M. and O‘Shea E.K. (2005) Noise in gene expression: Origins, consequences, and control. Science 309: 2010–2013. [PMC free article: PMC1360161] [PubMed: 16179466]
    244.
    Blake W.J. M. K.A., Cantor C.R. and Collins J.J. (2003) Noise in eukaryotic gene expression. Nature 422: 633–7. [PubMed: 12687005]
    245.
    Arias A.M. and Hayward P. (2006) Filtering transcriptional noise during development: concepts and mechanisms. Nature Reviews Genetics 7: 34–44. [PubMed: 16369570]
    246.
    Ramsey S. et al. (2006) Transcriptional noise and cellular heterogeneity in mammalian macrophages. Philosophical Transactions of the Royal Society B: Biological Sciences 361: 495–506. [PMC free article: PMC1609340] [PubMed: 16524838]
    247.
    Struhl K. (2007) Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nature Structural & Molecular Biology 14: 103–105. [PubMed: 17277804]
    248.
    Clark M.B. et al. (2011) The reality of pervasive transcription. PLOS Biology 9: e1000625. [PMC free article: PMC3134446] [PubMed: 21765801]
    249.
    van Bakel H., Nislow C., Blencowe B.J. and Hughes T.R. (2011) Response to “the reality of pervasive transcription”. PLOS Biology 9: e1001102.
    250.
    Graur D. et al. (2013) On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of encode. Genome Biology and Evolution 5: 578–590. [PMC free article: PMC3622293] [PubMed: 23431001]
    251.
    Mattick J.S. and Dinger M.E. (2013) The extent of functionality in the human genome. HUGO Journal 7: 2.
    252.
    Mercer T.R. et al. (2012) Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nature Biotechnology 30: 99–104. [PMC free article: PMC3710462] [PubMed: 22081020]
    253.
    Clark M.B. et al. (2015) Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing. Nature Methods 12: 339–342. [PubMed: 25751143]
    254.
    Gloss B.S. and Dinger M.E. (2016) The specificity of long noncoding RNA expression. Biochimica et Biophysica Acta 1859: 16–22. [PubMed: 26297315]
    255.
    Xu Q. et al. (2017) Systematic comparison of lncRNAs with protein coding mRNAs in population expression and their response to environmental change. BMC Plant Biology 17: 42. [PMC free article: PMC5307861] [PubMed: 28193161]
    256.
    Sharova L.V. et al. (2009) Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells. DNA Research 16: 45–58. [PMC free article: PMC2644350] [PubMed: 19001483]
    257.
    Clark M. et al. (2012) Genome-wide analysis of long noncoding RNA stability. Genome Research 21: 885–898. [PMC free article: PMC3337434] [PubMed: 22406755]
    258.
    Field A.R. et al. (2019) Structurally conserved primate lncRNAs are transiently expressed during human cortical differentiation and influence cell-type-specific genes. Stem Cell Reports 12: 245–257. [PMC free article: PMC6372947] [PubMed: 30639214]
    259.
    Houseley J., Rubbi L., Grunstein M., Tollervey D. and Vogelauer M. (2008) A ncRNA modulates histone modification and mRNA induction in the yeast GAL gene cluster. Molecular Cell 32: 685–695. [PMC free article: PMC7610895] [PubMed: 19061643]
    260.
    Wang K.C. et al. (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472: 120–124. [PMC free article: PMC3670758] [PubMed: 21423168]
    261.
    Li Z. et al. (2013) The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. Proceedings of the National Academy of Sciences USA 111: 1002–1007. [PMC free article: PMC3903238] [PubMed: 24371310]
    262.
    Li M.A. et al. (2017) A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation. eLife 6: e23468. [PMC free article: PMC5562443] [PubMed: 28820723]
    263.
    Xing Y.-H. et al. (2017) SLERT regulates DDX21 rings associated with Pol I transcription. Cell 169: 664–678. [PubMed: 28475895]
    264.
    Seiler J. et al. (2017) The lncRNA VELUCT strongly regulates viability of lung cancer cells despite its extremely low abundance. Nucleic Acids Research 45: 5458–5469. [PMC free article: PMC5435915] [PubMed: 28160600]
    265.
    Hao Q. et al. (2020) The S-phase-induced lncRNA SUNO1 promotes cell proliferation by controlling YAP1/Hippo signaling pathway. eLife 9: e55102. [PMC free article: PMC7591261] [PubMed: 33108271]
    266.
    Rowland T.J., Dumbović G., Hass E.P., Rinn J.L. and Cech T.R. (2019) Single-cell imaging reveals unexpected heterogeneity of telomerase reverse transcriptase expression across human cancer cell lines. Proceedings of the National Academy of Sciences USA 116: 18488–18497. [PMC free article: PMC6744858] [PubMed: 31451652]
    267.
    Mitchell P., Petfalski E., Shevchenko A., Mann M. and Tollervey D. (1997) The exosome: A conserved eukaryotic RNA processing complex containing multiple 3′-->5′ exoribonucleases. Cell 91: 457–466. [PubMed: 9390555]
    268.
    Mitchell P. and Tollervey D. (2000) Musing on the structural organization of the exosome complex. Nature Structural Biology 7: 843–846. [PubMed: 11017189]
    269.
    Houseley J., LaCava J. and Tollervey D. (2006) RNA-quality control by the exosome. Nature Reviews Molecular Cell Biology 7: 529–539. [PubMed: 16829983]
    270.
    Losson R. and Lacroute F. (1979) Interference of nonsense mutations with eukaryotic messenger RNA stability. Proceedings of the National Academy of Sciences USA 76: 5134–5137. [PMC free article: PMC413094] [PubMed: 388431]
    271.
    Nagy E. and Maquat L.E. (1998) A rule for termination-codon position within intron-containing genes: When nonsense affects RNA abundance. Trends in Biochemical Sciences 23: 198–199. [PubMed: 9644970]
    272.
    Conti E. and Izaurralde E. (2005) Nonsense-mediated mRNA decay: Molecular insights and mechanistic variations across species. Current Opinion in Cell Biology 17: 316–325. [PubMed: 15901503]
    273.
    Behm-Ansmant I. et al. (2007) mRNA quality control: An ancient machinery recognizes and degrades mRNAs with nonsense codons. FEBS Letters 581: 2845–2853. [PubMed: 17531985]
    274.
    Isken O. and Maquat L.E. (2007) Quality control of eukaryotic mRNA: Safeguarding cells from abnormal mRNA function. Genes & Development 21: 1833–1856. [PubMed: 17671086]
    275.
    Kurihara Y. et al. (2009) Genome-wide suppression of aberrant mRNA-like noncoding RNAs by NMD in Arabidopsis. Proceedings of the National Academy of Sciences USA 106: 2453–2458. [PMC free article: PMC2650177] [PubMed: 19181858]
    276.
    Boehm V. and Gehring N.H. (2016) Exon junction complexes: Supervising the gene expression assembly line. Trends in Genetics 32: 724–735. [PubMed: 27667727]
    277.
    Isken O. and Maquat L.E. (2008) The multiple lives of NMD factors: Balancing roles in gene and genome regulation. Nature Reviews Genetics 9: 699–712. [PMC free article: PMC3711694] [PubMed: 18679436]
    278.
    Neu-Yilik G. and Kulozik A.E. (2008) NMD: Multitasking between mRNA surveillance and modulation of gene expression. Advances in Genetics 62: 185–243. [PubMed: 19010255]
    279.
    Karam R., Wengrod J., Gardner L.B. and Wilkinson M.F. (2013) Regulation of nonsense-mediated mRNA decay: Implications for physiology and disease. Biochimica et Biophysica Acta 1829: 624–633. [PMC free article: PMC3660545] [PubMed: 23500037]
    280.
    Andjus S., Morillon A. and Wery M. (2021) From yeast to mammals, the nonsense-mediated mRNA decay as a master regulator of long non-coding RNAs functional trajectory. Non-Coding RNA 7: 44. [PMC free article: PMC8395947] [PubMed: 34449682]
    281.
    Karam R. et al. (2015) The unfolded protein response is shaped by the NMD pathway. EMBO Reports 16: 599–609. [PMC free article: PMC4428047] [PubMed: 25807986]
    282.
    Huang L. and Wilkinson M.F. (2012) Regulation of nonsense-mediated mRNA decay. WIREs RNA 3: 807–828. [PubMed: 23027648]
    283.
    Li T. et al. (2015) Smg6/Est1 licenses embryonic stem cell differentiation via nonsense-mediated mRNA decay. EMBO Journal 34: 1630–1647. [PMC free article: PMC4475398] [PubMed: 25770585]
    284.
    Lou C.-H. et al. (2016) Nonsense-mediated RNA decay influences human embryonic stem cell fate. Stem Cell Reports 6: 844–857. [PMC free article: PMC4912386] [PubMed: 27304915]
    285.
    Jaffrey S.R. and Wilkinson M.F. (2018) Nonsense-mediated RNA decay in the brain: Emerging modulator of neural development and disease. Nature Reviews Neuroscience 19: 715–728. [PMC free article: PMC6396682] [PubMed: 30410025]
    286.
    Wyers F. et al. (2005) Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121: 725–737. [PubMed: 15935759]
    287.
    Thompson D.M. and Parker R. (2007) Cytoplasmic decay of intergenic transcripts in Saccharomyces cerevisiae. Molecular and Cellular Biology 27: 92–101. [PMC free article: PMC1800667] [PubMed: 17074811]
    288.
    Chekanova J.A. et al. (2007) Genome-wide high-resolution mapping of exosome substrates reveals hidden features in the Arabidopsis transcriptome. Cell 131: 1340–1353. [PubMed: 18160042]
    289.
    Camblong J., Iglesias N., Fickentscher C., Dieppois G. and Stutz F. (2007) Antisense RNA stabilization induces transcriptional gene silencing via histone deacetylation in S. cerevisiae. Cell 131: 706–717. [PubMed: 18022365]
    290.
    Houseley J., Kotovic K., El Hage A. and Tollervey D. (2007) Trf4 targets ncRNAs from telomeric and rDNA spacer regions and functions in rDNA copy number control. EMBO Journal 26: 4996–5006. [PMC free article: PMC2080816] [PubMed: 18007593]
    291.
    Uhler J.P., Hertel C. and Svejstrup J.Q. (2007) A role for noncoding transcription in activation of the yeast PHO5 gene. Proceedings of the National Academy of Sciences USA 104: 8011–8016. [PMC free article: PMC1859995] [PubMed: 17470801]
    292.
    Vasiljeva L., Kim M., Terzi N., Soares L.M. and Buratowski S. (2008) Transcription termination and RNA degradation contribute to silencing of RNA polymerase II transcription within heterochromatin. Molecular Cell 29: 313–323. [PubMed: 18280237]
    293.
    Berretta J., Pinskaya M. and Morillon A. (2008) A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae. Genes & Development 22: 615–626. [PMC free article: PMC2259031] [PubMed: 18316478]
    294.
    Toesca I., Nery C.R., Fernandez C.F., Sayani S. and Chanfreau G.F. (2011) Cryptic transcription mediates repression of subtelomeric metal homeostasis genes. PLOS Genetics 7: e1002163. [PMC free article: PMC3128112] [PubMed: 21738494]
    295.
    Yin S. et al. (2020) The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum. RNA Biology 17: 828–842. [PMC free article: PMC7549624] [PubMed: 32079470]
    296.
    Balarezo-Cisneros L.N. et al. (2021) Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and in trans effects on the protein regulatory network. PLOS Genetics 17: e1008761. [PMC free article: PMC7886133] [PubMed: 33493158]
    297.
    Andersson R. et al. (2014) An atlas of active enhancers across human cell types and tissues. Nature 507: 455–461. [PMC free article: PMC5215096] [PubMed: 24670763]
    298.
    Pefanis E. et al. (2015) RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell 161: 774–789. [PMC free article: PMC4428671] [PubMed: 25957685]
    299.
    Sone M. et al. (2007) The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons. Journal of Cell Science 120: 2498–2506. [PubMed: 17623775]
    300.
    Mercer T.R., Dinger M.E., Sunkin S.M., Mehler M.F. and Mattick J.S. (2008) Specific expression of long noncoding RNAs in the mouse brain. Proceedings of the National Academy of Sciences USA 105: 716–1712. [PMC free article: PMC2206602] [PubMed: 18184812]
    301.
    Goff L.A. et al. (2015) Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain. Proceedings of the National Academy of Sciences USA 112: 6855–6862. [PMC free article: PMC4460505] [PubMed: 26034286]
    302.
    Bocchi V.D. et al. (2021) The coding and long noncoding single-cell atlas of the developing human fetal striatum. Science 372: eabf5759. [PubMed: 33958447]
    303.
    Pauli A. et al. (2012) Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis. Genome Research 22: 577–591. [PMC free article: PMC3290793] [PubMed: 22110045]
    304.
    Inagaki S. et al. (2005) Identification and expression analysis of putative mRNA-like non-coding RNA in Drosophila. Genes to Cells 10: 1163–1173. [PubMed: 16324153]
    305.
    Tupy J.L. et al. (2005) Identification of putative noncoding polyadenylated transcripts in Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 102: 5495–5500. [PMC free article: PMC555963] [PubMed: 15809421]
    306.
    Sawata M. et al. (2002) Identification and punctate nuclear localization of a novel noncoding RNA, Ks-1, from the honeybee brain. RNA 8: 772–785. [PMC free article: PMC1370296] [PubMed: 12088150]
    307.
    Sawata M., Takeuchi H. and Kubo T. (2004) Identification and analysis of the minimal promoter activity of a novel noncoding nuclear RNA gene, AncR-1, from the honeybee (Apis mellifera L.). RNA 10: 1047–1058. [PMC free article: PMC1370596] [PubMed: 15208441]
    308.
    Wang M. et al. (2021) Sex-specific development in haplodiploid honeybee is controlled by the female-embryo-specific activation of thousands of intronic lncRNAs. Frontiers in Cell and Developmental Biology 9: 690167. [PMC free article: PMC8377728] [PubMed: 34422813]
    309.
    Gribnau J., Diderich K., Pruzina S., Calzolari R. and Fraser P. (2000) Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus. Molecular Cell 5: 377–386. [PubMed: 10882078]
    310.
    Chen H., Du G., Song X. and Li L. (2017) Non-coding transcripts from enhancers: New insights into enhancer activity and gene expression regulation. Genomics, Proteomics & Bioinformatics 15: 201–207. [PMC free article: PMC5487526] [PubMed: 28599852]
    311.
    Ivaldi M.S. et al. (2018) Fetal γ-globin genes are regulated by the BGLT3 long noncoding RNA locus. Blood 132: 1963–1973. [PMC free article: PMC6213316] [PubMed: 30150205]
    312.
    Rogan D.F. et al. (2004) Analysis of intergenic transcription in the human IL-4/IL-13 gene cluster. Proceedings of the National Academy of Sciences USA 101: 2446–2451. [PMC free article: PMC356970] [PubMed: 14983029]
    313.
    Jones E.A. and Flavell R.A. (2005) Distal enhancer elements transcribe intergenic RNA in the IL-10 family gene cluster. Journal of Immunology 175: 7437–7446. [PubMed: 16301651]
    314.
    Islam S. et al. (2011) Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. Genome Research 21: 1160–1167. [PMC free article: PMC3129258] [PubMed: 21543516]
    315.
    Kim Daniel H. et al. (2015) Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression during reprogramming. Cell Stem Cell 16: 88–101. [PMC free article: PMC4291542] [PubMed: 25575081]
    316.
    Liu S.J. et al. (2016) Single-cell analysis of long non-coding RNAs in the developing human neocortex. Genome Biology 17: 67. [PMC free article: PMC4831157] [PubMed: 27081004]
    317.
    Lencer E., Prekeris R. and Artinger K.B. (2021) Single-cell RNA analysis identifies pre-migratory neural crest cells expressing markers of differentiated derivatives. eLife 10: e66078. [PMC free article: PMC8367380] [PubMed: 34397384]
    318.
    Isakova A., Neff N. and Quake S.R. (2021) Single-cell quantification of a broad RNA spectrum reveals unique noncoding patterns associated with cell types and states. Proceedings of the National Academy of Sciences USA 118: e2113568118. [PMC free article: PMC8713755] [PubMed: 34911763]
    319.
    Brena C., Chipman A.D., Minelli A. and Akam M. (2006) Expression of trunk Hox genes in the centipede Strigamia maritima: Sense and anti-sense transcripts. Evolution & Development 8: 252–265. [PubMed: 16686636]
    320.
    Deveson I.W. et al. (2016) Representing genetic variation with synthetic DNA standards. Nature Methods 13: 784–791. [PubMed: 27502217]
    321.
    Hardwick S.A. et al. (2016) Spliced synthetic genes as internal controls in RNA sequencing experiments. Nature Methods 13: 792–798. [PubMed: 27502218]
    322.
    Wong T., Deveson I.W., Hardwick S.A. and Mercer T.R. (2017) ANAQUIN: A software toolkit for the analysis of spike-in controls for next generation sequencing. Bioinformatics 33: 1723–1724. [PubMed: 28130232]
    323.
    Blackburn J. et al. (2019) Use of synthetic DNA spike-in controls (sequins) for human genome sequencing. Nature Protocols 14: 2119–2151. [PubMed: 31217595]
    324.
    Deveson I.W. et al. (2019) Chiral DNA sequences as commutable controls for clinical genomics. Nature Communications 10: 1342. [PMC free article: PMC6430799] [PubMed: 30902988]
    325.
    Hardwick S.A. et al. (2018) Synthetic microbe communities provide internal reference standards for metagenome sequencing and analysis. Nature Communications 9: 3096. [PMC free article: PMC6078961] [PubMed: 30082706]
    326.
    Mercer T.R. et al. (2014) Targeted sequencing for gene discovery and quantification using RNA CaptureSeq. Nature Protocols 9: 989–1009. [PubMed: 24705597]
    327.
    Bussotti G. et al. (2016) Improved definition of the mouse transcriptome via targeted RNA sequencing. Genome Research 26: 705–716. [PMC free article: PMC4864457] [PubMed: 27197243]
    328.
    Lagarde J. et al. (2017) High-throughput annotation of full-length long noncoding RNAs with capture long-read sequencing. Nature Genetics 49: 1731–1740. [PMC free article: PMC5709232] [PubMed: 29106417]
    329.
    Bartonicek N. et al. (2017) Intergenic disease-associated regions are abundant in novel transcripts. Genome Biology 18: 241. [PMC free article: PMC5747244] [PubMed: 29284497]
    330.
    Hardwick S.A. et al. (2019) Targeted, high-resolution RNA sequencing of non-coding genomic regions associated with neuropsychiatric functions. Frontiers in Genetics 10: 309. [PMC free article: PMC6473190] [PubMed: 31031799]
    331.
    de Goede O.M. et al. (2021) Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease. Cell 184: 2633–2648. [PMC free article: PMC8651477] [PubMed: 33864768]
    332.
    Hon C.-C. et al. (2017) An atlas of human long non-coding RNAs with accurate 5′ ends. Nature 543: 199–204. [PMC free article: PMC6857182] [PubMed: 28241135]
    333.
    Nasser J. et al. (2021) Genome-wide enhancer maps link risk variants to disease genes. Nature 593: 238–243. [PMC free article: PMC9153265] [PubMed: 33828297]
    334.
    Eze U.C., Bhaduri A., Haeussler M., Nowakowski T.J. and Kriegstein A.R. (2021) Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia. Nature Neuroscience 24: 584–594. [PMC free article: PMC8012207] [PubMed: 33723434]
    335.
    Orom U.A. et al. (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143: 46–58. [PMC free article: PMC4108080] [PubMed: 20887892]
    336.
    Derrien T. et al. (2012) The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Research 22: 1775–1789. [PMC free article: PMC3431493] [PubMed: 22955988]
    337.
    Unfried J.P. et al. (2019) Identification of coding and long noncoding RNAs differentially expressed in tumors and preferentially expressed in healthy tissues. Cancer Research 79: 5167–5180. [PubMed: 31387921]
    338.
    Lein E.S. et al. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445: 168–176. [PubMed: 17151600]
    339.
    Sunkin S.M. and Hohmann J.G. (2007) Insights from spatially mapped gene expression in the mouse brain. Human Molecular Genetics 16: R209–19. [PubMed: 17911164]
    340.
    Gaiti F. et al. (2015) Dynamic and widespread lncRNA expression in a sponge and the origin of animal complexity. Molecular Biology and Evolution 32: 2367–2382. [PMC free article: PMC4540969] [PubMed: 25976353]
    341.
    Dinger M.E. et al. (2008) Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Research 18: 1433–1445. [PMC free article: PMC2527704] [PubMed: 18562676]
    342.
    Sheik Mohamed J., Gaughwin P.M., Lim B., Robson P. and Lipovich L. (2010) Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 16: 324–337. [PMC free article: PMC2811662] [PubMed: 20026622]
    343.
    Kohtz J.D. and Fishell G. (2004) Developmental regulation of EVF-1, a novel non-coding RNA transcribed upstream of the mouse Dlx6 gene. Gene Expression Patterns 4: 407–412. [PubMed: 15183307]
    344.
    Johnson R. et al. (2009) Regulation of neural macroRNAs by the transcriptional repressor REST. RNA 15: 85–96. [PMC free article: PMC2612765] [PubMed: 19050060]
    345.
    Mercer T.R. et al. (2010) Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation. BMC Neuroscience 11: 14. [PMC free article: PMC2829031] [PubMed: 20137068]
    346.
    Sunwoo H. et al. (2009) MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Research 19: 347–359. [PMC free article: PMC2661813] [PubMed: 19106332]
    347.
    Askarian-Amiri M.E. et al. (2011) SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA 17: 878–891. [PMC free article: PMC3078737] [PubMed: 21460236]
    348.
    Pang K.C. et al. (2009) Genome-wide identification of long noncoding RNAs in CD8+ T cells. Journal of Immunology 182: 7738–7748. [PubMed: 19494298]
    349.
    Zhang X. et al. (2009) A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster. Blood 113: 2526–2534. [PMC free article: PMC2656274] [PubMed: 19144990]
    350.
    Dinger M.E. et al. (2009) NRED: A database of long noncoding RNA expression. Nucleic Acids Research 37: D122–6. [PMC free article: PMC2686506] [PubMed: 18829717]
    351.
    Warren W.C. et al. (2010) The genome of a songbird. Nature 464: 757–762. [PMC free article: PMC3187626] [PubMed: 20360741]
    352.
    Amaral P.P., Dinger M.E. and Mattick J.S. (2013) Non-coding RNAs in homeostasis, disease and stress responses: An evolutionary perspective. Briefings in Functional Genomics 12: 254–278. [PubMed: 23709461]
    353.
    Bhatia G., Sharma S., Upadhyay S.K. and Singh K. (2019) Long non-coding RNAs coordinate developmental transitions and other key biological processes in grapevine. Scientific Reports 9: 3552. [PMC free article: PMC6401051] [PubMed: 30837504]
    354.
    Yu Y., Zhang Y., Chen X. and Chen Y. (2019) Plant noncoding RNAs: Hidden players in development and stress responses. Annual Review of Cell and Developmental Biology 35: 407–431. [PMC free article: PMC8034839] [PubMed: 31403819]
    355.
    Kim W., Miguel-Rojas C., Wang J., Townsend J.P. and Trail F. (2018) Developmental dynamics of long noncoding RNA expression during sexual fruiting body formation in Fusarium graminearum. mBio 9: e01292. [PMC free article: PMC6094484] [PubMed: 30108170]
    356.
    Tiedge H., Fremeau Jr. R.T., Weinstock P.H., Arancio O. and Brosius J. (1991) Dendritic location of neural BC1 RNA. Proceedings of the National Academy of Sciences USA 88: 2093–2097. [PMC free article: PMC51175] [PubMed: 1706516]
    357.
    Shimada T., Yamashita A. and Yamamoto M. (2003) The fission yeast meiotic regulator Mei2p forms a dot structure in the horse-tail nucleus in association with the sme2 locus on chromosome II. Molecular Biology of the Cell 14: 2461–2469. [PMC free article: PMC194894] [PubMed: 12808043]
    358.
    Hutchinson J.N. et al. (2007) A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics 8: 39. [PMC free article: PMC1800850] [PubMed: 17270048]
    359.
    Clemson C.M. et al. (2009) An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Molecular Cell 33: 717–726. [PMC free article: PMC2696186] [PubMed: 19217333]
    360.
    Clark M.B. and Mattick J.S. (2011) Long noncoding RNAs in cell biology. Seminars in Cell & Developmental Biology 22: 366–376. [PubMed: 21256239]
    361.
    Carrieri C. et al. (2012) Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491: 454–457. [PubMed: 23064229]
    362.
    Cabili M.N. et al. (2015) Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution. Genome Biology 16: 20. [PMC free article: PMC4369099] [PubMed: 25630241]
    363.
    Wilk R., Hu J., Blotsky D. and Krause H.M. (2016) Diverse and pervasive subcellular distributions for both coding and long noncoding RNAs. Genes & Development 30: 594–609. [PMC free article: PMC4782052] [PubMed: 26944682]
    364.
    Chen L.-L. (2016) Linking long noncoding RNA localization and function. Trends in Biochemical Sciences 41: 761–772. [PubMed: 27499234]
    365.
    Mas-Ponte D. et al. (2017) LncATLAS database for subcellular localization of long noncoding RNAs. RNA 23: 1080–1087. [PMC free article: PMC5473142] [PubMed: 28386015]
    366.
    Wen X. et al. (2018) lncSLdb: A resource for long non-coding RNA subcellular localization. Database 2018: bay085. [PMC free article: PMC6146130] [PubMed: 30219837]
    367.
    Benoit Bouvrette L.P. et al. (2018) CeFra-seq reveals broad asymmetric mRNA and noncoding RNA distribution profiles in Drosophila and human cells. RNA 24: 98–113. [PMC free article: PMC5733575] [PubMed: 29079635]
    368.
    Palazzo A.F. and Lee E.S. (2018) Sequence determinants for nuclear retention and cytoplasmic export of mRNAs and lncRNAs. Frontiers in Genetics 9: 440. [PMC free article: PMC6199362] [PubMed: 30386371]
    369.
    Zhao Y. et al. (2019) Aberrant shuttling of long noncoding RNAs during the mitochondria-nuclear crosstalk in hepatocellular carcinoma cells. American Journal of Cancer Research 9: 999–1008. [PMC free article: PMC6556595] [PubMed: 31218107]
    370.
    Miao H. et al. (2019) A long noncoding RNA distributed in both nucleus and cytoplasm operates in the PYCARD-regulated apoptosis by coordinating the epigenetic and translational regulation. PLOS Genetics 15: e1008144. [PMC free article: PMC6534332] [PubMed: 31086376]
    371.
    Guo C.-J. et al. (2020) Distinct processing of lncRNAs contributes to non-conserved functions in stem cells. Cell 181: 621–636. [PubMed: 32259487]
    372.
    Bridges M.C., Daulagala A.C. and Kourtidis A. (2021) LNCcation: lncRNA localization and function. Journal of Cell Biology 220: e202009045. [PMC free article: PMC7816648] [PubMed: 33464299]
    373.
    Tani H. et al. (2012) Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals. Genome Research 22: 947–956. [PMC free article: PMC3337439] [PubMed: 22369889]
    374.
    Shi K., Liu T., Fu H., Li W. and Zheng X. (2021) Genome-wide analysis of lncRNA stability in human. PLOS Computational Biology 17: e1008918. [PMC free article: PMC8081339] [PubMed: 33861746]
    375.
    Mattick J.S. (2009) The gene377. Cawley Stic signatures of noncoding RNAs. PLOS Genetics 5: e1000459. [PMC free article: PMC2667263] [PubMed: 19390609]
    376.
    Martone R. et al. (2003) Distribution of NF-kappaB-binding sites across human chromosome 22. Proceedings of the National Academy of Sciences USA 100: 12247–12252. [PMC free article: PMC218744] [PubMed: 14527995]
    377.
    Cawley S. et al. (2004) Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116: 499–509. [PubMed: 14980218]
    378.
    Euskirchen G. et al. (2004) CREB binds to multiple loci on human chromosome 22. Molecular Cell Biology 24: 3804–3814. [PMC free article: PMC387762] [PubMed: 15082775]
    379.
    Kim T.H. et al. (2005) A high-resolution map of active promoters in the human genome. Nature 436: 876–880. [PMC free article: PMC1895599] [PubMed: 15988478]
    380.
    Odom D.T. et al. (2006) Core transcriptional regulatory circuitry in human hepatocytes. Molecular Systems Biology 2: 2006.0017. [PMC free article: PMC1681491] [PubMed: 16738562]
    381.
    Louro R. et al. (2007) Androgen responsive intronic non-coding RNAs. BMC Biology 5: 4. [PMC free article: PMC1800835] [PubMed: 17263875]
    382.
    Louro R., Smirnova A.S. and Verjovski-Almeida S. (2009) Long intronic noncoding RNA transcription: Expression noise or expression choice? Genomics 93: 291–298. [PubMed: 19071207]
    383.
    Lopez F., Granjeaud S., Ara T., Ghattas B. and Gautheret D. (2006) The disparate nature of “intergenic” polyadenylation sites. RNA 12: 1794–1801. [PMC free article: PMC1581981] [PubMed: 16931874]
    384.
    Ponjavic J., Ponting C.P. and Lunter G. (2007) Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Research 17: 556–565. [PMC free article: PMC1855172] [PubMed: 17387145]
    385.
    Guttman M. et al. (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458: 223–227. [PMC free article: PMC2754849] [PubMed: 19182780]
    386.
    Smith M.A., Gesell T., Stadler P.F. and Mattick J.S. (2013) Widespread purifying selection on RNA structure in mammals. Nucleic Acids Research 41: 8220–8236. [PMC free article: PMC3783177] [PubMed: 23847102]
    387.
    Hiller M. et al. (2009) Conserved introns reveal novel transcripts in Drosophila melanogaster. Genome Research 19: 1289–300. [PMC free article: PMC2704441] [PubMed: 19458021]
    388.
    Will S., Yu M. and Berger B. (2013) Structure-based whole genome realignment reveals many novel non-coding RNAs. Genome Research 6: 1018–1027. [PMC free article: PMC3668356] [PubMed: 23296921]
    389.
    Nitsche A., Rose D., Fasold M., Reiche K. and Stadler P.F. (2015) Comparison of splice sites reveals that long noncoding RNAs are evolutionarily well conserved. RNA 21: 801–812. [PMC free article: PMC4408788] [PubMed: 25802408]
    390.
    Vancura A. et al. (2021) Cancer LncRNA Census 2 (CLC2): An enhanced resource reveals clinical features of cancer lncRNAs. NAR Cancer 3: zcab013. [PMC free article: PMC8210278] [PubMed: 34316704]
    391.
    Chodroff R.A. et al. (2010) Long noncoding RNA genes: Conservation of sequence and brain expression among diverse amniotes. Genome Biology 11: R72. [PMC free article: PMC2926783] [PubMed: 20624288]
    392.
    Hezroni H. et al. (2015) Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Reports 11: 1110–1122. [PMC free article: PMC4576741] [PubMed: 25959816]
    393.
    Amaral P.P. et al. (2018) Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci. Genome Biology 19: 32. [PMC free article: PMC5853149] [PubMed: 29540241]
    394.
    Washietl S., Hofacker I.L., Lukasser M., Huttenhofer A. and Stadler P.F. (2005) Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome. Nature Biotechnology 23: 1383–1390. [PubMed: 16273071]
    395.
    Torarinsson E., Sawera M., Havgaard J.H., Fredholm M. and Gorodkin J. (2006) Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. Genome Research 16: 885–889. [PMC free article: PMC1484455] [PubMed: 16751343]
    396.
    Torarinsson E. et al. (2008) Comparative genomics beyond sequence-based alignments: RNA structures in the ENCODE regions. Genome Research 18: 242–251. [PMC free article: PMC2203622] [PubMed: 18096747]
    397.
    Vandivier L.E., Anderson S.J., Foley S.W. and Gregory B.D. (2016) The conservation and function of RNA secondary structure in plants. Annual Review of Plant Biology 67: 463–488. [PMC free article: PMC5125251] [PubMed: 26865341]
    398.
    Delli Ponti R., Armaos A., Marti S. and Tartaglia G.G. (2018) A method for RNA structure prediction shows evidence for structure in lncRNAs. Frontiers in Molecular Biosciences 5: 111. [PMC free article: PMC6286970] [PubMed: 30560136]
    399.
    Steigele S., Huber W., Stocsits C., Stadler P.F. and Nieselt K. (2007) Comparative analysis of structured RNAs in S. cerevisiae indicates a multitude of different functions. BMC Biology 5: 25. [PMC free article: PMC1914338] [PubMed: 17577407]
    400.
    Jung C.H., Makunin I.V. and Mattick J.S. (2010) Identification of conserved Drosophila-specific euchromatin-restricted non-coding sequence motifs. Genomics 96: 154–166. [PubMed: 20595017]
    401.
    Ross C.J. et al. (2021) Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences. Genome Biology 22: 29. [PMC free article: PMC7798263] [PubMed: 33430943]
    402.
    Pang K.C., Frith M.C. and Mattick J.S. (2006) Rapid evolution of noncoding RNAs: Lack of conservation does not mean lack of function. Trends in Genetics 22: 1–5. [PubMed: 16290135]
    403.
    Quinn J.J. et al. (2016) Rapid evolutionary turnover underlies conserved lncRNA-genome interactions. Genes & Development 30: 191–207. [PMC free article: PMC4719309] [PubMed: 26773003]
    404.
    Karner H. et al. (2020) Functional conservation of lncRNA JPX despite sequence and structural divergence. Journal of Molecular Biology 432: 283–300. [PubMed: 31518612]
    405.
    Oh H.J. and Lee J.T. (2020) Long noncoding RNA functionality beyond sequence: The Jpx model. Journal of Molecular Biology 432: 301–304. [PubMed: 31892474]
    406.
    Lyle R. et al. (2000) The imprinted antisense RNA at the Igf2r locus overlaps but does not imprint Mas1. Nature Genetics 25: 19–21. [PubMed: 10802648]
    407.
    Millar J.K. et al. (2000) Disruption of two novel genes by a translocation co-segregating with schizophrenia. Human Molecular Genetics 9: 1415–1423. [PubMed: 10814723]
    408.
    Liu A.Y., Torchia B.S., Migeon B.R. and Siliciano R.F. (1997) The human NTT gene: Identification of a novel 17-kb noncoding nuclear RNA expressed in activated CD4+ T cells. Genomics 39: 171–184. [PubMed: 9027504]
    409.
    Takeda K. et al. (1998) Identification of a novel bone morphogenetic protein-responsive gene that may function as a noncoding RNA. Journal of Biological Chemistry 273: 17079–17085. [PubMed: 9642273]
    410.
    Michel U., Kallmann B., Rieckmann P. and Isbrandt D. (2002) UM 9(5)h and UM 9(5)p, human and porcine noncoding transcripts with preferential expression in the cerebellum. RNA 8: 1538–1547. [PMC free article: PMC1370359] [PubMed: 12515386]
    411.
    Ulitsky I., Shkumatava A., Jan C.H., Sive H. and Bartel D.P. (2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147: 1537–1550. [PMC free article: PMC3376356] [PubMed: 22196729]
    412.
    Pheasant M. and Mattick J.S. (2007) Raising the estimate of functional human sequences. Genome Research 17: 1245–1253. [PubMed: 17690206]
    413.
    Smith N.G., Brandstrom M. and Ellegren H. (2004) Evidence for turnover of functional noncoding DNA in mammalian genome evolution. Genomics 84: 806–813. [PubMed: 15475259]
    414.
    Kutter C. et al. (2012) Rapid turnover of long noncoding RNAs and the evolution of gene expression. PLOS Genetics 8: e1002841. [PMC free article: PMC3406015] [PubMed: 22844254]
    415.
    Dai H. et al. (2008) The evolution of courtship behaviors through the origination of a new gene in Drosophila. Proceedings of the National Academy of Sciences USA 105: 7478–7483. [PMC free article: PMC2396706] [PubMed: 18508971]
    416.
    Paralkar V.R. et al. (2014) Lineage and species-specific long noncoding RNAs during erythro-megakaryocytic development. Blood 123: 1927–1937. [PMC free article: PMC3962165] [PubMed: 24497530]
    417.
    de Almeida R.A., Fraczek M.G., Parker S., Delneri D. and O‘Keefe R.T. (2016) Non-coding RNAs and disease: The classical ncRNAs make a comeback. Biochemical Society Transactions 44: 1073–1078. [PMC free article: PMC6042638] [PubMed: 27528754]
    418.
    Sulisalo T. et al. (1993) Cartilage-hair hypoplasia gene assigned to chromosome 9 by linkage analysis. Nature Genetics 3: 338–341. [PubMed: 7981754]
    419.
    Ridanpää M. et al. (2001) Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell 104: 195–203. [PubMed: 11207361]
    420.
    Rogler L.E. et al. (2014) Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage-hair hypoplasia. Human Molecular Genetics 23: 368–382. [PMC free article: PMC3869355] [PubMed: 24009312]
    421.
    Huang W. et al. (2015) DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature 528: 517–522. [PMC free article: PMC4762670] [PubMed: 26675721]
    422.
    Chen Y. et al. (2021) Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP. Proceedings of the National Academy of Sciences USA 118: e2026813118. [PMC free article: PMC8307289] [PubMed: 34266953]
    423.
    Murdock D.R. et al. (2021) Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing. Journal of Clinical Investigation 131: e141500. [PMC free article: PMC7773386] [PubMed: 33001864]
    424.
    Stenson P.D. et al. (2017) The human gene mutation database: Towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Human Genetics 136: 665–677. [PMC free article: PMC5429360] [PubMed: 28349240]
    425.
    Broadbent H.M. et al. (2007) Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked, SNPs in the ANRIL locus on chromosome 9p. Human Molecular Genetics 17: 806–814. [PubMed: 18048406]
    426.
    Pasmant E., Sabbagh A., Vidaud M. and Bièche I. (2010) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB Journal 25: 444–448. [PubMed: 20956613]
    427.
    Tan J.Y. et al. (2017) Cis-acting complex-trait-associated lincRNA expression correlates with modulation of chromosomal architecture. Cell Reports 18: 2280–2288. [PubMed: 28249171]
    428.
    Zhang D.-D. et al. (2017) Long noncoding RNA LINC00305 promotes inflammation by activating the AHRR-NF-κB pathway in human monocytes. Scientific Reports 7: 46204. [PMC free article: PMC5385552] [PubMed: 28393844]
    429.
    Cho H. et al. (2019) Long noncoding RNA ANRIL regulates endothelial cell activities associated with coronary artery disease by up-regulating CLIP1, EZR, and LYVE1 genes. Journal of Biological Chemistry 294: 3881–3898. [PMC free article: PMC6422082] [PubMed: 30655286]
    430.
    Allou L. et al. (2021) Non-coding deletions identify Maenli lncRNA as a limb-specific En1 regulator. Nature 592: 93–98. [PubMed: 33568816]
    431.
    Seifuddin F. et al. (2020) lncRNAKB, a knowledgebase of tissue-specific functional annotation and trait association of long noncoding RNA. Scientific Data 7: 326. [PMC free article: PMC7536183] [PubMed: 33020484]
    432.
    Asgari Y., Heng J.I.T., Lovell N., Forrest A.R.R. and Alinejad-Rokny H. (2020) Evidence for enhancer noncoding RNAs (enhancer-ncRNAs) with gene regulatory functions relevant to neurodevelopmental disorders. bioRxiv: 2020.05.16.087395v2.
    433.
    Kelley R.L. et al. (1999) Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Cell 98: 513–522. [PubMed: 10481915]
    434.
    Meller V.H. and Rattner B.P. (2002) The roX genes encode redundant male-specific lethal transcripts required for targeting of the MSL complex. EMBO Journal 21: 1084–1091. [PMC free article: PMC125901] [PubMed: 11867536]
    435.
    Georges M., Charlier C. and Cockett N. (2003) The callipyge locus: Evidence for the trans interaction of reciprocally imprinted genes. Trends in Genetics 19: 248–252. [PubMed: 12711215]
    436.
    Davis E. et al. (2005) RNAi-mediated allelic trans-Interaction at the imprinted Rtl1/Peg11 locus. Current Biology 15: 743–749. [PubMed: 15854907]
    437.
    Takeda H. et al. (2006) The callipyge mutation enhances bidirectional long-range DLK1-GTL2 intergenic transcription in cis. Proceedings of the National Academy of Sciences USA 103: 8119–8124. [PMC free article: PMC1472439] [PubMed: 16690740]
    438.
    Mikovic J. et al. (2018) MicroRNA and long non-coding RNA regulation in skeletal muscle from growth to old age shows striking dysregulation of the callipyge locus. Frontiers in Genetics 9: 548. [PMC free article: PMC6250799] [PubMed: 30505320]
    439.
    Van Laere A.S. et al. (2003) A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig. Nature 425: 832–836. [PubMed: 14574411]
    440.
    Li J. et al. (2021) The crest phenotype in domestic chicken is caused by a 197 bp duplication in the intron of HOXC10. G3 (Genes, Genomes, Genetics) 11: jkaa048. [PMC free article: PMC8022956] [PubMed: 33704432]
    441.
    Alberti C. and Cochella L. (2017) A framework for understanding the roles of miRNAs in animal development. Development 144: 2548–2559. [PubMed: 28720652]
    442.
    Miska E.A. et al. (2007) Most Caenorhabditis elegans microRNAs are individually not essential for development or viability. PLOS Genetics 3: e215. [PMC free article: PMC2134938] [PubMed: 18085825]
    443.
    Soshnev A.A. et al. (2011) A conserved long noncoding RNA affects sleep behavior in Drosophila. Genetics 189: 455–468. [PMC free article: PMC3189806] [PubMed: 21775470]
    444.
    Jenny A. et al. (2006) A translation-independent role of oskar RNA in early Drosophila oogenesis. Development 133: 2827–2833. [PubMed: 16835436]
    445.
    Kenny A., Morgan M.B. and Macdonald P.M. (2021) Different roles for the adjoining and structurally similar A-rich and poly(A) domains of oskar mRNA: Only the A-rich domain is required for oskar noncoding RNA function, which includes MTOC positioning. Developmental Biology 476: 117–127. [PMC free article: PMC8186867] [PubMed: 33798537]
    446.
    Taft R.J., Pang K.C., Mercer T.R., Dinger M. and Mattick J.S. (2009) Non-coding RNAs: Regulators of disease. Journal of Pathology 220: 126–139. [PubMed: 19882673]
    447.
    Wapinski O. and Chang H.Y. (2011) Long noncoding RNAs and human disease. Trends in Cell Biology 21: 354–361. [PubMed: 21550244]
    448.
    Wan P., Su W. and Zhuo Y. (2017) The role of long noncoding RNAs in neurodegenerative diseases. Molecular Neurobiology 54: 2012–2021. [PubMed: 26910817]
    449.
    Wanowska E., Kubiak M.R., Rosikiewicz W., Makałowska I. and Szcześniak M.W. (2018) Natural antisense transcripts in diseases: From modes of action to targeted therapies. Wiley Interdisciplinary Reviews RNA 9: e1461. [PMC free article: PMC5838512] [PubMed: 29341438]
    450.
    Aznaourova M., Schmerer N., Schmeck B. and Schulte L.N. (2020) Disease-causing mutations and rearrangements in long non-coding RNA gene loci. Frontiers in Genetics 11: 527484. [PMC free article: PMC7735109] [PubMed: 33329688]
    451.
    Rom A. et al. (2019) Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability. Nature Communications 10: 5092. [PMC free article: PMC6841665] [PubMed: 31704914]
    452.
    Sutherland H.F. et al. (1996) Identification of a novel transcript disrupted by a balanced translocation associated with DiGeorge syndrome. American Journal of Human Genetics 59: 23–31. [PMC free article: PMC1915101] [PubMed: 8659529]
    453.
    Abe Y. et al. (2014) Xq26.1–26.2 gain identified on array comparative genomic hybridization in bilateral periventricular nodular heterotopia with overlying polymicrogyria. Developmental Medicine & Child Neurology 56: 1221–1224. [PubMed: 25052774]
    454.
    Ang C.E. et al. (2019) The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders. eLife 8: e41770. [PMC free article: PMC6380841] [PubMed: 30628890]
    455.
    Long H.K. et al. (2020) Loss of extreme long-range enhancers in human neural crest drives a craniofacial disorder. Cell Stem Cell 27: 765–783. [PMC free article: PMC7655526] [PubMed: 32991838]
    456.
    Maass P.G. et al. (2012) A misplaced lncRNA causes brachydactyly in humans. Journal of Clinical Investigation 122: 3990–4002. [PMC free article: PMC3485082] [PubMed: 23093776]
    457.
    Shepherdson J.L., Zheng H., Amarillo I.E., McAlinden A. and Shinawi M. (2021) Delineation of the 1q24.3 microdeletion syndrome provides further evidence for the potential role of non-coding RNAs in regulating the skeletal phenotype. Bone 142: 115705. [PMC free article: PMC8020873] [PubMed: 33141070]
    458.
    Yu T.-T. et al. (2021) Deletion at an 1q24 locus reveals a critical role of long noncoding RNA DNM3OS in skeletal development. Cell & Bioscience 11: 47. [PMC free article: PMC7923828] [PubMed: 33653390]
    459.
    Meng L. et al. (2015) Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature 518: 409–412. [PMC free article: PMC4351819] [PubMed: 25470045]
    460.
    Rougeulle C., Cardoso C., Fontes M., Colleaux L. and Lalande M. (1998) An imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript. Nature Genetics 19: 15–16. [PubMed: 9590281]
    461.
    Jong M.T. et al. (1999) A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region. Human Molecular Genetics 8: 783–793. [PubMed: 10196367]
    462.
    Royo H. et al. (2007) Bsr, a nuclear-retained RNA with monoallelic expression. Molecular Biology of the Cell 18: 2817–2827. [PMC free article: PMC1949380] [PubMed: 17507654]
    463.
    Vitali P., Royo H., Marty V., Bortolin-Cavaille M.L. and Cavaille J. (2010) Long nuclear-retained non-coding RNAs and allele-specific higher-order chromatin organization at imprinted snoRNA gene arrays. Journal of Cell Science 123: 70–83. [PubMed: 20016068]
    464.
    Polesskaya O.O., Haroutunian V., Davis K.L., Hernandez I. and Sokolov B.P. (2003) Novel putative nonprotein-coding RNA gene from 11q14 displays decreased expression in brains of patients with schizophrenia. Journal of Neuroscience Research 74: 111–122. [PubMed: 13130513]
    465.
    Barry G. et al. (2014) The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Molecular Psychiatry 19: 486–494. [PubMed: 23628989]
    466.
    Ip J.Y. et al. (2016) Gomafu lncRNA knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine. Scientific Reports 6: 27204. [PMC free article: PMC4890022] [PubMed: 27251103]
    467.
    Stamou M. et al. (2020) A balanced translocation in Kallmann syndrome implicates a long noncoding RNA, RMST, as a GnRH neuronal regulator. Journal of Clinical Endocrinology & Metabolism 105: e231–44. [PMC free article: PMC7112981] [PubMed: 31628846]
    468.
    Chillambhi S. et al. (2010) Deletion of the noncoding GNAS Antisense transcript causes pseudohypoparathyroidism type ib and biparental defects of GNAS methylation in cis. Journal of Clinical Endocrinology & Metabolism 95: 3993–4002. [PMC free article: PMC2913043] [PubMed: 20444925]
    469.
    Bohnsack J.P., Teppen T., Kyzar E.J., Dzitoyeva S. and Pandey S.C. (2019) The lncRNA BDNF-AS is an epigenetic regulator in the human amygdala in early onset alcohol use disorders. Translational Psychiatry 9: 34. [PMC free article: PMC6365546] [PubMed: 30728347]
    470.
    Ruan X. et al. (2021) Identification of human long noncoding RNAs associated with nonalcoholic fatty liver disease and metabolic homeostasis. Journal of Clinical investigation 131: e136336. [PMC free article: PMC7773374] [PubMed: 33048844]
    471.
    Zemmour D., Pratama A., Loughhead S.M., Mathis D. and Benoist C. (2017) Flicr, a long noncoding RNA, modulates Foxp3 expression and autoimmunity. Proceedings of the National Academy of Sciences USA 114: E3472–80. [PMC free article: PMC5410798] [PubMed: 28396406]
    472.
    Zhang F., Liu G., Wei C., Gao C. and Hao J. (2017) Linc-MAF-4 regulates Th1/Th2 differentiation and is associated with the pathogenesis of multiple sclerosis by targeting MAF. FASEB Journal 31: 519–525. [PubMed: 27756768]
    473.
    Shirasawa S. et al. (2004) SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease. Human Molecular Genetics 13: 2221–2231. [PubMed: 15294872]
    474.
    Wang J. et al. (2016) Upregulation of long noncoding RNA TMEVPG1 enhances T helper type 1 cell response in patients with Sjögren syndrome. Immunologic Research 64: 489–496. [PubMed: 26440590]
    475.
    Castellanos-Rubio A. et al. (2016) A long noncoding RNA associated with susceptibility to celiac disease. Science 352: 91–95. [PMC free article: PMC4994711] [PubMed: 27034373]
    476.
    Kotzin J.J. et al. (2016) The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan. Nature 537: 239–243. [PMC free article: PMC5161578] [PubMed: 27525555]
    477.
    Sonkoly E. et al. (2005) Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS. Journal of Biological Chemistry 280: 24159–24167. [PubMed: 15855153]
    478.
    Széll M., Danis J., Bata-Csörgő Z. and Kemény L. (2016) PRINS, a primate-specific long non-coding RNA, plays a role in the keratinocyte stress response and psoriasis pathogenesis. European Journal of Physiology 468: 935–943. [PMC free article: PMC4893059] [PubMed: 26935426]
    479.
    Padua D. et al. (2016) A long noncoding RNA signature for ulcerative colitis identifies IFNG-AS1 as an enhancer of inflammation. American Journal of Physiology-Gastrointestinal and Liver Physiology 311: G446–G57. [PMC free article: PMC5076004] [PubMed: 27492330]
    480.
    Hu Y.-W. et al. (2019) Long noncoding RNA NEXN-AS1 mitigates atherosclerosis by regulating the actin-binding protein NEXN. Journal of Clinical Investigation 129: 1115–1128. [PMC free article: PMC6391138] [PubMed: 30589415]
    481.
    Ou M., Li X., Zhao S., Cui S. and Tu J. (2020) Long non-coding RNA CDKN2B-AS1 contributes to atherosclerotic plaque formation by forming RNA-DNA triplex in the CDKN2B promoter. EBioMedicine 55: 102694. [PMC free article: PMC7184162] [PubMed: 32335370]
    482.
    Han P. et al. (2014) A long noncoding RNA protects the heart from pathological hypertrophy. Nature 514: 102–106. [PMC free article: PMC4184960] [PubMed: 25119045]
    483.
    Faghihi M.A. et al. (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nature Medicine 14: 723–730. [PMC free article: PMC2826895] [PubMed: 18587408]
    484.
    Mutsuddi M., Marshall C.M., Benzow K.A., Koob M.D. and Rebay I. (2004) The spinocerebellar ataxia 8 noncoding RNA causes neurodegeneration and associates with staufen in Drosophila. Current Biology 14: 302–308. [PubMed: 14972680]
    485.
    Sopher B.L. et al. (2011) CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA. Neuron 70: 1071–1084. [PMC free article: PMC3139428] [PubMed: 21689595]
    486.
    Ishii N. et al. (2006) Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. Journal of Human Genetics 51: 1087–1099. [PubMed: 17066261]
    487.
    Tufarelli C. et al. (2003) Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nature Genetics 34: 157–165. [PubMed: 12730694]
    488.
    Giannopoulou E. et al. (2012) A single nucleotide polymorphism in the HbbP1 gene in the human β-globin locus is associated with a mild β-thalassemia disease phenotype. Hemoglobin 36: 433–445. [PubMed: 22943111]
    489.
    Li Y. et al. (2021) A noncoding RNA modulator potentiates phenylalanine metabolism in mice. Science 373: 662–673. [PMC free article: PMC9714245] [PubMed: 34353949]
    490.
    He F. et al. (2019) Integrative analysis of somatic mutations in non-coding regions altering RNA secondary structures in cancer genomes. Scientific Reports 9: 8205. [PMC free article: PMC6546760] [PubMed: 31160636]
    491.
    Huarte M. (2015) The emerging role of lncRNAs in cancer. Nature Medicine 21: 1253–1261. [PubMed: 26540387]
    492.
    Wang Z. et al. (2018) lncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic lncRNA that interacts with MYC and promotes cell-cycle progression in cancer. Cancer Cell 33: 706–720. [PMC free article: PMC6143179] [PubMed: 29622465]
    493.
    Jiang M.-C., Ni J.-J., Cui W.-Y., Wang B.-Y. and Zhuo W. (2019) Emerging roles of lncRNA in cancer and therapeutic opportunities. American Journal of Cancer Research 9: 1354–1366. [PMC free article: PMC6682721] [PubMed: 31392074]
    494.
    Carlevaro-Fita J. et al. (2020) Cancer LncRNA census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis. Communications Biology 3: 56. [PMC free article: PMC7002399] [PubMed: 32024996]
    495.
    Guo F., Li L., Yang W., Hu J.-F. and Cui J. (2021) Long noncoding RNA: A resident staff of genomic instability regulation in tumorigenesis. Cancer Letters 503: 103–109. [PubMed: 33516792]
    496.
    Liu S.J., Dang H.X., Lim D.A., Feng F.Y. and Maher C.A. (2021) Long noncoding RNAs in cancer metastasis. Nature Reviews Cancer 21: 446–460. [PMC free article: PMC8288800] [PubMed: 33953369]
    497.
    Landskron L. et al. (2018) The asymmetrically segregating lncRNA cherub is required for transforming stem cells into malignant cells. eLife 7: e31347. [PMC free article: PMC5871330] [PubMed: 29580384]
    498.
    Young T.L., Matsuda T. and Cepko C.L. (2005) The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Current Biology 15: 501–512. [PubMed: 15797018]
    499.
    Ji P. et al. (2003) MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22: 6087–6097. [PubMed: 12970751]
    500.
    Berteaux N. et al. (2005) H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. Journal of Biological Chemistry 280: 29625–29636. [PubMed: 15985428]
    501.
    Reis E.M. et al. (2005) Large-scale transcriptome analyses reveal new genetic marker candidates of head, neck, and thyroid cancer. Cancer Research 65: 1693–1699. [PubMed: 15753364]
    502.
    Lottin S. et al. (2005) The human H19 gene is frequently overexpressed in myometrium and stroma during pathological endometrial proliferative events. European Journal of Cancer 41: 168–177. [PubMed: 15618002]
    503.
    Barsyte-Lovejoy D. et al. (2006) The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Research 66: 5330–5337. [PubMed: 16707459]
    504.
    Matouk I.J. et al. (2007) The H19 non-coding RNA is essential for human tumor growth. PLOS ONE 2: e845. [PMC free article: PMC1959184] [PubMed: 17786216]
    505.
    Perez D.S. et al. (2008) Long, abundantly expressed non-coding transcripts are altered in cancer. Human Molecular Genetics 17: 642–655. [PubMed: 18006640]
    506.
    Yoshimizu T. et al. (2008) The H19 locus acts in vivo as a tumor suppressor. Proceedings of the National Academy of Sciences USA 105: 12417–12422. [PMC free article: PMC2527926] [PubMed: 18719115]
    507.
    Luo M. et al. (2013) Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Letters 333: 213–221. [PubMed: 23354591]
    508.
    Tseng Y.-Y. et al. (2014) PVT1 dependence in cancer with MYC copy-number increase. Nature 512: 82–86. [PMC free article: PMC4767149] [PubMed: 25043044]
    509.
    Prensner J.R. et al. (2014) PCAT-1: A long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer. Cancer Research 74: 1651–1660. [PMC free article: PMC4009928] [PubMed: 24473064]
    510.
    Iyer M.K. et al. (2015) The landscape of long noncoding RNAs in the human transcriptome. Nature Genetics 47: 199–208. [PMC free article: PMC4417758] [PubMed: 25599403]
    511.
    Adriaens C. et al. (2016) p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity. Nature Medicine 22: 861–868. [PubMed: 27376578]
    512.
    Liu Z. et al. (2018) Long non-coding RNA MIAT promotes growth and metastasis of colorectal cancer cells through regulation of miR-132/Derlin-1 pathway. Cancer Cell International 18: 59. [PMC free article: PMC5902964] [PubMed: 29686537]
    513.
    Alipoor F.J., Asadi M.H. and Torkzadeh-Mahani M. (2018) MIAT lncRNA is overexpressed in breast cancer and its inhibition triggers senescence and G1 arrest in MCF7 cell line. Journal of Cellular Biochemistry 119: 6470–6481. [PubMed: 29345338]
    514.
    Shin V.Y. et al. (2019) Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness. Cell Death & Disease 10: 270. [PMC free article: PMC6426882] [PubMed: 30894512]
    515.
    Dong P. et al. (2019) Long noncoding RNA NEAT1 drives aggressive endometrial cancer progression via miR-361-regulated networks involving STAT3 and tumor microenvironment-related genes. Journal of Experimental & Clinical Cancer Research 38: 295. [PMC free article: PMC6615218] [PubMed: 31287002]
    516.
    Chiu H.-S. et al. (2018) Pan-cancer analysis of lncRNA regulation supports their targeting of cancer genes in each tumor context. Cell Reports 23: 297–312. [PMC free article: PMC5906131] [PubMed: 29617668]
    517.
    Thapar R. et al. (2020) Mechanism of efficient double-strand break repair by a long non-coding RNA. Nucleic Acids Research 48: 10953–10972. [PMC free article: PMC7641761] [PubMed: 33045735]
    518.
    Tolomeo D., Agostini A., Visci G., Traversa D. and Tiziana Storlazzi C. (2021) PVT1: A long non-coding RNA recurrently involved in neoplasia-associated fusion transcripts. Gene 779: 145497. [PubMed: 33600954]
    519.
    Zhang J. et al. (2019) ALKBH5 promotes invasion and metastasis of gastric cancer by decreasing methylation of the lncRNA NEAT1. Journal of Physiology and Biochemistry 75: 379–389. [PMC free article: PMC6728298] [PubMed: 31290116]
    520.
    Saitou M., Sugimoto J., Hatakeyama T., Russo G. and Isobe M. (2000) Identification of the TCL6 genes within the breakpoint cluster region on chromosome 14q32 in T-cell leukemia. Oncogene 19: 2796–2802. [PubMed: 10851082]
    521.
    Tanaka R. et al. (2000) Intronic U50 small-nucleolar-RNA (snoRNA) host gene of no protein-coding potential is mapped at the chromosome breakpoint t(3;6)(q27;q15) of human B-cell lymphoma. Genes to Cells 5: 277–287. [PubMed: 10792466]
    522.
    Karreth F.A. et al. (2015) The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell 161: 319–332. [PMC free article: PMC6922011] [PubMed: 25843629]
    523.
    Fatima R., Choudhury S.R., Divya T. R., Bhaduri U. and Rao M.R.S. (2019) A novel enhancer RNA, Hmrhl, positively regulates its host gene, phkb, in chronic myelogenous leukemia. Noncoding RNA Research 4: 96–108. [PMC free article: PMC6926186] [PubMed: 31891018]
    524.
    Rahman S. and Mansour M.R. (2019) The role of noncoding mutations in blood cancers. Disease Models & Mechanisms 12: dmm041988. [PMC free article: PMC6899015] [PubMed: 31771951]
    525.
    Napoli S. et al. (2021) Characterization of GECPAR, a noncoding RNA that regulates the transcriptional program of diffuse large B cell lymphoma. Haematologica. epub ahead of print: https:​//haematologica​.org/article/view/haematol.2020.267096. [PMC free article: PMC9052922] [PubMed: 34162177]
    526.
    Leucci E. et al. (2016) Melanoma addiction to the long non-coding RNA SAMMSON. Nature 531: 518–522. [PubMed: 27008969]
    527.
    Hanniford D. et al. (2020) Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis. Cancer Cell 37: 55–70. [PMC free article: PMC7184928] [PubMed: 31935372]
    528.
    Chen S., Zhou L. and Wang Y. (2020) ALKBH5-mediated m6A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma. Cancer Cell International 20: 34. [PMC free article: PMC6993345] [PubMed: 32021563]
    529.
    Du T. et al. (2016) Decreased expression of long non-coding RNA WT1-AS promotes cell proliferation and invasion in gastric cancer. Biochimica et Biophysica Acta 1862: 12–19. [PubMed: 26449525]
    530.
    Zhang S., Guan Y., Liu X., Ju M. and Zhang Q. (2019) Long non-coding RNA DLEU1 exerts an oncogenic function in non-small cell lung cancer. Biomedicine & Pharmacotherapy 109: 985–990. [PubMed: 30551552]
    531.
    Zhang Y. et al. (2016) Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer. Nature Structural & Molecular Biology 23: 522–530. [PMC free article: PMC4927085] [PubMed: 27111890]
    532.
    Marjaneh M.M. et al. (2020) Non-coding RNAs underlie genetic predisposition to breast cancer. Genome Biology 21: 7. [PMC free article: PMC6947989] [PubMed: 31910864]
    533.
    Salameh A. et al. (2015) PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3. Proceedings of the National Academy of Sciences USA 112: 8403–8408. [PMC free article: PMC4500257] [PubMed: 26080435]
    534.
    Guo H. et al. (2016) Modulation of long noncoding RNAs by risk SNPs underlying genetic predispositions to prostate cancer. Nature Genetics 48: 1142–1150. [PubMed: 27526323]
    535.
    Hua J.T. et al. (2018) Risk SNP-mediated promoter-enhancer switching drives prostate cancer through lncRNA PCAT19. Cell 174: 564–575. [PubMed: 30033362]
    536.
    Xiong T. et al. (2020) LncRNA NRON promotes the proliferation, metastasis and EMT process in bladder cancer. Journal of Cancer 11: 1751–1760. [PMC free article: PMC7052857] [PubMed: 32194786]
    537.
    Li C. et al. (2017) A ROR1–HER3–lncRNA signalling axis modulates the Hippo–YAP pathway to regulate bone metastasis. Nature Cell Biology 19: 106–119. [PMC free article: PMC5336186] [PubMed: 28114269]
    538.
    Schmitt A.M. and Chang H.Y. (2016) Long noncoding RNAs in cancer pathways. Cancer Cell 29: 452–463. [PMC free article: PMC4831138] [PubMed: 27070700]
    539.
    Slack F.J. and Chinnaiyan A.M. (2019) The role of non-coding RNAs in oncology. Cell 179: 1033–1055. [PMC free article: PMC7347159] [PubMed: 31730848]
    540.
    Andergassen D. and Rinn J.L. (2021) From genotype to phenotype: Genetics of mammalian long non-coding RNAs in vivo. Nature Reviews Genetics 23: 229–243. [PubMed: 34837040]
    541.
    Ashburner M. et al. (1999) An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: The Adh region. Genetics 153: 179–219. [PMC free article: PMC1460734] [PubMed: 10471707]
    542.
    The C. elegans Sequencing Consortium (1998) Genome sequence of the nematode C. elegans: A platform for investigating biology. Science 282: 2012–2018. [PubMed: 9851916]
    543.
    Lek M. et al. (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536: 285–291. [PMC free article: PMC5018207] [PubMed: 27535533]
    544.
    Hayden E.C. (2016) A radical revision of human genetics: Why many ‘deadly’ gene mutations are turning out to be harmless. Nature 538: 154–157. [PubMed: 27734888]
    545.
    Lewejohann L. et al. (2004) Role of a neuronal small non-messenger RNA: Behavioural alterations in BC1 RNA-deleted mice. Behavioural Brain Research 154: 273–289. [PubMed: 15302134]
    546.
    Briz V. et al. (2017) The non-coding RNA BC1 regulates experience-dependent structural plasticity and learning. Nature Communications 8: 293. [PMC free article: PMC5561022] [PubMed: 28819097]
    547.
    Nakagawa S., Naganuma T., Shioi G. and Hirose T. (2011) Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice. Journal of Cell Biology 193: 31–39. [PMC free article: PMC3082198] [PubMed: 21444682]
    548.
    Nakagawa S. et al. (2012) Malat1 is not an essential component of nuclear speckles in mice. RNA 18: 1487–1499. [PMC free article: PMC3404370] [PubMed: 22718948]
    549.
    Nakagawa S. et al. (2014) The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice. Development 141: 4618–4627. [PMC free article: PMC4302932] [PubMed: 25359727]
    550.
    Kukharsky M.S. et al. (2020) Long non-coding RNA Neat1 regulates adaptive behavioural response to stress in mice. Translational Psychiatry 10: 171. [PMC free article: PMC7256041] [PubMed: 32467583]
    551.
    Gutschner T., Hämmerle M. and Diederichs S. (2013) MALAT1 — a paradigm for long noncoding RNA function in cancer. Journal of Molecular Medicine 91: 791–801. [PubMed: 23529762]
    552.
    Zhang X., Hamblin M.H. and Yin K.-J. (2017) The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biology 14: 1705–1714. [PMC free article: PMC5731810] [PubMed: 28837398]
    553.
    Ji Q. et al. (2019) MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 in colorectal cancer metastasis. Cell Death & Disease 10: 378. [PMC free article: PMC6522477] [PubMed: 31097689]
    554.
    Mehta S.L., Kim T. and Vemuganti R. (2015) Long noncoding RNA FosDT promotes ischemic brain injury by interacting with REST-associated chromatin-modifying proteins. Journal of Neuroscience 35: 16443–16449. [PMC free article: PMC4679824] [PubMed: 26674869]
    555.
    Mehta S.L. et al. (2021) Long noncoding RNA Fos Downstream Transcript is developmentally dispensable but vital for shaping the poststroke functional outcome. Stroke 52: 2381–2392. [PMC free article: PMC8238840] [PubMed: 33940958]
    556.
    Ramos A.D. et al. (2015) The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells. Cell Stem Cell 16: 439–447. [PMC free article: PMC4388801] [PubMed: 25800779]
    557.
    Andersen R.E. et al. (2019) The long noncoding RNA Pnky is a trans-acting regulator of cortical development in vivo. Developmental Cell 49: 632–642. [PMC free article: PMC6556063] [PubMed: 31112699]
    558.
    Sauvageau M. et al. (2013) Multiple knockout mouse models reveal lincRNAs are required for life and brain development. eLife 2: e01749. [PMC free article: PMC3874104] [PubMed: 24381249]
    559.
    Lai K.-M.V. et al. (2015) Diverse phenotypes and specific transcription patterns in twenty mouse lines with ablated lincRNAs. PLOS ONE 10: e0125522. [PMC free article: PMC4409293] [PubMed: 25909911]
    560.
    Ramilowski J.A. et al. (2020) Functional annotation of human long noncoding RNAs via molecular phenotyping. Genome Research 30: 1060–1072. [PMC free article: PMC7397864] [PubMed: 32718982]
    561.
    Cao H. et al. (2021) Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans. BMC Biology 19: 108. [PMC free article: PMC8139166] [PubMed: 34016118]
    562.
    Han X. et al. (2018) Mouse knockout models reveal largely dispensable but context-dependent functions of lncRNAs during development. Journal of Molecular Cell Biology 10: 175–178. [PubMed: 29420831]
    563.
    Willingham A.T. et al. (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309: 1570–1573. [PubMed: 16141075]
    564.
    Joung J. et al. (2017) Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood. Nature 548: 343–346. [PMC free article: PMC5706657] [PubMed: 28792927]
    565.
    Liu S. et al. (2020) Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation. Genome Medicine 12: 89. [PMC free article: PMC7580003] [PubMed: 33092630]
    566.
    Liu S.J. et al. (2020) CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma. Genome Biology 21: 83. [PMC free article: PMC7110660] [PubMed: 32234056]
    567.
    Zhao W. et al. (2016) The long noncoding RNA Sprightly regulates cell proliferation in primary human melanocytes. Journal of Investigative Dermatology 136: 819–828. [PMC free article: PMC4857189] [PubMed: 26829028]
    568.
    Wen K. et al. (2016) Critical roles of long noncoding RNAs in Drosophila spermatogenesis. Genome Research 26: 1233–1244. [PMC free article: PMC5052038] [PubMed: 27516619]
    569.
    Esposito R. et al. (2021) Multi-hallmark long noncoding RNA maps reveal non-small cell lung cancer vulnerabilities. bioRxiv: 2021.10.19.464956. [PMC free article: PMC9903773] [PubMed: 36778670]
    570.
    Liu Y. et al. (2018) Genome-wide screening for functional long noncoding RNAs in human cells by Cas9 targeting of splice sites. Nature Biotechnology 36: 1203–1210. [PubMed: 30395134]
    571.
    Liu S.J. et al. (2017) CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells. Science 355: eaah7111. [PMC free article: PMC5394926] [PubMed: 27980086]
    572.
    Rodriguez-Lopez M. et al. (2022) Functional profiling of long intergenic non-coding RNAs in fission yeast. eLife 11: e76000. [PMC free article: PMC8730722] [PubMed: 34984977]
    573.
    Wilkinson M.F. (2019) Genetic paradox explained by nonsense. Nature 568: 179–180. [PubMed: 30962551]
    574.
    Hong J.-W., Hendrix D.A. and Levine M.S. (2008) Shadow enhancers as a source of evolutionary novelty. Science 321: 1314. [PMC free article: PMC4257485] [PubMed: 18772429]
    575.
    Cannavò E. et al. (2016) Shadow enhancers are pervasive features of developmental regulatory networks. Current Biology 26: 38–51. [PMC free article: PMC4712172] [PubMed: 26687625]
    576.
    Osterwalder M. et al. (2018) Enhancer redundancy provides phenotypic robustness in mammalian development. Nature 554: 239–243. [PMC free article: PMC5808607] [PubMed: 29420474]
    577.
    Waymack R., Fletcher A., Enciso G. and Wunderlich Z. (2020) Shadow enhancers can suppress input transcription factor noise through distinct regulatory logic. eLife 9: e59351. [PMC free article: PMC7556877] [PubMed: 32804082]
    578.
    Kvon E.Z., Waymack R., Gad M. and Wunderlich Z. (2021) Enhancer redundancy in development and disease. Nature Reviews Genetics 22: 324–336. [PMC free article: PMC8068586] [PubMed: 33442000]
    579.
    Hirotsune S. et al. (2003) An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423: 91–96. [PubMed: 12721631]
    580.
    Zhang J. et al. (2006) NANOGP8 is a retrogene expressed in cancers. FEBS Journal 273: 1723–1730. [PubMed: 16623708]
    581.
    Tam O.H. et al. (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453: 534–538. [PMC free article: PMC2981145] [PubMed: 18404147]
    582.
    Poliseno L. et al. (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465: 1033–1038. [PMC free article: PMC3206313] [PubMed: 20577206]
    583.
    Johnsson P. et al. (2013) A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nature Structural & Molecular Biology 20: 440–446. [PMC free article: PMC3618526] [PubMed: 23435381]
    584.
    Chiang J.J. et al. (2018) Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity. Nature Immunology 19: 53–62. [PMC free article: PMC5815369] [PubMed: 29180807]
    585.
    Capel B. et al. (1993) Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell 73: 1019–1030. [PubMed: 7684656]
    586.
    Gruhl F., Janich P., Kaessmann H. and Gatfield D. (2021) Circular RNA repertoires are associated with evolutionarily young transposable elements. eLife 10: e67991. [PMC free article: PMC8516420] [PubMed: 34542406]
    587.
    Salzman J., Gawad C., Wang P.L., Lacayo N. and Brown P.O. (2012) Circular RNAs Are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLOS ONE 7: e30733. [PMC free article: PMC3270023] [PubMed: 22319583]
    588.
    Jeck W.R. et al. (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19: 426. [PMC free article: PMC3543092] [PubMed: 23249747]
    589.
    Patop I.L., Wüst S. and Kadener S. (2019) Past, present, and future of circRNAs. EMBO Journal 38: e100836. [PMC free article: PMC6694216] [PubMed: 31343080]
    590.
    Li Z. et al. (2015) Exon-intron circular RNAs regulate transcription in the nucleus. Nature Structural & Molecular Biology 22: 256–264. [PubMed: 25664725]
    591.
    Zhang Y. et al. (2013) Circular intronic long noncoding RNAs. Molecular Cell 51: 792–806. [PubMed: 24035497]
    592.
    Piwecka M. et al. (2017) Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science 357: eaam8526. [PubMed: 28798046]
    593.
    Suenkel C., Cavalli D., Massalini S., Calegari F. and Rajewsky N. (2020) A highly conserved circular RNA is required to keep neural cells in a progenitor state in the mammalian brain. Cell Reports 30: 2170–2179. [PubMed: 32075758]
    594.
    Hafez A.K. et al. (2022) A bidirectional competitive interaction between circHomer1 and Homer1b within the orbitofrontal cortex regulates reversal learning. Cell Reports 38: 110282. [PMC free article: PMC8809079] [PubMed: 35045295]
    595.
    Weigelt C.M. et al. (2020) An insulin-sensitive circular RNA that regulates lifespan in Drosophila. Molecular Cell 79: 268–279. [PMC free article: PMC7318944] [PubMed: 32592682]
    596.
    Liu Y. et al. (2020) Back-spliced RNA from retrotransposon binds to centromere and regulates centromeric chromatin loops in maize. PLOS Biology 18: e3000582. [PMC free article: PMC7010299] [PubMed: 31995554]
    597.
    Statello L., Guo C.-J., Chen L.-L. and Huarte M. (2021) Gene regulation by long non-coding RNAs and its biological functions. Nature Reviews Molecular Cell Biology 22: 96–118. [PMC free article: PMC7754182] [PubMed: 33353982]
    598.
    Harrow J. et al. (2006) GENCODE: Producing a reference annotation for ENCODE. Genome Biology 7: S4. [PMC free article: PMC1810553] [PubMed: 16925838]
    599.
    Frankish A. et al. (2021) GENCODE 2021. Nucleic Acids Research 49: D916–23. [PMC free article: PMC7778937] [PubMed: 33270111]
    600.
    The RNAcentral Consortium (2021) RNAcentral 2021: Secondary structure integration, improved sequence search and new member databases. Nucleic Acids Research 49: D212–20. [PMC free article: PMC7779037] [PubMed: 33106848]
    601.
    Uszczynska-Ratajczak B., Lagarde J., Frankish A., Guigó R. and Johnson R. (2018) Towards a complete map of the human long non-coding RNA transcriptome. Nature Reviews Genetics 19: 535–548. [PMC free article: PMC6451964] [PubMed: 29795125]
    602.
    Zimmer-Bensch G. (2019) Emerging roles of long non-coding RNAs as drivers of brain evolution. Cells 8: 1399. [PMC free article: PMC6912723] [PubMed: 31698782]
    603.
    Glinsky G. et al. (2018) Single cell expression analysis of primate-specific retroviruses-derived HPAT lincRNAs in viable human blastocysts identifies embryonic cells co-expressing genetic markers of multiple lineages. Heliyon 4: e00667. [PMC free article: PMC6039856] [PubMed: 30003161]
    604.
    Yang D. et al. (2018) N6-methyladenosine modification of lincRNA 1281 is critically required for mESC differentiation potential. Nucleic Acids Research 46: 3906–3920. [PMC free article: PMC5934679] [PubMed: 29529255]
    605.
    Jandura A. and Krause H.M. (2017) The new RNA world: Growing evidence for long noncoding RNA functionality. Trends in Genetics 33: 665–676. [PubMed: 28870653]
    606.
    Rinn J.L. and Chang H.Y. (2020) Long noncoding RNAs: Molecular modalities to organismal functions. Annual Review of Biochemistry 89: 283–308. [PubMed: 32569523]
    607.
    Flynn R.A. and Chang H.Y. (2014) Long noncoding RNAs in cell-fate programming and reprogramming. Cell Stem Cell 14: 752–761. [PMC free article: PMC4120821] [PubMed: 24905165]
    608.
    Fatica A. and Bozzoni I. (2014) Long non-coding RNAs: New players in cell differentiation and development. Nature Reviews Genetics 15: 7–21. [PubMed: 24296535]
    609.
    Xu M. et al. (2019) Long noncoding RNA SMRG regulates Drosophila macrochaetes by antagonizing scute through E(spl)mβ. RNA Biology 16: 42–53. [PMC free article: PMC6380328] [PubMed: 30526271]
    610.
    Zhang X., X.U. Yn, Chen B. and Kang L. (2020) Long noncoding RNA PAHAL modulates locust behavioural plasticity through the feedback regulation of dopamine biosynthesis. PLOS Genetics 16: e1008771. [PMC free article: PMC7241820] [PubMed: 32348314]
    611.
    Tang Y. et al. (2021) The long noncoding RNA FRILAIR regulates strawberry fruit ripening by functioning as a noncanonical target mimic. PLOS Genetics 17: e1009461. [PMC free article: PMC8011760] [PubMed: 33739974]
    612.
    Nowacki M., Shetty K. and Landweber L.F. (2011) RNA-mediated epigenetic programming of genome rearrangements. Annual Review of Genomics and Human Genetics 12: 367–389. [PMC free article: PMC3518427] [PubMed: 21801022]
    613.
    Andric V. et al. (2021) A scaffold lncRNA shapes the mitosis to meiosis switch. Nature Communications 12: 770. [PMC free article: PMC7859202] [PubMed: 33536434]
    614.
    Ding D.Q. et al. (2012) Meiosis-specific noncoding RNA mediates robust pairing of homologous chromosomes in meiosis. Science 336: 732–736. [PubMed: 22582262]
    615.
    Ding D.-Q. et al. (2019) Chromosome-associated RNA–protein complexes promote pairing of homologous chromosomes during meiosis in Schizosaccharomyces pombe. Nature Communications 10: 5598. [PMC free article: PMC6898681] [PubMed: 31811152]
    616.
    Parra-Rivero O., Pardo-Medina J., Gutiérrez G., Limón M.C. and Avalos J. (2020) A novel lncRNA as a positive regulator of carotenoid biosynthesis in Fusarium. Scientific Reports 10: 678. [PMC free article: PMC6971296] [PubMed: 31959816]
    617.
    Loewer S. et al. (2010) Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nature Genetics 42: 1113–1117. [PMC free article: PMC3040650] [PubMed: 21057500]
    618.
    Guttman M. et al. (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477: 295–300. [PMC free article: PMC3175327] [PubMed: 21874018]
    619.
    Klattenhoff C.A. et al. (2013) Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 152: 570–583. [PMC free article: PMC3563769] [PubMed: 23352431]
    620.
    Wang Y. et al. (2013) Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Developmental Cell 25: 69–80. [PubMed: 23541921]
    621.
    Lin N. et al. (2014) An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment. Molecular Cell 53: 1005–1019. [PMC free article: PMC4010157] [PubMed: 24530304]
    622.
    Yin Y. et al. (2015) Opposing roles for the lncRNA Haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation. Cell Stem Cell 16: 504–516. [PubMed: 25891907]
    623.
    Durruthy-Durruthy J. et al. (2016) The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming. Nature Genetics 48: 44–52. [PMC free article: PMC4827613] [PubMed: 26595768]
    624.
    Percharde M. et al. (2018) A LINE1-nucleolin partnership regulates early development and ESC identity. Cell 174: 391–405. [PMC free article: PMC6046266] [PubMed: 29937225]
    625.
    Zhu P. et al. (2018) LncGata6 maintains stemness of intestinal stem cells and promotes intestinal tumorigenesis. Nature Cell Biology 20: 1134–1144. [PubMed: 30224759]
    626.
    Yan P. et al. (2020) LncRNA Platr22 promotes super-enhancer activity and stem cell pluripotency. Journal of Molecular Cell Biology 13: 295–313. [PMC free article: PMC8339366] [PubMed: 33049031]
    627.
    Pal D. et al. (2021) LncRNA Mrhl orchestrates differentiation programs in mouse embryonic stem cells through chromatin mediated regulation. Stem Cell Research 53: 102250. [PubMed: 33662735]
    628.
    Wang H., Yang Y., Liu J. and Qian L. (2021) Direct cell reprogramming: Approaches, mechanisms and progress. Nature Reviews Molecular Cell Biology 22: 410–424. [PMC free article: PMC8161510] [PubMed: 33619373]
    629.
    Cipriano A. et al. (2021) Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells. eLife 10: e54782. [PMC free article: PMC7837680] [PubMed: 33432928]
    630.
    Guo Q. et al. (2014) BRAF‑activated long non‑coding RNA contributes to colorectal cancer migration by inducing epithelial‑mesenchymal transition. Oncology Letters 8: 869–875. [PMC free article: PMC4081361] [PubMed: 25013510]
    631.
    Dill T.L., Carroll A., Pinheiro A., Gao J. and Naya F.J. (2021) The long noncoding RNA Meg3 regulates myoblast plasticity and muscle regeneration through epithelial-mesenchymal transition. Development 148: dev194027. [PubMed: 33298462]
    632.
    Luo S. et al. (2016) Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell 18: 637–652. [PubMed: 26996597]
    633.
    Daneshvar K. et al. (2016) DIGIT Is a conserved long noncoding RNA that regulates GSC expression to control definitive endoderm differentiation of embryonic stem cells. Cell Reports 17: 353–365. [PMC free article: PMC5120872] [PubMed: 27705785]
    634.
    Alexanian M. et al. (2017) A transcribed enhancer dictates mesendoderm specification in pluripotency. Nature Communications 8: 1806. [PMC free article: PMC5703900] [PubMed: 29180618]
    635.
    Yoneda R., Ueda N., Uranishi K., Hirasaki M. and Kurokawa R. (2020) Long noncoding RNA pncRNA-D reduces cyclin D1 gene expression and arrests cell cycle through RNA m6A modification. Journal of Biological Chemistry 295: 5626–5639. [PMC free article: PMC7186179] [PubMed: 32165496]
    636.
    Pruunsild P., Kazantseva A., Aid T., Palm K. and Timmusk T. (2007) Dissecting the human BDNF locus: Bidirectional transcription, complex splicing, and multiple promoters. Genomics 90: 397–406. [PMC free article: PMC2568880] [PubMed: 17629449]
    637.
    Modarresi F. et al. (2012) Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nature Biotechnology 30: 453–459. [PMC free article: PMC4144683] [PubMed: 22446693]
    638.
    Wilson K.D. et al. (2020) Endogenous retrovirus-derived lncRNA BANCR promotes cardiomyocyte migration in humans and non-human primates. Developmental Cell 54: 694–709. [PMC free article: PMC7529962] [PubMed: 32763147]
    639.
    Wang X. et al. (2021) Mutual dependency between lncRNA LETN and protein NPM1 in controlling the nucleolar structure and functions sustaining cell proliferation. Cell Research 31: 664–683. [PMC free article: PMC8169757] [PubMed: 33432115]
    640.
    Ducoli L. et al. (2021) LETR1 is a lymphatic endothelial-specific lncRNA governing cell proliferation and migration through KLF4 and SEMA3C. Nature Communications 12: 925. [PMC free article: PMC7876020] [PubMed: 33568674]
    641.
    Huang D. et al. (2018) NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death. Nature Immunology 19: 1112–1125. [PubMed: 30224822]
    642.
    Briggs J.A., Wolvetang E.J., Mattick J.S., Rinn J.L. and Barry G. (2015) Mechanisms of long non-coding RNAs in mammalian nervous system development, plasticity, disease, and evolution. Neuron 88: 861–877. [PubMed: 26637795]
    643.
    Onoguchi M., Hirabayashi Y., Koseki H. and Gotoh Y. (2012) A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development. Proceedings of the National Academy of Sciences USA 109: 16939–16944. [PMC free article: PMC3479495] [PubMed: 23027973]
    644.
    Cajigas I. et al. (2018) The Evf2 ultraconserved enhancer lncRNA functionally and spatially organizes megabase distant genes in the developing forebrain. Molecular Cell 71: 956–972. [PMC free article: PMC6428050] [PubMed: 30146317]
    645.
    Cajigas I. et al. (2021) Sox2-Evf2 lncRNA mechanisms of chromosome topological control in developing forebrain. Development 148: dev197202. [PMC free article: PMC7990859] [PubMed: 33593819]
    646.
    Rapicavoli N.A., Poth E.M. and Blackshaw S. (2010) The long noncoding RNA RNCR2 directs mouse retinal cell specification. BMC Developmental Biology 10: 49. [PMC free article: PMC2876091] [PubMed: 20459797]
    647.
    Krol J. et al. (2015) A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture. Nature Communications 6: 7305. [PMC free article: PMC4468907] [PubMed: 26041499]
    648.
    Bond A.M. et al. (2009) Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. Nature Neuroscience 12: 1020–1027. [PMC free article: PMC3203213] [PubMed: 19620975]
    649.
    Rea J. et al. (2020) HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade. Cell Death & Disease 11: 527. [PMC free article: PMC7359305] [PubMed: 32661334]
    650.
    Hollensen A.K. et al. (2020) circZNF827 nucleates a transcription inhibitory complex to balance neuronal differentiation. eLife 9: e58478. [PMC free article: PMC7657652] [PubMed: 33174841]
    651.
    Perry R.B.-T., Hezroni H., Goldrich M.J. and Ulitsky I. (2018) Regulation of neuroregeneration by long noncoding RNAs. Molecular Cell 72: 553–567. [PMC free article: PMC6542662] [PubMed: 30401432]
    652.
    Grelet S. et al. (2022) TGFβ-induced expression of long noncoding lincRNA Platr18 controls breast cancer axonogenesis. Life Science Alliance 5: e202101261. [PMC free article: PMC8645334] [PubMed: 34810279]
    653.
    Andreassi C. et al. (2021) Cytoplasmic cleavage of IMPA1 3′ UTR is necessary for maintaining axon integrity. Cell Reports 34: 108778. [PMC free article: PMC7918530] [PubMed: 33626357]
    654.
    Martinez-Moreno M. et al. (2017) Regulation of peripheral myelination through transcriptional buffering of Egr2 by an antisense long non-coding RNA. Cell Reports 20: 1950–1963. [PMC free article: PMC5800313] [PubMed: 28834756]
    655.
    Bernard D. et al. (2010) A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO Journal 29: 3082–3093. [PMC free article: PMC2944070] [PubMed: 20729808]
    656.
    You X. et al. (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nature Neuroscience 18: 603–610. [PMC free article: PMC4376664] [PubMed: 25714049]
    657.
    Raveendra B.L. et al. (2018) Long noncoding RNA GM12371 acts as a transcriptional regulator of synapse function. Proceedings of the National Academy of Sciences USA 115: E10197–205. [PMC free article: PMC6205475] [PubMed: 30297415]
    658.
    Ma M. et al. (2020) A novel pathway regulates social hierarchy via lncRNA AtLAS and postsynaptic synapsin IIb. Cell Research 30: 105–118. [PMC free article: PMC7015055] [PubMed: 31959917]
    659.
    Wang F. et al. (2021) The long noncoding RNA Synage regulates synapse stability and neuronal function in the cerebellum. Cell Death & Differentiation 28: 2634–2650. [PMC free article: PMC8408218] [PubMed: 33762741]
    660.
    Grinman E. et al. (2021) Activity-regulated synaptic targeting of lncRNA ADEPTR mediates structural plasticity by localizing Sptn1 and AnkB in dendrites. Science Advances 7: eabf0605. [PMC free article: PMC8051873] [PubMed: 33863727]
    661.
    Li D. et al. (2018) Activity dependent LoNA regulates translation by coordinating rRNA transcription and methylation. Nature Communications 9: 1726. [PMC free article: PMC5928123] [PubMed: 29712923]
    662.
    Li X. et al. (2021) On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3. bioRxiv: 2021.08.01.454607. [PMC free article: PMC9015815] [PubMed: 35320727]
    663.
    Issler O. et al. (2020) Sex-specific role for the long non-coding RNA LINC00473 in depression. Neuron 106: 912–926. [PMC free article: PMC7305959] [PubMed: 32304628]
    664.
    Shore A.N. et al. (2012) Pregnancy-induced noncoding RNA (PINC) associates with polycomb repressive complex 2 and regulates mammary epithelial differentiation. PLOS Genetics 8: e1002840. [PMC free article: PMC3406180] [PubMed: 22911650]
    665.
    Stafford D.A., Dichmann D.S., Chang J.K. and Harland R.M. (2017) Deletion of the sclerotome-enriched lncRNA PEAT augments ribosomal protein expression. Proceedings of the National Academy of Sciences USA 114: 101–106. [PMC free article: PMC5224379] [PubMed: 27986952]
    666.
    Grote P. et al. (2013) The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Developmental Cell 24: 206–214. [PMC free article: PMC4149175] [PubMed: 23369715]
    667.
    Anderson K.M. et al. (2016) Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development. Nature 539: 433–436. [PMC free article: PMC5261552] [PubMed: 27783597]
    668.
    Han X. et al. (2019) The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression of Hand2. Development 146: dev176198. [PubMed: 31273086]
    669.
    Ritter N. et al. (2019) The lncRNA locus Handsdown regulates cardiac gene programs and is essential for early mouse development. Developmental Cell 50: 644–657. [PubMed: 31422919]
    670.
    Szafranski P. et al. (2013) Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder. Genome Research 23: 23–33. [PMC free article: PMC3530681] [PubMed: 23034409]
    671.
    Delpretti S. et al. (2013) Multiple enhancers regulate Hoxd genes and the Hotdog lncRNA during cecum budding. Cell Reports 5: 137–150. [PubMed: 24075990]
    672.
    Cesana M. et al. (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147: 358–369. [PMC free article: PMC3234495] [PubMed: 22000014]
    673.
    Ounzain S. et al. (2015) CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. Journal of Molecular and Cellular Cardiology 89: 98–112. [PubMed: 26423156]
    674.
    Wang Z. et al. (2016) The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy. Nature Medicine 22: 1131–1139. [PMC free article: PMC5053883] [PubMed: 27618650]
    675.
    Liu J., Li Y., Lin B., Sheng Y. and Yang L. (2017) HBL1 Is a human long noncoding RNA that modulates cardiomyocyte development from pluripotent stem cells by counteracting MIR1. Developmental Cell 42: 333–348. [PMC free article: PMC5567988] [PubMed: 28829943]
    676.
    Micheletti R. et al. (2017) The long noncoding RNA Wisper controls cardiac fibrosis and remodeling. Science Translational Medicine 9: eaai9118. [PMC free article: PMC5643582] [PubMed: 28637928]
    677.
    Ballarino M. et al. (2018) Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice. EMBO Journal 37: e99697. [PMC free article: PMC6138438] [PubMed: 30177572]
    678.
    Alessio E. et al. (2019) Single cell analysis reveals the involvement of the long non-coding RNA Pvt1 in the modulation of muscle atrophy and mitochondrial network. Nucleic Acids Research 47: 1653–1670. [PMC free article: PMC6393313] [PubMed: 30649422]
    679.
    Kang X., Zhao Y., Van Arsdell G., Nelson S.F. and Touma M. (2020) Ppp1r1b-lncRNA inhibits PRC2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human. RNA 26: 481–491. [PMC free article: PMC7075267] [PubMed: 31953255]
    680.
    Schutt C. et al. (2020) Linc-MYH configures INO80 to regulate muscle stem cell numbers and skeletal muscle hypertrophy. EMBO Journal 39: e105098. [PMC free article: PMC7667881] [PubMed: 32960481]
    681.
    Dong K. et al. (2021) CARMN Is an evolutionarily conserved smooth muscle cell-specific lncRNA that maintains contractile phenotype by binding myocardin. Circulation 144: 1856–1875. [PMC free article: PMC8726016] [PubMed: 34694145]
    682.
    Anderson D.M. et al. (2021) A myocardin-adjacent lncRNA balances SRF-dependent gene transcription in the heart. Genes & Development 35: 835–840. [PMC free article: PMC8168554] [PubMed: 33985971]
    683.
    Sato M. et al. (2021) The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis. Nature Communications 12: 2529. [PMC free article: PMC8099897] [PubMed: 33953175]
    684.
    Vacante F. et al. (2021) CARMN loss regulates smooth muscle cells and accelerates atherosclerosis in mice. Circulation Research 128: 1258–1275. [PMC free article: PMC7610708] [PubMed: 33622045]
    685.
    Lu L. et al. (2013) Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis. EMBO journal 32: 2575–2588. [PMC free article: PMC3791367] [PubMed: 23942234]
    686.
    Legnini I., Morlando M., Mangiavacchi A., Fatica A. and Bozzoni I. (2014) A feedforward regulatory loop between HuR and the long noncoding RNA linc-MD1 controls early phases of myogenesis. Molecular Cell 53: 506–514. [PMC free article: PMC3919156] [PubMed: 24440503]
    687.
    Raz V., Riaz M., Tatum Z., Kielbasa S.M. and t Hoen P.A.C. (2018) The distinct transcriptomes of slow and fast adult muscles are delineated by noncoding RNAs. FASEB Journal 32: 1579–1590. [PubMed: 29141996]
    688.
    Dou M. et al. (2020) The long noncoding RNA MyHC IIA/X-AS contributes to skeletal muscle myogenesis and maintains the fast fiber phenotype. Journal of Biological Chemistry 295: 4937–4949. [PMC free article: PMC7152763] [PubMed: 32152230]
    689.
    Yu J.-A. et al. (2021) LncRNA-FKBP1C regulates muscle fiber type switching by affecting the stability of MYH1B. Cell Death Discovery 7: 73. [PMC free article: PMC8035166] [PubMed: 33837177]
    690.
    Cai B. et al. (2021) Long noncoding RNA SMUL suppresses SMURF2 production-mediated muscle atrophy via nonsense-mediated mRNA decay. Molecular Therapy - Nucleic Acids 23: 512–526. [PMC free article: PMC7807096] [PubMed: 33510940]
    691.
    Wang Y. et al. (2018) Long noncoding RNA lncHand2 promotes liver repopulation via c-Met signaling. Journal of Hepatology 69: 861–872. [PubMed: 29653123]
    692.
    Wang Y. et al. (2019) LncRNA HAND2-AS1 promotes liver cancer stem cell self-renewal via BMP signaling. EMBO Journal 38: e101110. [PMC free article: PMC6717889] [PubMed: 31334575]
    693.
    Hennessy E.J. et al. (2019) The long noncoding RNA CHROME regulates cholesterol homeostasis in primates. Nature Metabolism 1: 98–110. [PMC free article: PMC6691505] [PubMed: 31410392]
    694.
    Leisegang M.S. et al. (2017) Long noncoding RNA MANTIS facilitates endothelial angiogenic function. Circulation 136: 65–79. [PMC free article: PMC5491227] [PubMed: 28351900]
    695.
    Mushimiyimana I. et al. (2021) Genomic landscapes of noncoding RNAs regulating VEGFA and VEGFC expression in endothelial cells. Molecular and Cellular Biology 41: e00594-20. [PMC free article: PMC8224232] [PubMed: 33875575]
    696.
    Chignon A. et al. (2022) Genome-wide chromatin contacts of super-enhancer-associated lncRNA identify LINC01013 as a regulator of fibrosis in the aortic valve. PLOS Genetics 18: e1010010. [PMC free article: PMC8797204] [PubMed: 35041643]
    697.
    Lyu Q. et al. (2019) SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4. Proceedings of the National Academy of Sciences USA 116: 546–555. [PMC free article: PMC6329947] [PubMed: 30584103]
    698.
    Sehgal P. et al. (2021) LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy. EMBO Journal 2021: e107134. [PMC free article: PMC8327952] [PubMed: 34180064]
    699.
    Lewandowski J.P. et al. (2019) The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesis. Nature Communications 10: 5137. [PMC free article: PMC6853988] [PubMed: 31723143]
    700.
    Ranzani V. et al. (2015) The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4. Nature Immunology 16: 318–325. [PMC free article: PMC4333215] [PubMed: 25621826]
    701.
    Kretz M. et al. (2012) Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes & development 26: 338–343. [PMC free article: PMC3289881] [PubMed: 22302877]
    702.
    Kretz M. et al. (2013) Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493: 231–235. [PMC free article: PMC3674581] [PubMed: 23201690]
    703.
    Cai P. et al. (2019) A genome-wide long noncoding RNA CRISPRi screen identifies PRANCR as a novel regulator of epidermal homeostasis. Genome Research 30: 22–34. [PMC free article: PMC6961571] [PubMed: 31804951]
    704.
    Arriaga-Canon C. et al. (2014) A long non-coding RNA promotes full activation of adult gene expression in the chicken α-globin domain. Epigenetics 9: 173–181. [PMC free article: PMC3928180] [PubMed: 24196393]
    705.
    Werner M.S. et al. (2017) Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription. Nature Structural & Molecular Biology 24: 596–603. [PMC free article: PMC5682930] [PubMed: 28628087]
    706.
    Alvarez-Dominguez J.R., Knoll M., Gromatzky A.A. and Lodish H.F. (2017) The super-enhancer-derived alncRNA-EC7/Bloodlinc potentiates red blood cell development in trans. Cell Reports 19: 2503–2514. [PMC free article: PMC6013260] [PubMed: 28636939]
    707.
    Morrison T.A. et al. (2018) A long noncoding RNA from the HBS1L-MYB intergenic region on chr6q23 regulates human fetal hemoglobin expression. Blood Cells, Molecules, and Diseases 69: 1–9. [PMC free article: PMC5783741] [PubMed: 29227829]
    708.
    Jiang M. et al. (2018) Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response. Cell 173: 906–919. [PubMed: 29706547]
    709.
    Zhou B. et al. (2019) Endogenous retrovirus-derived long noncoding RNA enhances innate immune responses via derepressing RELA expression. mBio 10: e00937-19. [PMC free article: PMC6667616] [PubMed: 31363026]
    710.
    Liu W. et al. (2020) LncRNA Malat1 inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity. Proceedings of the National Academy of Sciences USA 117: 23695–23706. [PMC free article: PMC7519350] [PubMed: 32907941]
    711.
    Hewitson J.P. et al. (2020) Malat1 suppresses immunity to infection through promoting expression of Maf and IL-10 in Th cells. Journal of Immunology 204: 2949–2960. [PMC free article: PMC7231852] [PubMed: 32321759]
    712.
    Flores-Concha M. and Oñate Á.A. (2020) Long non-coding RNAs in the regulation of the immune response and trained immunity. Frontiers in Genetics 11: 718. [PMC free article: PMC7393263] [PubMed: 32793280]
    713.
    Kotzin J.J. et al. (2019) The long noncoding RNA Morrbid regulates CD8 T cells in response to viral infection. Proceedings of the National Academy of Sciences USA 116: 11916–11925. [PMC free article: PMC6575676] [PubMed: 31138702]
    714.
    Lai C. et al. (2021) Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a. Cell Death & Differentiation 28: 2900–2915. [PMC free article: PMC8481484] [PubMed: 33990776]
    715.
    Peltier D. et al. (2021) RNA-seq of human T cells after hematopoietic stem cell transplantation identifies Linc00402 as a regulator of T cell alloimmunity. Science Translational Medicine 13: eaaz0316. [PMC free article: PMC8589011] [PubMed: 33731431]
    716.
    Sui B. et al. (2020) A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation. Genome Biology 21: 228. [PMC free article: PMC7465408] [PubMed: 32873321]
    717.
    Vigneau S., Rohrlich P.S., Brahic M. and Bureau J.F. (2003) Tmevpg1, a candidate gene for the control of Theiler’s virus persistence, could be implicated in the regulation of gamma interferon. Journal of Virology 77: 5632–5638. [PMC free article: PMC154023] [PubMed: 12719555]
    718.
    Collier S.P., Collins P.L., Williams C.L., Boothby M.R. and Aune T.M. (2012) Cutting edge: Influence of Tmevpg1, a long intergenic noncoding RNA, on the expression of Ifng by Th1 cells. Journal of Immunology 189: 2084–2088. [PMC free article: PMC3424368] [PubMed: 22851706]
    719.
    Gomez J.A. et al. (2013) The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-gamma locus. Cell 152: 743–754. [PMC free article: PMC3577098] [PubMed: 23415224]
    720.
    Stein N. et al. (2019) IFNG-AS1 enhances interferon gamma production in human natural killer cells. iScience 11: 466–473. [PMC free article: PMC6354656] [PubMed: 30661002]
    721.
    Vollmers A.C. et al. (2021) A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock. Proceedings of the National Academy of Sciences USA 118: e2016648118. [PMC free article: PMC7896317] [PubMed: 33568531]
    722.
    Rothschild G. et al. (2020) Noncoding RNA transcription alters chromosomal topology to promote isotype-specific class switch recombination. Science Immunology 5: eaay5864. [PMC free article: PMC7608691] [PubMed: 32034089]
    723.
    Nair L. et al. (2021) Mechanism of noncoding RNA-associated N6-methyladenosine recognition by an RNA processing complex during IgH DNA recombination. Molecular Cell 81: 3949–3964. [PMC free article: PMC8571800] [PubMed: 34450044]
    724.
    Zhao X. et al. (2013) A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons. Nature Neuroscience 16: 1024–1031. [PMC free article: PMC3742386] [PubMed: 23792947]
    725.
    Atianand M.K. et al. (2016) A long noncoding RNA lincRNA-EPS acts as a transcriptional brake to restrain inflammation. Cell 165: 1672–1685. [PMC free article: PMC5289747] [PubMed: 27315481]
    726.
    Hu G. et al. (2016) LincRNA-Cox2 promotes late inflammatory gene transcription in macrophages through modulating SWI/SNF-mediated chromatin remodeling. Journal of Immunology 196: 2799–2808. [PMC free article: PMC4779692] [PubMed: 26880762]
    727.
    Liu X. et al. (2019) A long noncoding RNA, Antisense IL-7, promotes inflammatory gene transcription through facilitating histone acetylation and switch/sucrose nonfermentable chromatin remodeling. Journal of Immunology 203: 1548–1559. [PubMed: 31383742]
    728.
    Miyata K. et al. (2021) Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer. Proceedings of the National Academy of Sciences USA 118: e2025647118. [PMC free article: PMC8536346] [PubMed: 34426493]
    729.
    Du Q. et al. (2019) MIR205HG Is a long noncoding RNA that regulates growth hormone and prolactin production in the anterior pituitary. Developmental Cell 49: 618–631. [PMC free article: PMC9131289] [PubMed: 30982661]
    730.
    Liang L. et al. (2021) The long noncoding RNA HOTAIRM1 controlled by AML1 enhances glucocorticoid resistance by activating RHOA/ROCK1 pathway through suppressing ARHGAP18. Cell Death & Disease 12: 702. [PMC free article: PMC8280127] [PubMed: 34262023]
    731.
    Heinen T.J.A.J., Staubach F., Häming D. and Tautz D. (2009) Emergence of a new gene from an intergenic region. Current Biology 19: 1527–1531. [PubMed: 19733073]
    732.
    Nakajima R., Sato T., Ogawa T., Okano H. and Noce T. (2017) A noncoding RNA containing a SINE-B1 motif associates with meiotic metaphase chromatin and has an indispensable function during spermatogenesis. PLOS ONE 12: e0179585. [PMC free article: PMC5489172] [PubMed: 28658256]
    733.
    Bouska M.J. and Bai H. (2021) Long noncoding RNA regulation of spermatogenesis via the spectrin cytoskeleton in Drosophila. G3 (Genes, Genomes, Genetics) 11: jkab080. [PMC free article: PMC8104941] [PubMed: 33720346]
    734.
    Schmitt A.M. et al. (2016) An inducible long noncoding RNA amplifies DNA damage signaling. Nature Genetics 48: 1370–1376. [PMC free article: PMC5083181] [PubMed: 27668660]
    735.
    Michelini F. et al. (2017) Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Nature Cell Biology 19: 1400–1411. [PMC free article: PMC5714282] [PubMed: 29180822]
    736.
    Tran K.-V. et al. (2020) Human thermogenic adipocyte regulation by the long noncoding RNA LINC00473. Nature Metabolism 2: 397–412. [PMC free article: PMC7241442] [PubMed: 32440655]
    737.
    Scheele C. et al. (2007) The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function. BMC Genomics 8: 74. [PMC free article: PMC1831481] [PubMed: 17362513]
    738.
    Lanz R.B. et al. (1999) A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97: 17–27. [PubMed: 10199399]
    739.
    Lanz R.B., Razani B., Goldberg A.D. and O‘Malley B.W. (2002) Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proceedings of the National Academy of Sciences USA 99: 16081–16086. [PMC free article: PMC138568] [PubMed: 12444263]
    740.
    Kino T., Hurt D.E., Ichijo T., Nader N. and Chrousos G.P. (2010) Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Science Signaling 3: ra8. [PMC free article: PMC2819218] [PubMed: 20124551]
    741.
    Campalans A., Kondorosi A. and Crespi M. (2004) Enod40, a short open reading frame-containing mRNA, induces cytoplasmic localization of a nuclear RNA binding protein in Medicago truncatula. Plant Cell 16: 1047–1059. [PMC free article: PMC412876] [PubMed: 15037734]
    742.
    Khvorova A., Kwak Y.-G., Tamkun M., Majerfeld I. and Yarus M. (1999) RNAs that bind and change the permeability of phospholipid membranes. Proceedings of the National Academy of Sciences USA 96: 10649–10654. [PMC free article: PMC17937] [PubMed: 10485880]
    743.
    McClintock M.A. et al. (2018) RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs. eLife 7: e36312. [PMC free article: PMC6056234] [PubMed: 29944118]
    744.
    Lin A. et al. (2017) The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors. Nature Cell Biology 19: 238–251. [PMC free article: PMC5332298] [PubMed: 28218907]
    745.
    Sang L. et al. (2018) LncRNA CamK-A regulates Ca2+-signaling-mediated tumor microenvironment remodeling. Molecular Cell 72: 71–83. [PubMed: 30220561]
    746.
    Ma Y., Zhang J., Wen L. and Lin A. (2018) Membrane-lipid associated lncRNA: A new regulator in cancer signaling. Cancer Letters 419: 27–29. [PubMed: 29330108]
    747.
    Zheng X. et al. (2017) LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism. EMBO Journal 36: 3325–3335. [PMC free article: PMC5686550] [PubMed: 28963395]
    748.
    Zucchelli S. et al. (2015) SINEUPs: A new class of natural and synthetic antisense long non-coding RNAs that activate translation. RNA Biology 12: 771–779. [PMC free article: PMC4615742] [PubMed: 26259533]
    749.
    Wang H. et al. (2005) Dendritic BC1 RNA in translational control mechanisms. Journal of Cell Biology 171: 811–821. [PMC free article: PMC1828541] [PubMed: 16330711]
    750.
    Deforges J. et al. (2019) Control of cognate sense mRNA translation by cis-natural antisense RNAs. Plant Physiology 180: 305–322. [PMC free article: PMC6501089] [PubMed: 30760640]
    751.
    Munroe S.H. and Lazar M.A. (1991) Inhibition of c-erbA mRNA splicing by a naturally occurring antisense RNA. Journal of Biological Chemistry 266: 22083–22086. [PubMed: 1657988]
    752.
    Yan M.D. et al. (2005) Identification and characterization of a novel gene Saf transcribed from the opposite strand of Fas. Human Molecular Genetics 14: 1465–1474. [PubMed: 15829500]
    753.
    Kishore S. and Stamm S. (2006) The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 311: 230–232. [PubMed: 16357227]
    754.
    Beltran M. et al. (2008) A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes & Development 22: 756–769. [PMC free article: PMC2275429] [PubMed: 18347095]
    755.
    Tripathi V. et al. (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Molecular Cell 39: 925–938. [PMC free article: PMC4158944] [PubMed: 20797886]
    756.
    Morrissy A.S., Griffith M. and Marra M.A. (2011) Extensive relationship between antisense transcription and alternative splicing in the human genome. Genome Research 21: 1203–1212. [PMC free article: PMC3149488] [PubMed: 21719572]
    757.
    Gonzalez I. et al. (2015) A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature. Nature Structural & Molecular Biology 22: 370–376. [PMC free article: PMC6322542] [PubMed: 25849144]
    758.
    Yap K. et al. (2018) A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival. Molecular Cell 72: 525–540. [PMC free article: PMC6224606] [PubMed: 30318443]
    759.
    Romero-Barrios N., Legascue M.F., Benhamed M., Ariel F. and Crespi M. (2018) Splicing regulation by long noncoding RNAs. Nucleic Acids Research 46: 2169–2184. [PMC free article: PMC5861421] [PubMed: 29425321]
    760.
    Pisignano G. and Ladomery M. (2021) Epigenetic regulation of alternative splicing: How lncRNAs tailor the message. Non-Coding RNA 7: 21. [PMC free article: PMC8005942] [PubMed: 33799493]
    761.
    Otten A.B.C. et al. (2021) The noncoding RNA PRANCR regulates splicing of Fibronectin-1 to control keratinocyte proliferation and migration. bioRxiv: 2021.06.22.449364.
    762.
    Simone R. et al. (2021) MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration. Nature 594: 117–123. [PMC free article: PMC7610982] [PubMed: 34012113]
    763.
    Peters N.T., Rohrbach J.A., Zalewski B.A., Byrkett C.M. and Vaughn J.C. (2003) RNA editing and regulation of Drosophila 4f-rnp expression by sas-10 antisense readthrough mRNA transcripts. RNA 9: 698–710. [PMC free article: PMC1370437] [PubMed: 12756328]
    764.
    Prasanth K.V. et al. (2005) Regulating gene expression through RNA nuclear retention. Cell 123: 249–263. [PubMed: 16239143]
    765.
    Werner A. (2005) Natural antisense transcripts. RNA Biology 2: 53–62. [PubMed: 17132938]
    766.
    Li K. et al. (2010) A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo. Blood 115: 133–139. [PMC free article: PMC2803688] [PubMed: 19880500]
    767.
    Gong C. and Maquat L.E. (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470: 284–288. [PMC free article: PMC3073508] [PubMed: 21307942]
    768.
    Goodrich J.A. and Kugel J.F. (2006) Non-coding-RNA regulators of RNA polymerase II transcription. Nature Reviews Molecular Cell Biology 7: 612–616. [PubMed: 16723972]
    769.
    Studniarek C., Egloff S. and Murphy S. (2021) Noncoding RNAs set the stage for RNA Polymerase II transcription. Trends in Genetics 37: 279–291. [PubMed: 33046273]
    770.
    Yang Z., Zhu Q., Luo K. and Zhou Q. (2001) The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414: 317–322. [PubMed: 11713532]
    771.
    Nguyen V.T., Kiss T., Michels A.A. and Bensaude O. (2001) 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414: 322–325. [PubMed: 11713533]
    772.
    Kohoutek J. (2009) P-TEFb- the final frontier. Cell Division 4: 19. [PMC free article: PMC2748068] [PubMed: 19723344]
    773.
    Lenasi T. and Barboric M. (2010) P-TEFb stimulates transcription elongation and pre-mRNA splicing through multilateral mechanisms. RNA Biology 7: 145–150. [PubMed: 20305375]
    774.
    Peterlin B.M., Brogie J.E. and Price D.H. (2012) 7SK snRNA: A noncoding RNA that plays a major role in regulating eukaryotic transcription. Wiley Interdisciplinary Reviews RNA 3: 92–103. [PMC free article: PMC3223291] [PubMed: 21853533]
    775.
    Castelo-Branco G. et al. (2013) The non-coding snRNA 7SK controls transcriptional termination, poising, and bidirectionality in embryonic stem cells. Genome Biology 14: R98. [PMC free article: PMC4053805] [PubMed: 24044525]
    776.
    Quaresma A.J.C., Bugai A. and Barboric M. (2016) Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb. Nucleic Acids Research 44: 7527–7539. [PMC free article: PMC5027500] [PubMed: 27369380]
    777.
    Flynn R.A. et al. (2016) 7SK-BAF axis controls pervasive transcription at enhancers. Nature Structural & Molecular Biology 23: 231–238. [PMC free article: PMC4982704] [PubMed: 26878240]
    778.
    Studniarek C. et al. (2021) The 7SK/P-TEFb snRNP controls ultraviolet radiation-induced transcriptional reprogramming. Cell Reports 35: 108965. [PubMed: 33852864]
    779.
    Egloff S., Studniarek C. and Kiss T. (2018) 7SK small nuclear RNA, a multifunctional transcriptional regulatory RNA with gene-specific features. Transcription 9: 95–101. [PMC free article: PMC5834218] [PubMed: 28820318]
    780.
    Briese M. and Sendtner M. (2021) Keeping the balance: The noncoding RNA 7SK as a master regulator for neuron development and function. Bioessays 43: e2100092. [PubMed: 34050960]
    781.
    Wang X. et al. (2008) Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454: 126–130. [PMC free article: PMC2823488] [PubMed: 18509338]
    782.
    Martianov I., Ramadass A., Serra Barros A., Chow N. and Akoulitchev A. (2007) Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature 445: 666–670. [PubMed: 17237763]
    783.
    Li Y., Syed J. and Sugiyama H. (2016) RNA-DNA triplex formation by long noncoding RNAs. Cell Chemical Biology 23: 1325–1333. [PubMed: 27773629]
    784.
    Imamura T. et al. (2004) Non-coding RNA directed DNA demethylation of Sphk1 CpG island. Biochemical and Biophysical Research Communications 322: 593–600. [PubMed: 15325271]
    785.
    Postepska-Igielska A. et al. (2015) LncRNA Khps1 regulates expression of the proto-oncogene SPHK1 via triplex-mediated changes in chromatin structure. Molecular Cell 60: 626–636. [PubMed: 26590717]
    786.
    Fan S. et al. (2020) lncRNA CISAL Inhibits BRCA1 transcription by forming a tertiary structure at its promoter. iScience 23: 100835. [PMC free article: PMC7033639] [PubMed: 32000125]
    787.
    Azzalin C.M., Reichenbach P., Khoriauli L., Giulotto E. and Lingner J. (2007) Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318: 798–801. [PubMed: 17916692]
    788.
    Schoeftner S. and Blasco M.A. (2008) Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nature Cell Biology 10: 228–236. [PubMed: 18157120]
    789.
    Xu Y., Kimura T. and Komiyama M. (2008) Human telomere RNA and DNA form an intermolecular G-quadruplex. Nucleic Acids Symposium Series (Oxford) 52: 169–170. [PubMed: 18776307]
    790.
    Montero J.J. et al. (2018) TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin. Nature Communications 9: 1548. [PMC free article: PMC5906467] [PubMed: 29670078]
    791.
    Chu H.-P. et al. (2017) TERRA RNA antagonizes ATRX and protects telomeres. Cell 170: 86–101. [PMC free article: PMC5552367] [PubMed: 28666128]
    792.
    Marión R.M. et al. (2019) TERRA regulate the transcriptional landscape of pluripotent cells through TRF1-dependent recruitment of PRC2. eLife 8: e44656. [PMC free article: PMC6701927] [PubMed: 31426913]
    793.
    Silva B., Arora R., Bione S. and Azzalin C.M. (2021) TERRA transcription destabilizes telomere integrity to initiate break-induced replication in human ALT cells. Nature Communications 12: 3760. [PMC free article: PMC8213692] [PubMed: 34145295]
    794.
    Graf M. et al. (2017) Telomere length determines TERRA and R-loop regulation through the cell cycle. Cell 170: 72–85. [PubMed: 28666126]
    795.
    Kwapisz M. and Morillon A. (2020) Subtelomeric transcription and its regulation. Journal of Molecular Biology 432: 4199–4219. [PMC free article: PMC7374410] [PubMed: 32035903]
    796.
    Mattick J.S., Amaral P.P., Dinger M.E., Mercer T.R. and Mehler M.F. (2009) RNA regulation of epigenetic processes. BioEssays 31: 51–59. [PubMed: 19154003]
    797.
    Koziol M.J. and Rinn J.L. (2010) RNA traffic control of chromatin complexes. Current Opinion in Genetics and Development 20: 142–148. [PMC free article: PMC2895502] [PubMed: 20362426]
    798.
    Mattick J.S. and Gagen M.J. (2001) The evolution of controlled multitasked gene networks: The role of introns and other noncoding RNAs in the development of complex organisms. Molecular Biology and Evolution 18: 1611–1630. [PubMed: 11504843]
    799.
    Lee J.T. (2012) Epigenetic regulation by long noncoding RNAs. Science 338: 1435–1439. [PubMed: 23239728]
    800.
    Mercer T.R. and Mattick J.S. (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nature Structural & Molecular Biology 20: 300–307. [PubMed: 23463315]
    801.
    Bernstein E. et al. (2006) Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. Molecular Cell Biology 26: 2560–2569. [PMC free article: PMC1430336] [PubMed: 16537902]
    802.
    Yu W. et al. (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451: 202–206. [PMC free article: PMC2743558] [PubMed: 18185590]
    803.
    Yap K.L. et al. (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Molecular Cell 38: 662–674. [PMC free article: PMC2886305] [PubMed: 20541999]
    804.
    Kotake Y. et al. (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30: 1956–1962. [PMC free article: PMC3230933] [PubMed: 21151178]
    805.
    Alfeghaly C. et al. (2021) Implication of repeat insertion domains in the trans-activity of the long non-coding RNA ANRIL. Nucleic Acids Research 49: 4954–4970. [PMC free article: PMC8136789] [PubMed: 33872355]
    806.
    Bae E., Calhoun V.C., Levine M., Lewis E.B. and Drewell R.A. (2002) Characterization of the intergenic RNA profile at abdominal-A and abdominal-B in the Drosophila bithorax complex. Proceedings of the National Academy of Sciences USA 99: 16847–16852. [PMC free article: PMC139232] [PubMed: 12481037]
    807.
    Bender W. and Fitzgerald D.P. (2002) Transcription activates repressed domains in the Drosophila bithorax complex. Development 129: 4923–4930. [PubMed: 12397101]
    808.
    Drewell R.A., Bae E., Burr J. and Lewis E.B. (2002) Transcription defines the embryonic domains of cis-regulatory activity at the Drosophila bithorax complex. Proceedings of the National Academy of Sciences USA 99: 16853–16858. [PMC free article: PMC139233] [PubMed: 12477928]
    809.
    Hogga I. and Karch F. (2002) Transcription through the iab-7 cis-regulatory domain of the bithorax complex interferes with maintenance of Polycomb-mediated silencing. Development 129: 4915–4922. [PubMed: 12397100]
    810.
    Rank G., Prestel M. and Paro R. (2002) Transcription through intergenic chromosomal memory elements of the Drosophila bithorax complex correlates with an epigenetic switch. Molecular and Cellular Biology 22: 8026–8034. [PMC free article: PMC134728] [PubMed: 12391168]
    811.
    Schmitt S., Prestel M. and Paro R. (2005) Intergenic transcription through a polycomb group response element counteracts silencing. Genes & Development 19: 697–708. [PMC free article: PMC1065723] [PubMed: 15741315]
    812.
    Lempradl A. and Ringrose L. (2008) How does noncoding transcription regulate Hox genes? BioEssays 30: 110–121. [PubMed: 18200528]
    813.
    Khalil A.M. et al. (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proceedings of the National Academy of Sciences USA 106: 11667–11672. [PMC free article: PMC2704857] [PubMed: 19571010]
    814.
    Zhao J. et al. (2010) Genome-wide identification of polycomb-associated RNAs by RIP-seq. Molecular Cell 40: 939–953. [PMC free article: PMC3021903] [PubMed: 21172659]
    815.
    Davidovich C., Zheng L., Goodrich K.J. and Cech T.R. (2013) Promiscuous RNA binding by Polycomb repressive complex 2. Nature Structural & Molecular Biology 20: 1250–1257. [PMC free article: PMC3823624] [PubMed: 24077223]
    816.
    Tsai M.C. et al. (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329: 689–693. [PMC free article: PMC2967777] [PubMed: 20616235]
    817.
    Gupta R.A. et al. (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464: 1071–1076. [PMC free article: PMC3049919] [PubMed: 20393566]
    818.
    Spitale R.C., Tsai M.C. and Chang H.Y. (2011) RNA templating the epigenome: Long noncoding RNAs as molecular scaffolds. Epigenetics 6: 539–543. [PMC free article: PMC3230545] [PubMed: 21393997]
    819.
    Guttman M. and Rinn J.L. (2012) Modular regulatory principles of large non-coding RNAs. Nature 482: 339–346. [PMC free article: PMC4197003] [PubMed: 22337053]
    820.
    Wierzbicki A.T., Blevins T. and Swiezewski S. (2021) Long noncoding RNAs in plants. Annual Review of Plant Biology 72: 245–271. [PubMed: 33752440]
    821.
    Ietswaart R., Wu Z. and Dean C. (2012) Flowering time control: Another window to the connection between antisense RNA and chromatin. Trends in Genetics 28: 445–453. [PubMed: 22785023]
    822.
    Swiezewski S., Liu F., Magusin A. and Dean C. (2009) Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target. Nature 462: 799–802. [PubMed: 20010688]
    823.
    Heo J.B. and Sung S. (2011) Vernalization-mediated epigenetic silencing by a long intronic noncoding RNA. Science 331: 76–79. [PubMed: 21127216]
    824.
    Sun Q., Csorba T., Skourti-Stathaki K., Proudfoot N.J. and Dean C. (2013) R-Loop stabilization represses antisense transcription at the Arabidopsis FLC locus. Science 340: 619–621. [PMC free article: PMC5144995] [PubMed: 23641115]
    825.
    Csorba T., Questa J.I., Sun Q. and Dean C. (2014) Antisense COOLAIR mediates the coordinated switching of chromatin states at FLC during vernalization. Proceedings of the National Academy of Sciences USA 111: 16160–16165. [PMC free article: PMC4234544] [PubMed: 25349421]
    826.
    Zhu D., Rosa S. and Dean C. (2015) Nuclear organization changes and the epigenetic silencing of FLC during vernalization. Journal of Molecular Biology 427: 659–669. [PubMed: 25180639]
    827.
    Hawkes E.J. et al. (2016) COOLAIR antisense RNAs form evolutionarily conserved elaborate secondary structures. Cell Reports 16: 3087–3096. [PMC free article: PMC6827332] [PubMed: 27653675]
    828.
    Kim D.-H., Xi Y. and Sung S. (2017) Modular function of long noncoding RNA, COLDAIR, in the vernalization response. PLOS Genetics 13: e1006939. [PMC free article: PMC5552341] [PubMed: 28759577]
    829.
    Kim D.H. and Sung S. (2017) Vernalization-triggered intragenic chromatin loop formation by long noncoding RNAs. Developmental Cell 40: 302–312. [PMC free article: PMC5303624] [PubMed: 28132848]
    830.
    Yang H. et al. (2017) Distinct phases of Polycomb silencing to hold epigenetic memory of cold in Arabidopsis. Science 357: 1142–1145. [PubMed: 28818969]
    831.
    Whittaker C. and Dean C. (2017) The FLC locus: A platform for discoveries in epigenetics and adaptation. Annual Review of Cell and Developmental Biology 33: 555–575. [PubMed: 28693387]
    832.
    Tian Y. et al. (2019) PRC2 recruitment and H3K27me3 deposition at FLC require FCA binding of COOLAIR. Science Advances 5: eaau7246. [PMC free article: PMC6482009] [PubMed: 31032401]
    833.
    Fang X. et al. (2019) Arabidopsis FLL2 promotes liquid–liquid phase separation of polyadenylation complexes. Nature 569: 265–269. [PMC free article: PMC6625965] [PubMed: 31043738]
    834.
    Xu C. et al. (2021) R-loop resolution promotes co-transcriptional chromatin silencing. Nature Communications 12: 1790. [PMC free article: PMC7979926] [PubMed: 33741984]
    835.
    Zhu P., Lister C. and Dean C. (2021) Cold-induced Arabidopsis FRIGIDA nuclear condensates for FLC repression. Nature 599: 657–661. [PMC free article: PMC8612926] [PubMed: 34732891]
    836.
    Rosa S., Duncan S. and Dean C. (2016) Mutually exclusive sense–antisense transcription at FLC facilitates environmentally induced gene repression. Nature Communications 7: 13031. [PMC free article: PMC5059766] [PubMed: 27713408]
    837.
    Li P., Tao Z. and Dean C. (2015) Phenotypic evolution through variation in splicing of the noncoding RNA COOLAIR. Genes & Development 29: 696–701. [PMC free article: PMC4387712] [PubMed: 25805848]
    838.
    Berry S. and Dean C. (2015) Environmental perception and epigenetic memory: Mechanistic insight through FLC. Plant Journal 83: 133–148. [PMC free article: PMC4691321] [PubMed: 25929799]
    839.
    Jin Y., Ivanov M., Dittrich A.N., Nelson A.D.L. and Marquardt S. (2021) A trans-acting long non-coding RNA represses flowering in Arabidopsis. bioRxiv: 2021.11.15.468639.
    840.
    Chen Y. et al. (2021) Hovlinc is a recently evolved class of ribozyme found in human lncRNA. Nature Chemical Biology 17: 601–607. [PubMed: 33753927]
    841.
    Shen S. et al. (2021) circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1. Annals of the Rheumatic Diseases 80: 1209–1219. [PMC free article: PMC8372377] [PubMed: 34039624]
    842.
    Banks I.R., Zhang Y., Wiggins B.E., Heck G.R. and Ivashuta S. (2012) RNA decoys: An emerging component of plant regulatory networks? Plant Signaling & Behavior 7: 1188–1193. [PMC free article: PMC3489658] [PubMed: 22899065]
    843.
    Thomson D.W. and Dinger M.E. (2016) Endogenous microRNA sponges: Evidence and controversy. Nature Reviews Genetics 17: 272–283. [PubMed: 27040487]
    844.
    Nowak R. (1994) Mining treasures from ‘junk DNA’. Science 263: 608–610. [PubMed: 7508142]
    845.
    Pennisi E. (2010) Shining a light on the genome’s ‘dark matter’. Science 330: 1614. [PubMed: 21163986]
    846.
    Lee H., Zhang Z. and Krause H.M. (2019) Long noncoding RNAs and repetitive elements: Junk or intimate evolutionary partners? Trends in Genetics 35: 892–902. [PubMed: 31662190]
    847.
    Scherer S.W. et al. (2003) Human chromosome 7: DNA sequence and biology. Science 300: 767–772. [PMC free article: PMC2882961] [PubMed: 12690205]
    848.
    Duan Y., Zhao M., Jiang M., Li Z. and Ni C. (2020) LINC02476 promotes the malignant phenotype of hepatocellular carcinoma by sponging miR-497 and increasing HMGA2 expression. OncoTargets and Therapy 13: 2701–2710. [PMC free article: PMC7132004] [PubMed: 32280244]
    849.
    Cech T.R. and Steitz J.A. (2014) The noncoding RNA revolution - trashing old rules to forge new ones. Cell 157: 77–94. [PubMed: 24679528]
    850.
    Stent G.S. (1972) Prematurity and uniqueness in scientific discovery. Scientific American 227: 84–93. [PubMed: 4564019]

    Chapter 14

    1.
    Waddington C.H. (1942) Canalization of development and the inheritance of acquired characters. Nature 150: 563–565.
    2.
    Waddington C.H. (1957) The Strategy of the Genes: A Discussion of Some Aspects of Theoretical Biology (George Allen and Unwin, New York).
    3.
    Waddington C.H. (1966) Principles of Development and Differentiation (Macmillan, New York).
    4.
    Robertson A. (1977) Conrad Hal Waddington, 8 November 1905–26 September 1975. Biographical Memoirs of Fellows of the Royal Society 23: 575–622. [PubMed: 11615737]
    5.
    Allen M. (2015) Compelled by the diagram: Thinking through C. H. Waddington’s epigenetic landscape. Contemporaneity: Historical Presence in Visual Culture 4: 119–142.
    6.
    Saksouk N., Simboeck E. and Déjardin J. (2015) Constitutive heterochromatin formation and transcription in mammals. Epigenetics & Chromatin 8: 3. [PMC free article: PMC4363358] [PubMed: 25788984]
    7.
    Żylicz J.J. and Heard E. (2020) Molecular mechanisms of facultative heterochromatin formation: An X-chromosome perspective. Annual Review of Biochemistry 89: 255–282. [PubMed: 32259458]
    8.
    Dixon J.R. et al. (2015) Chromatin architecture reorganization during stem cell differentiation. Nature 518: 331–336. [PMC free article: PMC4515363] [PubMed: 25693564]
    9.
    Maeda R.K. and Karch F. (2015) The open for business model of the bithorax complex in Drosophila. Chromosoma 124: 293–307. [PMC free article: PMC4548009] [PubMed: 26067031]
    10.
    Olins A.L. and Olins D.E. (1974) Spheroid chromatin units (ν bodies). Science 183: 330–332. [PubMed: 4128918]
    11.
    Kornberg R.D. and Thomas J.O. (1974) Chromatin structure; oligomers of the histones. Science 184: 865–868. [PubMed: 4825888]
    12.
    Kornberg R.D. (1974) Chromatin structure: A repeating unit of histones and DNA. Science 184: 868–871. [PubMed: 4825889]
    13.
    Woodcock C.L.F., Safer J.P. and Stanchfield J.E. (1976) Structural repeating units in chromatin: I. Evidence for their general occurrence. Experimental Cell Research 97: 101–110. [PubMed: 812708]
    14.
    Olins D.E. and Olins A.L. (2003) Chromatin history: Our view from the bridge. Nature Reviews Molecular Cell Biology 4: 809–814. [PubMed: 14570061]
    15.
    Allfrey V.G. and Mirsky A.E. (1964) Structural modifications of histones and their possible role in the regulation of RNA synthesis. Science 144: 559. [PubMed: 17836360]
    16.
    Allfrey V.G., Faulkner R. and Mirsky A.E. (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proceedings of the National Academy of Sciences USA 51: 786–794. [PMC free article: PMC300163] [PubMed: 14172992]
    17.
    Allfrey V.G., Pogo B.G., Littau V.C., Gershey E.L. and Mirsky A.E. (1968) Histone acetylation in insect chromosomes. Science 159: 314–316. [PubMed: 5634500]
    18.
    Gaspar-Maia A., Alajem A., Meshorer E. and Ramalho-Santos M. (2011) Open chromatin in pluripotency and reprogramming. Nature Reviews Molecular Cell Biology 12: 36–47. [PMC free article: PMC3891572] [PubMed: 21179060]
    19.
    Finch J.T. and Klug A. (1976) Solenoidal model for superstructure in chromatin. Proceedings of the National Academy of Sciences USA 73: 1897–1901. [PMC free article: PMC430414] [PubMed: 1064861]
    20.
    Tremethick D.J. (2007) Higher-order structures of chromatin: The elusive 30 nm fiber. Cell 128: 651–654. [PubMed: 17320503]
    21.
    Grigoryev S.A. and Woodcock C.L. (2012) Chromatin organization — the 30nm fiber. Experimental Cell Research 318: 1448–1455. [PubMed: 22394510]
    22.
    Krietenstein N. and Rando O.J. (2020) Mesoscale organization of the chromatin fiber. Current Opinion in Genetics and Development 61: 32–36. [PubMed: 32305817]
    23.
    Paulson J.R. and Laemmli U.K. (1977) The structure of histone-depleted metaphase chromosomes. Cell 12: 817–828. [PubMed: 922894]
    24.
    Marston A.L. and Amon A. (2004) Meiosis: Cell-cycle controls shuffle and deal. Nature Reviews Molecular Cell Biology 5: 983–997. [PubMed: 15573136]
    25.
    McIntosh J.R. (2016) Mitosis. Cold Spring Harbor Perspectives in Biology 8: a023218. [PMC free article: PMC5008068] [PubMed: 27587616]
    26.
    Fitz-James M.H. et al. (2020) Large domains of heterochromatin direct the formation of short mitotic chromosome loops. eLife 9: e57212. [PMC free article: PMC7515631] [PubMed: 32915140]
    27.
    Bannister A.J. and Kouzarides T. (2011) Regulation of chromatin by histone modifications. Cell Research 21: 381–395. [PMC free article: PMC3193420] [PubMed: 21321607]
    28.
    Liu J., Ali M. and Zhou Q. (2020) Establishment and evolution of heterochromatin. Annals of the New York Academy of Sciences 1476: 59–77. [PMC free article: PMC7586837] [PubMed: 32017156]
    29.
    Pederson T. and Bhorjee J.S. (1979) Evidence for a role of RNA in eukaryotic chromosome structure. Metabolically stable, small nuclear RNA species are covalently linked to chromosomal DNA in HeLa cells. Journal of Molecular Biology 128: 451–480. [PubMed: 571474]
    30.
    Schubert T. et al. (2012) Df31 protein and snoRNAs maintain accessible higher-order structures of chromatin. Molecular Cell 48: 434–444. [PubMed: 23022379]
    31.
    Schwartz U. et al. (2019) Characterizing the nuclease accessibility of DNA in human cells to map higher order structures of chromatin. Nucleic Acids Research 47: 1239–1254. [PMC free article: PMC6379673] [PubMed: 30496478]
    32.
    Caspersson T., Zech L. and Johansson C. (1970) Differential binding of alkylating fluorochromes in human chromosomes. Experimental Cell Research 60: 315–319. [PubMed: 5422961]
    33.
    Korenberg J.R. and Rykowski M.C. (1988) Human genome organization: Alu, LINES, and the molecular structure of metaphase chromosome bands. Cell 53: 391–400. [PubMed: 3365767]
    34.
    Bernardi G. (1989) The isochore organization of the human genome. Annual Review of Genetics 23: 637–659. [PubMed: 2694946]
    35.
    Craig J.M. and Bickmore W.A. (1993) Genes and genomes: Chromosome bands – flavours to savour. BioEssays 15: 349–354. [PubMed: 8343145]
    36.
    Craig J.M. and Bickmore W.A. (1994) The distribution of CpG islands in mammalian chromosomes. Nature Genetics 7: 376–382. [PubMed: 7920655]
    37.
    Versteeg R. et al. (2003) The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. Genome Research 13: 1998–2004. [PMC free article: PMC403669] [PubMed: 12915492]
    38.
    Zhimulev I.F., Belyaeva E.S., Vatolina T.Y. and Demakov S.A. (2012) Banding patterns in Drosophila melanogaster polytene chromosomes correlate with DNA-binding protein occupancy. BioEssays 34: 498–508. [PubMed: 22419120]
    39.
    Bernardi G. (2015) Chromosome architecture and genome organization. PLOS ONE 10: e0143739. [PMC free article: PMC4664426] [PubMed: 26619076]
    40.
    Bickmore W.A. (2019) Patterns in the genome. Heredity 123: 50–57. [PMC free article: PMC6781130] [PubMed: 31189906]
    41.
    Lu J.Y. et al. (2021) Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome. Cell Research 31: 613–630. [PMC free article: PMC8169921] [PubMed: 33514913]
    42.
    Lu J.Y. et al. (2020) Genomic repeats categorize genes with distinct functions for orchestrated regulation. Cell Reports 30: 3296–3311. [PMC free article: PMC7195444] [PubMed: 32160538]
    43.
    Croft J.A. et al. (1999) Differences in the localization and morphology of chromosomes in the human nucleus. Journal of Cell Biology 145: 1119–1131. [PMC free article: PMC2133153] [PubMed: 10366586]
    44.
    Cremer T. and Cremer C. (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Reviews Genetics 2: 292–301. [PubMed: 11283701]
    45.
    Tanabe H. et al. (2002) Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proceedings of the National Academy of Sciences USA 99: 4424–4429. [PMC free article: PMC123664] [PubMed: 11930003]
    46.
    Bolzer A. et al. (2005) Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLOS Biology 3: e157. [PMC free article: PMC1084335] [PubMed: 15839726]
    47.
    Cremer T. and Cremer M. (2010) Chromosome territories. Cold Spring Harbor Perspectives in Biology 2: a003889. [PMC free article: PMC2829961] [PubMed: 20300217]
    48.
    Stevens T.J. et al. (2017) 3D structures of individual mammalian genomes studied by single-cell Hi-C. Nature 544: 59–64. [PMC free article: PMC5385134] [PubMed: 28289288]
    49.
    Rabi C. (1885) On cell division. Morphological Yearbook 10: 214–330.
    50.
    Boveri T. (1909) Die Blastomerenkerne von Ascaris megalocephala und die Theorie der Chromosomenindividualität. Archiv für Zellforschung 3: 181–268.
    51.
    Comings D.E. (1980) Arrangement of chromatin in the nucleus. Human Genetics 53: 131–143. [PubMed: 6987157]
    52.
    Albiez H. et al. (2006) Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks. Chromosome Research 14: 707–733. [PubMed: 17115328]
    53.
    Küpper K. et al. (2007) Radial chromatin positioning is shaped by local gene density, not by gene expression. Chromosoma 116: 285–306. [PMC free article: PMC2688818] [PubMed: 17333233]
    54.
    Harr J.C., Gonzalez-Sandoval A. and Gasser S.M. (2016) Histones and histone modifications in perinuclear chromatin anchoring: From yeast to man. EMBO Reports 17: 139–155. [PMC free article: PMC4783997] [PubMed: 26792937]
    55.
    Hu B. et al. (2019) Plant lamin-like proteins mediate chromatin tethering at the nuclear periphery. Genome Biology 20: 87. [PMC free article: PMC6492433] [PubMed: 31039799]
    56.
    Girelli G. et al. (2020) GPSeq reveals the radial organization of chromatin in the cell nucleus. Nature Biotechnology 38: 1184–1193. [PMC free article: PMC7610410] [PubMed: 32451505]
    57.
    Lieberman-Aiden E. et al. (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326: 289–293. [PMC free article: PMC2858594] [PubMed: 19815776]
    58.
    Dong P. et al. (2017) 3D chromatin architecture of large plant genomes determined by local A/B compartments. Molecular Plant 10: 1497–1509. [PubMed: 29175436]
    59.
    Dekker J., Rippe K., Dekker M. and Kleckner N. (2002) Capturing chromosome conformation. Science 295: 1306–1311. [PubMed: 11847345]
    60.
    Dixon J.R. et al. (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485: 376–380. [PMC free article: PMC3356448] [PubMed: 22495300]
    61.
    Nora E.P., Dekker J. and Heard E. (2013) Segmental folding of chromosomes: A basis for structural and regulatory chromosomal neighborhoods? BioEssays 35: 818–828. [PMC free article: PMC3874840] [PubMed: 23832846]
    62.
    Gibcus J.H. and Dekker J. (2013) The hierarchy of the 3D genome. Molecular Cell 49: 773–782. [PMC free article: PMC3741673] [PubMed: 23473598]
    63.
    Pombo A. and Dillon N. (2015) Three-dimensional genome architecture: Players and mechanisms. Nature Reviews Molecular Cell Biology 16: 245–257. [PubMed: 25757416]
    64.
    Lupiáñez D.G. et al. (2015) Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161: 1012–1025. [PMC free article: PMC4791538] [PubMed: 25959774]
    65.
    Dekker J. and Heard E. (2015) Structural and functional diversity of topologically associating domains. FEBS Letters 589: 2877–2884. [PMC free article: PMC4598308] [PubMed: 26348399]
    66.
    Dekker J. and Mirny L. (2016) The 3D genome as moderator of chromosomal communication. Cell 164: 1110–1121. [PMC free article: PMC4788811] [PubMed: 26967279]
    67.
    Fortin J.-P. and Hansen K.D. (2015) Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data. Genome Biology 16: 180. [PMC free article: PMC4574526] [PubMed: 26316348]
    68.
    Rowley M.J. et al. (2017) Evolutionarily conserved principles predict 3D chromatin organization. Molecular Cell 67: 837–852. [PMC free article: PMC5591081] [PubMed: 28826674]
    69.
    Falk M. et al. (2019) Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature 570: 395–399. [PMC free article: PMC7206897] [PubMed: 31168090]
    70.
    Krietenstein N. et al. (2020) Ultrastructural details of mammalian chromosome architecture. Molecular Cell 78: 554–565. [PMC free article: PMC7222625] [PubMed: 32213324]
    71.
    Grubert F. et al. (2020) Landscape of cohesin-mediated chromatin loops in the human genome. Nature 583: 737–743. [PMC free article: PMC7410831] [PubMed: 32728247]
    72.
    Chadwick B.P. (2008) DXZ4 chromatin adopts an opposing conformation to that of the surrounding chromosome and acquires a novel inactive X-specific role involving CTCF and antisense transcripts. Genome Research 18: 1259–1269. [PMC free article: PMC2493436] [PubMed: 18456864]
    73.
    Giorgetti L. et al. (2016) Structural organization of the inactive X chromosome in the mouse. Nature 535: 575–579. [PMC free article: PMC5443622] [PubMed: 27437574]
    74.
    Bonora G. et al. (2018) Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome. Nature Communications 9: 1445. [PMC free article: PMC5899087] [PubMed: 29654302]
    75.
    Andergassen D. et al. (2019) In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation. eLife 8: e47214. [PMC free article: PMC6860989] [PubMed: 31738164]
    76.
    Nora E.P. et al. (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485: 381–385. [PMC free article: PMC3555144] [PubMed: 22495304]
    77.
    van Bemmel J.G. et al. (2019) The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist. Nature Genetics 51: 1024–1034. [PMC free article: PMC6551226] [PubMed: 31133748]
    78.
    Polymenidou M. (2018) The RNA face of phase separation. Science 360: 859–860. [PubMed: 29798872]
    79.
    Sabari B.R. et al. (2018) Coactivator condensation at super-enhancers links phase separation and gene control. Science 361: eaar3958. [PMC free article: PMC6092193] [PubMed: 29930091]
    80.
    Berry J., Weber S.C., Vaidya N., Haataja M. and Brangwynne C.P. (2015) RNA transcription modulates phase transition-driven nuclear body assembly. Proceedings of the National Academy of Sciences USA 112: E5237–45. [PMC free article: PMC4586886] [PubMed: 26351690]
    81.
    Sawyer I.A. and Dundr M. (2017) Chromatin loops and causality loops: The influence of RNA upon spatial nuclear architecture. Chromosoma 126: 541–557. [PubMed: 28593374]
    82.
    Strom A.R. et al. (2017) Phase separation drives heterochromatin domain formation. Nature 547: 241–245. [PMC free article: PMC6022742] [PubMed: 28636597]
    83.
    Zenk F. et al. (2021) HP1 drives de novo 3D genome reorganization in early Drosophila embryos. Nature 593: 613–630. [PMC free article: PMC8116211] [PubMed: 33854237]
    84.
    Bonev B. et al. (2017) Multiscale 3D genome rewiring during mouse neural development. Cell 171: 557–572. [PMC free article: PMC5651218] [PubMed: 29053968]
    85.
    Ulianov S.V. et al. (2016) Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains. Genome Research 26: 70–84. [PMC free article: PMC4691752] [PubMed: 26518482]
    86.
    Peters J.-M., Tedeschi A. and Schmitz J. (2008) The cohesin complex and its roles in chromosome biology. Genes & Development 22: 3089–3114. [PubMed: 19056890]
    87.
    Kim S., Yu N.-K. and Kaang B.-K. (2015) CTCF as a multifunctional protein in genome regulation and gene expression. Experimental & Molecular Medicine 47: e166. [PMC free article: PMC4491725] [PubMed: 26045254]
    88.
    Sanborn A.L. et al. (2015) Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proceedings of the National Academy of Sciences USA 112: E6456–65. [PMC free article: PMC4664323] [PubMed: 26499245]
    89.
    Wutz G. et al. (2017) Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins. EMBO Journal 36: 3573–3599. [PMC free article: PMC5730888] [PubMed: 29217591]
    90.
    Vian L. et al. (2018) The energetics and physiological impact of cohesin extrusion. Cell 173: 1165–1178. [PMC free article: PMC6065110] [PubMed: 29706548]
    91.
    Pugacheva E.M. et al. (2020) CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention. Proceedings of the National Academy of Sciences USA 117: 2020–2031. [PMC free article: PMC6995019] [PubMed: 31937660]
    92.
    Ryu J.-K. et al. (2021) Bridging-induced phase separation induced by cohesin SMC protein complexes. Science Advances 7: eabe5905. [PMC free article: PMC7875533] [PubMed: 33568486]
    93.
    Diehl A.G., Ouyang N. and Boyle A.P. (2020) Transposable elements contribute to cell and species-specific chromatin looping and gene regulation in mammalian genomes. Nature Communications 11: 1796. [PMC free article: PMC7156512] [PubMed: 32286261]
    94.
    Nanavaty V. et al. (2020) DNA methylation regulates alternative polyadenylation via CTCF and the cohesin complex. Molecular Cell 78: 752–764. [PMC free article: PMC7245569] [PubMed: 32333838]
    95.
    Mukhopadhyay R. et al. (2004) The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genome-wide. Genome Research 14: 1594–1602. [PMC free article: PMC509268] [PubMed: 15256511]
    96.
    Wang H. et al. (2012) Widespread plasticity in CTCF occupancy linked to DNA methylation. Genome Research 22: 1680–1688. [PMC free article: PMC3431485] [PubMed: 22955980]
    97.
    Maurano M.T. et al. (2015) Role of DNA methylation in modulating transcription factor occupancy. Cell Reports 12: 1184–1195. [PubMed: 26257180]
    98.
    Hashimoto H. et al. (2017) Structural basis for the versatile and methylation-dependent binding of CTCF to DNA. Molecular Cell 66: 711–720. [PMC free article: PMC5542067] [PubMed: 28529057]
    99.
    Wiehle L. et al. (2019) DNA (de)methylation in embryonic stem cells controls CTCF-dependent chromatin boundaries. Genome Research 29: 750–761. [PMC free article: PMC6499307] [PubMed: 30948436]
    100.
    Damaschke N.A. et al. (2020) CTCF loss mediates unique DNA hypermethylation landscapes in human cancers. Clinical Epigenetics 12: 80. [PMC free article: PMC7275597] [PubMed: 32503656]
    101.
    Guelen L. et al. (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453: 948–951. [PubMed: 18463634]
    102.
    Dobrzynska A., Gonzalo S., Shanahan C. and Askjaer P. (2016) The nuclear lamina in health and disease. Nucleus 7: 233–248. [PMC free article: PMC4991244] [PubMed: 27158763]
    103.
    Costantini M., Cammarano R. and Bernardi G. (2009) The evolution of isochore patterns in vertebrate genomes. BMC Genomics 10: 146. [PMC free article: PMC2678159] [PubMed: 19344507]
    104.
    Bernardi G. (2018) The formation of chromatin domains involves a primary step based on the 3-D structure of DNA. Scientific Reports 8: 17821. [PMC free article: PMC6292937] [PubMed: 30546050]
    105.
    Yunis J.J. (1981) Mid-prophase human chromosomes. The attainment of 2000 bands. Human Genetics 56: 293–298. [PubMed: 7239513]
    106.
    Drouin R. and Richer C.-L. (1989) High-resolution R-banding at the 1250-band level. II. Schematic representation and nomenclature of human RBG-banded chromosomes. Genome 32: 425–439. [PubMed: 2744449]
    107.
    Eagen K.P., Hartl T.A. and Kornberg R.D. (2015) Stable chromosome condensation revealed by chromosome conformation capture. Cell 163: 934–946. [PMC free article: PMC4639323] [PubMed: 26544940]
    108.
    Macgregor H.C. (2012) Chromomeres revisited. Chromosome Research 20: 911–924. [PubMed: 22956230]
    109.
    Eagen K.P. (2018) Principles of chromosome architecture revealed by Hi-C. Trends in Biochemical Sciences 43: 469–478. [PMC free article: PMC6028237] [PubMed: 29685368]
    110.
    Beagan J.A. and Phillips-Cremins J.E. (2020) On the existence and functionality of topologically associating domains. Nature Genetics 52: 8–16. [PMC free article: PMC7567612] [PubMed: 31925403]
    111.
    Pope B.D. et al. (2014) Topologically associating domains are stable units of replication-timing regulation. Nature 515: 402–405. [PMC free article: PMC4251741] [PubMed: 25409831]
    112.
    Dixon J.R., Gorkin D.U. and Ren B. (2016) Chromatin domains: The unit of chromosome organization. Molecular Cell 62: 668–680. [PMC free article: PMC5371509] [PubMed: 27259200]
    113.
    Harmston N. et al. (2017) Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation. Nature Communications 8: 441. [PMC free article: PMC5585340] [PubMed: 28874668]
    114.
    Yu M. and Ren B. (2017) The three-dimensional organization of mammalian genomes. Annual Review of Cell and Developmental Biology 33: 265–289. [PMC free article: PMC5837811] [PubMed: 28783961]
    115.
    Winick-Ng W. et al. (2021) Cell-type specialization is encoded by specific chromatin topologies. Nature 599: 684–691. [PMC free article: PMC8612935] [PubMed: 34789882]
    116.
    Symmons O. et al. (2014) Functional and topological characteristics of mammalian regulatory domains. Genome Research 24: 390–400. [PMC free article: PMC3941104] [PubMed: 24398455]
    117.
    Zhang Y. et al. (2019) Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. Nature Genetics 51: 1380–1388. [PMC free article: PMC6722002] [PubMed: 31427791]
    118.
    Shuaib M. et al. (2019) Nuclear AGO1 regulates gene expression by affecting chromatin architecture in human cells. Cell Systems 9: 446–458. [PubMed: 31629687]
    119.
    Lonfat N. and Duboule D. (2015) Structure, function and evolution of topologically associating domains (TADs) at HOX loci. FEBS Letters 589: 2869–2876. [PubMed: 25913784]
    120.
    Le Dily F. and Beato M. (2015) TADs as modular and dynamic units for gene regulation by hormones. FEBS Letters 589: 2885–2892. [PubMed: 26012375]
    121.
    Le Dily F. and Beato M. (2018) Signaling by steroid hormones in the 3D nuclear space. International Journal of Molecular Sciences 19: 306. [PMC free article: PMC5855546] [PubMed: 29360755]
    122.
    Beagan J.A. et al. (2020) Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression. Nature Neuroscience 23: 707–717. [PMC free article: PMC7558717] [PubMed: 32451484]
    123.
    Arnould C. et al. (2021) Loop extrusion as a mechanism for formation of DNA damage repair foci. Nature 590: 660–665. [PMC free article: PMC7116834] [PubMed: 33597753]
    124.
    Krijger P.H.L. and de Laat W. (2016) Regulation of disease-associated gene expression in the 3D genome. Nature Reviews Molecular Cell Biology 17: 771–782. [PubMed: 27826147]
    125.
    Kaiser V.B. and Semple C.A. (2017) When TADs go bad: Chromatin structure and nuclear organisation in human disease. F1000Research 6: 314. [PMC free article: PMC5373421] [PubMed: 28408976]
    126.
    Weber B., Zicola J., Oka R. and Stam M. (2016) Plant enhancers: A call for discovery. Trends in Plant Science 21: 974–987. [PubMed: 27593567]
    127.
    Hnisz D. et al. (2013) Super-enhancers in the control of cell identity and disease. Cell 155: 934–947. [PMC free article: PMC3841062] [PubMed: 24119843]
    128.
    Shlyueva D., Stampfel G. and Stark A. (2014) Transcriptional enhancers: From properties to genome-wide predictions. Nature Reviews Genetics 15: 272–286. [PubMed: 24614317]
    129.
    Fulco C.P. et al. (2019) Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations. Nature Genetics 51: 1664–1669. [PMC free article: PMC6886585] [PubMed: 31784727]
    130.
    Arnold P.R., Wells A.D. and Li X.C. (2020) Diversity and emerging roles of enhancer RNA in regulation of gene expression and cell fate. Frontiers in Cell and Developmental Biology 7: 377. [PMC free article: PMC6971116] [PubMed: 31993419]
    131.
    Souaid C., Bloyer S. and Noordermeer D. (2018) Promoter–enhancer looping and regulatory neighborhoods: Gene regulation in the framework of topologically associating domains, in C. Lavelle and J.-M. Victor (eds.) Nuclear Architecture and Dynamics (Academic Press, New York).
    132.
    Lim B. and Levine M.S. (2021) Enhancer-promoter communication: Hubs or loops? Current Opinion in Genetics & Development 67: 5–9. [PMC free article: PMC8653970] [PubMed: 33202367]
    133.
    Zhu I., Song W., Ovcharenko I. and Landsman D. (2021) A model of active transcription hubs that unifies the roles of active promoters and enhancers. Nucleic Acids Research 49: 4493–4505. [PMC free article: PMC8096258] [PubMed: 33872375]
    134.
    Banerji J., Olson L. and Schaffner W. (1983) A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell 33: 729–740. [PubMed: 6409418]
    135.
    Kong S., Bohl D., Li C. and Tuan D. (1997) Transcription of the HS2 enhancer toward a cis-linked gene is independent of the orientation, position, and distance of the enhancer relative to the gene. Molecular and Cellular Biology 17: 3955–3965. [PMC free article: PMC232248] [PubMed: 9199330]
    136.
    Smith E. and Shilatifard A. (2014) Enhancer biology and enhanceropathies. Nature Structural & Molecular Biology 21: 210–219. [PubMed: 24599251]
    137.
    Murakawa Y. et al. (2016) Enhanced identification of transcriptional enhancers provides mechanistic insights into diseases. Trends in Genetics 32: 76–88. [PubMed: 26780995]
    138.
    Buffry A.D., Mendes C.C. and McGregor A.P. (2016) The functionality and evolution of eukaryotic transcriptional enhancers. Advances in Genetics 96: 143–206. [PubMed: 27968730]
    139.
    Rickels R. and Shilatifard A. (2018) Enhancer logic and mechanics in development and disease. Trends in Cell Biology 28: 608–630. [PubMed: 29759817]
    140.
    Schoenfelder S. and Fraser P. (2019) Long-range enhancer–promoter contacts in gene expression control. Nature Reviews Genetics 20: 437–455. [PubMed: 31086298]
    141.
    Hogness D.S. et al. (1985) Regulation and products of the Ubx domain of the bithorax complex. Cold Spring Harbor Symposia on Quantitative Biology 50: 181–194. [PubMed: 3938361]
    142.
    Akam M.E., Martinez-Arias A., Weinzierl R. and Wilde C.D. (1985) Function and expression of ultrabithorax in the Drosophila embryo. Cold Spring Harbor Symposia on Quantitative Biology 50: 195–200. [PubMed: 3868478]
    143.
    McCall K., O‘Connor M.B. and Bender W. (1994) Enhancer traps in the Drosophila bithorax complex mark parasegmental domains. Genetics 138: 387–399. [PMC free article: PMC1206157] [PubMed: 7828822]
    144.
    Banerji J., Rusconi S. and Schaffner W. (1981) Expression of a β-globin gene is enhanced by remote SV40 DNA sequences. Cell 27: 299–308. [PubMed: 6277502]
    145.
    Deniz Ö et al. (2020) Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukaemia. Nature Communications 11: 3506. [PMC free article: PMC7360734] [PubMed: 32665538]
    146.
    Li Q., Peterson K.R., Fang X. and Stamatoyannopoulos G. (2002) Locus control regions. Blood 100: 3077–3086. [PMC free article: PMC2811695] [PubMed: 12384402]
    147.
    Gillies S.D., Morrison S.L., Oi V.T. and Tonegawa S. (1983) A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 33: 717–728. [PubMed: 6409417]
    148.
    Maeda R.K. and Karch F. (2006) The ABC of the BX-C: The bithorax complex explained. Development 133: 1413–1422. [PubMed: 16556913]
    149.
    Park B.K. et al. (2004) Intergenic enhancers with distinct activities regulate Dlx gene expression in the mesenchyme of the branchial arches. Developmental Biology 268: 532–545. [PubMed: 15063187]
    150.
    Miyagi S. et al. (2006) The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon. Journal of Biological Chemistry 281: 13374–13381. [PubMed: 16547000]
    151.
    Perry M.W., Boettiger A.N. and Levine M. (2011) Multiple enhancers ensure precision of gap gene-expression patterns in the Drosophila embryo. Proceedings of the National Academy of Sciences USA 108: 13570–13575. [PMC free article: PMC3158186] [PubMed: 21825127]
    152.
    Stathopoulos A., Van Drenth M., Erives A., Markstein M. and Levine M. (2002) Whole-genome analysis of dorsal-ventral patterning in the Drosophila embryo. Cell 111: 687–701. [PubMed: 12464180]
    153.
    Ntini E. and Marsico A. (2019) Functional impacts of non-coding RNA processing on enhancer activity and target gene expression. Journal of Molecular Cell Biology 11: 868–879. [PMC free article: PMC6884709] [PubMed: 31169884]
    154.
    Halfon M.S. (2019) Studying transcriptional enhancers: The founder fallacy, validation creep, and other biases. Trends in Genetics 35: 93–103. [PMC free article: PMC6338480] [PubMed: 30553552]
    155.
    Zehnder T., Benner P. and Vingron M. (2019) Predicting enhancers in mammalian genomes using supervised hidden Markov models. BMC Bioinformatics 20: 157. [PMC free article: PMC6437899] [PubMed: 30917778]
    156.
    O’Kane C.J. and Gehring W.J. (1987) Detection in situ of genomic regulatory elements in Drosophila. Proceedings of the National Academy of Sciences USA 84: 9123–9127. [PMC free article: PMC299704] [PubMed: 2827169]
    157.
    Galloni M., Gyurkovics H., Schedl P. and Karch F. (1993) The bluetail transposon: Evidence for independent cis-regulatory domains and domain boundaries in the bithorax complex. EMBO Journal 12: 1087–1097. [PMC free article: PMC413310] [PubMed: 8384551]
    158.
    Springer P.S. (2000) Gene traps: Tools for plant development and genomics. Plant Cell 12: 1007–1020. [PMC free article: PMC149045] [PubMed: 10899970]
    159.
    Trinh L.A. and Fraser S.E. (2013) Enhancer and gene traps for molecular imaging and genetic analysis in zebrafish. Development, Growth & Differentiation 55: 434–445. [PubMed: 23565993]
    160.
    Ogryzko V.V., Schiltz R.L., Russanova V., Howard B.H. and Nakatani Y. (1996) The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87: 953–959. [PubMed: 8945521]
    161.
    Yin J.-W. and Wang G. (2014) The Mediator complex: A master coordinator of transcription and cell lineage development. Development 141: 977–987. [PubMed: 24550107]
    162.
    Allen B.L. and Taatjes D.J. (2015) The Mediator complex: A central integrator of transcription. Nature Reviews Molecular Cell Biology 16: 155–166. [PMC free article: PMC4963239] [PubMed: 25693131]
    163.
    Soutourina J. (2018) Transcription regulation by the Mediator complex. Nature Reviews Molecular Cell Biology 19: 262–274. [PubMed: 29209056]
    164.
    Lai F. et al. (2013) Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature 494: 497–501. [PMC free article: PMC4109059] [PubMed: 23417068]
    165.
    Yang Y. et al. (2016) Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster. Scientific Reports 6: 20961. [PMC free article: PMC4750091] [PubMed: 26864944]
    166.
    Bose D.A. et al. (2017) RNA binding to CBP stimulates histone acetylation and transcription. Cell 168: 135–149. [PMC free article: PMC5325706] [PubMed: 28086087]
    167.
    Heintzman N.D. et al. (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nature Genetics 39: 311–318. [PubMed: 17277777]
    168.
    Heintzman N.D. et al. (2009) Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459: 108–112. [PMC free article: PMC2910248] [PubMed: 19295514]
    169.
    Henriques T. et al. (2018) Widespread transcriptional pausing and elongation control at enhancers. Genes & Development 32: 26–41. [PMC free article: PMC5828392] [PubMed: 29378787]
    170.
    Shen Y. et al. (2012) A map of the cis-regulatory sequences in the mouse genome. Nature 488: 116–120. [PMC free article: PMC4041622] [PubMed: 22763441]
    171.
    Pradeepa M.M. et al. (2016) Histone H3 globular domain acetylation identifies a new class of enhancers. Nature Genetics 48: 681–686. [PMC free article: PMC4886833] [PubMed: 27089178]
    172.
    De Santa F. et al. (2010) A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLOS Biology 8: e1000384. [PMC free article: PMC2867938] [PubMed: 20485488]
    173.
    Wang D. et al. (2011) Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474: 390–394. [PMC free article: PMC3117022] [PubMed: 21572438]
    174.
    Wu H. et al. (2014) Tissue-specific RNA expression marks distant-acting developmental enhancers. PLOS Genetics 10: e1004610. [PMC free article: PMC4154669] [PubMed: 25188404]
    175.
    Kim T.-K., Hemberg M. and Gray J.M. (2015) Enhancer RNAs: A class of long noncoding RNAs synthesized at enhancers. Cold Spring Harbor Perspectives in Biology 7: a018622. [PMC free article: PMC4292161] [PubMed: 25561718]
    176.
    Kim Y.W., Lee S., Yun J. and Kim A. (2015) Chromatin looping and eRNA transcription precede the transcriptional activation of gene in the beta-globin locus. Bioscience Reports 35: e00179. [PMC free article: PMC4370096] [PubMed: 25588787]
    177.
    Arner E. et al. (2015) Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science 347: 1010–1014. [PMC free article: PMC4681433] [PubMed: 25678556]
    178.
    Chen H., Du G., Song X. and Li L. (2017) Non-coding transcripts from enhancers: New insights into enhancer activity and gene expression regulation. Genomics, Proteomics & Bioinformatics 15: 201–207. [PMC free article: PMC5487526] [PubMed: 28599852]
    179.
    Sartorelli V. and Lauberth S.M. (2020) Enhancer RNAs are an important regulatory layer of the epigenome. Nature Structural & Molecular Biology 27: 521–528. [PMC free article: PMC7343394] [PubMed: 32514177]
    180.
    Heidari N. et al. (2014) Genome-wide map of regulatory interactions in the human genome. Genome Research 24: 1905–1917. [PMC free article: PMC4248309] [PubMed: 25228660]
    181.
    Rubinstein M. and de Souza F.S.J. (2013) Evolution of transcriptional enhancers and animal diversity. Philosophical Transactions of the Royal Society B: Biological Sciences 368: 20130017. [PMC free article: PMC3826491] [PubMed: 24218630]
    182.
    Sebé-Pedrós A. et al. (2016) The dynamic regulatory genome of Capsaspora and the origin of animal multicellularity. Cell 165: 1224–1237. [PMC free article: PMC4877666] [PubMed: 27114036]
    183.
    Closser M. et al. (2021) An expansion of the non-coding genome and its regulatory potential underlies vertebrate neuronal diversity. Neuron 110: 70–85. [PMC free article: PMC8738133] [PubMed: 34727520]
    184.
    Glinsky G. and Barakat T.S. (2019) The evolution of Great Apes has shaped the functional enhancers’ landscape in human embryonic stem cells. Stem Cell Research 37: 101456. [PubMed: 31100635]
    185.
    Aldea D. et al. (2021) Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution. Proceedings of the National Academy of Sciences USA 118: e2021722118. [PMC free article: PMC8072367] [PubMed: 33850016]
    186.
    Prabhakar S. et al. (2008) Human-specific gain of function in a developmental enhancer. Science 321: 1346–1350. [PMC free article: PMC2658639] [PubMed: 18772437]
    187.
    Woltering J.M. and Duboule D. (2010) The origin of digits: Expression patterns versus regulatory mechanisms. Developmental Cell 18: 526–532. [PubMed: 20412768]
    188.
    Whyte W.A. et al. (2013) Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153: 307–319. [PMC free article: PMC3653129] [PubMed: 23582322]
    189.
    Parker S.C.J. et al. (2013) Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants. Proceedings of the National Academy of Sciences USA 110: 17921–17926. [PMC free article: PMC3816444] [PubMed: 24127591]
    190.
    Pott S. and Lieb J.D. (2015) What are super-enhancers? Nature Genetics 47: 8–12. [PubMed: 25547603]
    191.
    Wang X., Cairns M.J. and Yan J. (2019) Super-enhancers in transcriptional regulation and genome organization. Nucleic Acids Research 47: 11481–11496. [PMC free article: PMC7145697] [PubMed: 31724731]
    192.
    Chen H. and Liang H. (2020) A high-resolution map of human enhancer RNA loci characterizes super-enhancer activities in cancer. Cancer Cell 38: 701–715. [PMC free article: PMC7658066] [PubMed: 33007258]
    193.
    Li S. and Ovcharenko I. (2020) Enhancer jungles establish robust tissue-specific regulatory control in the human genome. Genomics 112: 2261–2270. [PMC free article: PMC7082202] [PubMed: 31887344]
    194.
    Herz H.-M. (2016) Enhancer deregulation in cancer and other diseases. BioEssays 38: 1003–1015. [PMC free article: PMC5160997] [PubMed: 27570183]
    195.
    Nott A. et al. (2019) Brain cell type-specific enhancer-promoter interactome maps and disease-risk association. Science 366: 1134–1139. [PMC free article: PMC7028213] [PubMed: 31727856]
    196.
    Nasser J. et al. (2021) Genome-wide enhancer maps link risk variants to disease genes. Nature 593: 238–243. [PMC free article: PMC9153265] [PubMed: 33828297]
    197.
    Dong X. et al. (2018) Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease. Nature Neuroscience 21: 1482–1492. [PMC free article: PMC6334654] [PubMed: 30224808]
    198.
    Ptashne M. (1988) How eukaryotic transcriptional activators work. Nature 335: 683–689. [PubMed: 3050531]
    199.
    Jindal G.A. and Farley E.K. (2021) Enhancer grammar in development, evolution, and disease: Dependencies and interplay. Developmental Cell 56: 575–587. [PMC free article: PMC8462829] [PubMed: 33689769]
    200.
    Larke M.S.C. et al. (2021) Enhancers predominantly regulate gene expression during differentiation via transcription initiation. Molecular Cell 81: 983–997. [PMC free article: PMC7612206] [PubMed: 33539786]
    201.
    Hansen A.S., Cattoglio C., Darzacq X. and Tjian R. (2018) Recent evidence that TADs and chromatin loops are dynamic structures. Nucleus 9: 20–32. [PMC free article: PMC5990973] [PubMed: 29077530]
    202.
    Postika N. et al. (2018) Boundaries mediate long-distance interactions between enhancers and promoters in the Drosophila bithorax complex. PLOS Genetics 14: e1007702. [PMC free article: PMC6306242] [PubMed: 30540750]
    203.
    Furlong E.E.M. and Levine M. (2018) Developmental enhancers and chromosome topology. Science 361: 1341–1345. [PMC free article: PMC6986801] [PubMed: 30262496]
    204.
    Ghavi-Helm Y. et al. (2019) Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression. Nature Genetics 51: 1272–1282. [PMC free article: PMC7116017] [PubMed: 31308546]
    205.
    Carullo N.V.N. et al. (2020) Enhancer RNAs predict enhancer–gene regulatory links and are critical for enhancer function in neuronal systems. Nucleic Acids Research 48: 9550–9570. [PMC free article: PMC7515708] [PubMed: 32810208]
    206.
    Benabdallah N.S. et al. (2019) Decreased enhancer-promoter proximity accompanying enhancer activation. Molecular Cell 76: 473–484. [PMC free article: PMC6838673] [PubMed: 31494034]
    207.
    Kim T.-K. et al. (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465: 182–187. [PMC free article: PMC3020079] [PubMed: 20393465]
    208.
    Li W., Notani D. and Rosenfeld M.G. (2016) Enhancers as non-coding RNA transcription units: Recent insights and future perspectives. Nature Reviews Genetics 17: 207–223. [PubMed: 26948815]
    209.
    Lewis M.W., Li S. and Franco H.L. (2019) Transcriptional control by enhancers and enhancer RNAs. Transcription 10: 171–186. [PMC free article: PMC6948965] [PubMed: 31791217]
    210.
    Azofeifa J.G. et al. (2018) Enhancer RNA profiling predicts transcription factor activity. Genome Research 28: 334–344. [PMC free article: PMC5848612] [PubMed: 29449408]
    211.
    Grossman S.R. et al. (2018) Positional specificity of different transcription factor classes within enhancers. Proceedings of the National Academy of Sciences USA 115: E7222–30. [PMC free article: PMC6065035] [PubMed: 29987030]
    212.
    Hon C.-C. et al. (2017) An atlas of human long non-coding RNAs with accurate 5′ ends. Nature 543: 199–204. [PMC free article: PMC6857182] [PubMed: 28241135]
    213.
    Soibam B. (2017) Super-lncRNAs: Identification of lncRNAs that target super-enhancers via RNA:DNA:DNA triplex formation. RNA 23: 1729–1742. [PMC free article: PMC5648039] [PubMed: 28839111]
    214.
    Mishra K. and Kanduri C. (2019) Understanding long noncoding RNA and chromatin interactions: What we know so far. Noncoding RNA 5: 54. [PMC free article: PMC6958424] [PubMed: 31817041]
    215.
    Cai Z. et al. (2020) RIC-seq for global in situ profiling of RNA–RNA spatial interactions. Nature 582: 432–437. [PubMed: 32499643]
    216.
    Thurman R.E. et al. (2012) The accessible chromatin landscape of the human genome. Nature 489: 75–82. [PMC free article: PMC3721348] [PubMed: 22955617]
    217.
    Dunham I. et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74. [PMC free article: PMC3439153] [PubMed: 22955616]
    218.
    Zhu J. et al. (2013) Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell 152: 642–654. [PMC free article: PMC3563935] [PubMed: 23333102]
    219.
    Andersson R. et al. (2014) An atlas of active enhancers across human cell types and tissues. Nature 507: 455–461. [PMC free article: PMC5215096] [PubMed: 24670763]
    220.
    Woodcock C.L. and Ghosh R.P. (2010) Chromatin higher-order structure and dynamics. Cold Spring Harbor Perspectives in Biology 2: a000596. [PMC free article: PMC2857170] [PubMed: 20452954]
    221.
    Alberts B. et al. (2002) Chromosomal DNA and Its packaging in the chromatin fiber, in Molecular Biology of the Cell, 4th edition (Garland Science, New York).
    222.
    McGhee J.D. and Felsenfeld G. (1980) Nucleosome structure. Annual Review of Biochemistry 49: 1115–1156. [PubMed: 6996562]
    223.
    Luger K., Mäder A.W., Richmond R.K., Sargent D.F. and Richmond T.J. (1997) Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389: 251–260. [PubMed: 9305837]
    224.
    Luger K. and Richmond T.J. (1998) The histone tails of the nucleosome. Current Opinion in Genetics & Development 8: 140–146. [PubMed: 9610403]
    225.
    Kornberg R.D. and Lorch Y. (1999) Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98: 285 –94. [PubMed: 10458604]
    226.
    Zhao Y.-Q., Jordan K. and Lunyak V. (2013) Epigenetics components of aging in the central nervous system. Neurotherapeutics 10: 647–663. [PMC free article: PMC3805869] [PubMed: 24132650]
    227.
    Mattiroli F. et al. (2017) Structure of histone-based chromatin in Archaea. Science 357: 609–612. [PMC free article: PMC5747315] [PubMed: 28798133]
    228.
    Attar N. et al. (2020) The histone H3-H4 tetramer is a copper reductase enzyme. Science 369: 59–64. [PMC free article: PMC7842201] [PubMed: 32631887]
    229.
    Anbar A.D. (2008) Elements and evolution. Science 322: 1481–1483. [PubMed: 19056967]
    230.
    Jamrich M., Greenleaf A.L. and Bautz E.K. (1977) Localization of RNA polymerase in polytene chromosomes of Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 74: 2079–2083. [PMC free article: PMC431078] [PubMed: 405671]
    231.
    Cutter A.R. and Hayes J.J. (2015) A brief review of nucleosome structure. FEBS Letters 589: 2914–2922. [PMC free article: PMC4598263] [PubMed: 25980611]
    232.
    Kasinsky H.E., Lewis J.D., Dacks J.B. and Ausló J. (2001) Origin of H1 linker histones. FASEB Journal 15: 34–42. [PubMed: 11149891]
    233.
    Venkatesh S. and Workman J.L. (2015) Histone exchange, chromatin structure and the regulation of transcription. Nature Reviews Molecular Cell Biology 16: 178–189. [PubMed: 25650798]
    234.
    Lai W.K.M. and Pugh B.F. (2017) Understanding nucleosome dynamics and their links to gene expression and DNA replication. Nature Reviews Molecular Cell Biology 18: 548–562. [PMC free article: PMC5831138] [PubMed: 28537572]
    235.
    Zhou K., Gaullier G. and Luger K. (2019) Nucleosome structure and dynamics are coming of age. Nature Structural & Molecular Biology 26: 3–13. [PMC free article: PMC7386248] [PubMed: 30532059]
    236.
    Carone B.R. et al. (2014) High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm. Developmental Cell 30: 11–22. [PMC free article: PMC4184102] [PubMed: 24998598]
    237.
    Jin C. and Felsenfeld G. (2007) Nucleosome stability mediated by histone variants H3.3 and H2A.Z. Genes & Development 21: 1519–1529. [PMC free article: PMC1891429] [PubMed: 17575053]
    238.
    Jin C. et al. (2009) H3.3/H2A.Z double variant-containing nucleosomes mark ‘nucleosome-free regions’ of active promoters and other regulatory regions. Nature Genetics 41: 941–945. [PMC free article: PMC3125718] [PubMed: 19633671]
    239.
    He H.H. et al. (2010) Nucleosome dynamics define transcriptional enhancers. Nature Genetics 42: 343–347. [PMC free article: PMC2932437] [PubMed: 20208536]
    240.
    Xi Y., Yao J., Chen R., Li W. and He X. (2011) Nucleosome fragility reveals novel functional states of chromatin and poises genes for activation. Genome Research 21: 718–724. [PMC free article: PMC3083088] [PubMed: 21363969]
    241.
    Voong L.N. et al. (2016) Insights into nucleosome organization in mouse embryonic stem cells through chemical mapping. Cell 167: 1555–1570. [PMC free article: PMC5135608] [PubMed: 27889238]
    242.
    Jeffers T.E. and Lieb J.D. (2017) Nucleosome fragility is associated with future transcriptional response to developmental cues and stress in C. elegans. Genome Research 27: 75–86. [PMC free article: PMC5204346] [PubMed: 27979995]
    243.
    Oruba A., Saccani S. and van Essen D. (2020) Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters. Nature Communications 11: 1075. [PMC free article: PMC7044431] [PubMed: 32103026]
    244.
    van Daal A. and Elgin S.C. (1992) A histone variant, H2AvD, is essential in Drosophila melanogaster. Molecular Biology of the Cell 3: 593–602. [PMC free article: PMC275615] [PubMed: 1498368]
    245.
    Clarkson M.J., Wells J.R.E., Gibson F., Saint R. and Tremethick D.J. (1999) Regions of variant histone His2AvD required for Drosophila development. Nature 399: 694–697. [PubMed: 10385122]
    246.
    Faast R. et al. (2001) Histone variant H2A.Z is required for early mammalian development. Current Biology 11: 1183–1187. [PubMed: 11516949]
    247.
    Ridgway P., Brown K.D., Rangasamy D., Svensson U. and Tremethick D.J. (2004) Unique residues on the H2A.Z containing nucleosome surface are important for Xenopus laevis development. Journal of Biological Chemistry 279: 43815–43820. [PubMed: 15299007]
    248.
    March-Díaz R. et al. (2008) Histone H2A.Z and homologues of components of the SWR1 complex are required to control immunity in Arabidopsis. Plant Journal 53: 475–487. [PubMed: 17988222]
    249.
    Stefanelli G. et al. (2018) Learning and age-related changes in genome-wide H2A.Z binding in the mouse hippocampus. Cell Reports 22: 1124–1131. [PMC free article: PMC5820781] [PubMed: 29386101]
    250.
    Bönisch C. et al. (2012) H2A.Z.2.2 is an alternatively spliced histone H2A.Z variant that causes severe nucleosome destabilization. Nucleic Acids Research 40: 5951–5964. [PMC free article: PMC3401452] [PubMed: 22467210]
    251.
    Giaimo B.D., Ferrante F., Herchenröther A., Hake S.B. and Borggrefe T. (2019) The histone variant H2A.Z in gene regulation. Epigenetics & Chromatin 12: 37. [PMC free article: PMC6570943] [PubMed: 31200754]
    252.
    Greenberg R.S., Long H.K., Swigut T. and Wysocka J. (2019) Single amino acid change underlies distinct roles of H2A.Z subtypes in human syndrome. Cell 178: 1421–1436. [PMC free article: PMC7103420] [PubMed: 31491386]
    253.
    Vardabasso C. et al. (2015) Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma. Molecular Cell 59: 75–88. [PMC free article: PMC4490946] [PubMed: 26051178]
    254.
    Paull T.T. et al. (2000) A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Current Biology 10: 886–895. [PubMed: 10959836]
    255.
    Scully R. and Xie A. (2013) Double strand break repair functions of histone H2AX. Mutation Research 750: 5–14. [PMC free article: PMC3818383] [PubMed: 23916969]
    256.
    Chakravarthy S. et al. (2005) Structural characterization of the histone variant macroH2A. Molecular and Cellular biology 25: 7616–7624. [PMC free article: PMC1190287] [PubMed: 16107708]
    257.
    Ladurner A.G. (2003) Inactivating chromosomes: A macro domain that minimizes transcription. Molecular Cell 12: 1–3. [PubMed: 12887886]
    258.
    Gaspar-Maia A. et al. (2013) MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency. Nature Communications 4: 1565. [PMC free article: PMC4055026] [PubMed: 23463008]
    259.
    Douet J. et al. (2017) MacroH2A histone variants maintain nuclear organization and heterochromatin architecture. Journal of Cell Science 130: 1570–1582. [PubMed: 28283545]
    260.
    Jiang X., Soboleva T.A. and Tremethick D.J. (2020) Short histone H2A variants: Small in stature but not in function. Cells 9: 867. [PMC free article: PMC7226823] [PubMed: 32252453]
    261.
    Soboleva T.A. et al. (2012) A unique H2A histone variant occupies the transcriptional start site of active genes. Nature Structural & Molecular Biology 19: 25–30. [PubMed: 22139013]
    262.
    Soboleva T.A. et al. (2017) A new link between transcriptional initiation and pre-mRNA splicing: The RNA binding histone variant H2A.B. PLOS Genetics 13: e1006633. [PMC free article: PMC5345878] [PubMed: 28234895]
    263.
    Anuar N.D. et al. (2019) Gene editing of the multi-copy H2A.B gene and its importance for fertility. Genome Biology 20: 23. [PMC free article: PMC6357441] [PubMed: 30704500]
    264.
    Molaro A. et al. (2020) Biparental contributions of the H2A.B histone variant control embryonic development in mice. PLOS Biology 18: e3001001. [PMC free article: PMC7757805] [PubMed: 33362208]
    265.
    Bao Y. et al. (2004) Nucleosomes containing the histone variant H2A.Bbd organize only 118 base pairs of DNA. EMBO Journal 23: 3314–3324. [PMC free article: PMC514500] [PubMed: 15257289]
    266.
    Hoghoughi N. et al. (2020) RNA-guided genomic localization of H2A.L.2 histone variant. Cells 9: 474. [PMC free article: PMC7072763] [PubMed: 32085641]
    267.
    Dahm R. (2010) From discovering to understanding. Friedrich Miescher’s attempts to uncover the function of DNA. EMBO Reports 11: 153–160. [PMC free article: PMC2838690] [PubMed: 20168329]
    268.
    Tagami H., Ray-Gallet D., Almouzni G. and Nakatani Y. (2004) Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116: 51–61. [PubMed: 14718166]
    269.
    Mito Y., Henikoff J.G. and Henikoff S. (2005) Genome-scale profiling of histone H3.3 replacement patterns. Nature Genetics 37: 1090–1097. [PubMed: 16155569]
    270.
    Elsaesser S.J., Goldberg A.D. and Allis C.D. (2010) New functions for an old variant: No substitute for histone H3.3. Current Opinion in Genetics & Development 20: 110–117. [PMC free article: PMC2860041] [PubMed: 20153629]
    271.
    Goldberg A.D. et al. (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140: 678–691. [PMC free article: PMC2885838] [PubMed: 20211137]
    272.
    Szenker E., Ray-Gallet D. and Almouzni G. (2011) The double face of the histone variant H3.3. Cell Research 21: 421–434. [PMC free article: PMC3193428] [PubMed: 21263457]
    273.
    van der Heijden G.W. et al. (2007) Chromosome-wide nucleosome replacement and H3.3 incorporation during mammalian meiotic sex chromosome inactivation. Nature Genetics 39: 251–258. [PubMed: 17237782]
    274.
    Ghanim G.E. et al. (2021) Structure of human telomerase holoenzyme with bound telomeric DNA. Nature 593: 449–453. [PMC free article: PMC7610991] [PubMed: 33883742]
    275.
    Hödl M. and Basler K. (2009) Transcription in the absence of histone H3.3. Current Biology 19: 1221–1226. [PubMed: 19523831]
    276.
    Cox S.G. et al. (2012) An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest. PLOS Genetics 8: e1002938. [PMC free article: PMC3447937] [PubMed: 23028350]
    277.
    Szenker E., Lacoste N. and Almouzni G. (2012) A developmental requirement for HIRA-dependent H3.3 deposition revealed at gastrulation in Xenopus. Cell Reports 1: 730–740. [PubMed: 22813747]
    278.
    Maze I. et al. (2015) Critical role of histone turnover in neuronal transcription and plasticity. Neuron 87: 77–94. [PMC free article: PMC4491146] [PubMed: 26139371]
    279.
    Bryant L. et al. (2020) Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients. Science Advances 6: eabc9207. [PMC free article: PMC7821880] [PubMed: 33268356]
    280.
    Schwartzentruber J. et al. (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482: 226–231. [PubMed: 22286061]
    281.
    Wu G. et al. (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nature Genetics 44: 251–253. [PMC free article: PMC3288377] [PubMed: 22286216]
    282.
    Muhire B.M., Booker M.A. and Tolstorukov M.Y. (2019) Non-neutral evolution of H3.3-encoding genes occurs without alterations in protein sequence. Scientific Reports 9: 8472. [PMC free article: PMC6560044] [PubMed: 31186448]
    283.
    Couldrey C., Carlton M.B.L., Nolan P.M., Colledge W.H. and Evans M.J. (1999) A retroviral gene trap insertion into the histone 3.3A gene causes partial neonatal lethality, stunted growth, neuromuscular deficits and male sub-fertility in transgenic mice. Human Molecular Genetics 8: 2489–2495. [PubMed: 10556297]
    284.
    Santenard A. et al. (2010) Heterochromatin formation in the mouse embryo requires critical residues of the histone variant H3.3. Nature Cell Biology 12: 853–862. [PMC free article: PMC3701880] [PubMed: 20676102]
    285.
    Jang C.-W., Shibata Y., Starmer J., Yee D. and Magnuson T. (2015) Histone H3.3 maintains genome integrity during mammalian development. Genes & Development 29: 1377–1392. [PMC free article: PMC4511213] [PubMed: 26159997]
    286.
    Sharma A.B., Dimitrov S., Hamiche A. and Van Dyck E. (2018) Centromeric and ectopic assembly of CENP-A chromatin in health and cancer: Old marks and new tracks. Nucleic Acids Research 47: 1051–1069. [PMC free article: PMC6379705] [PubMed: 30590707]
    287.
    McKinley K.L. and Cheeseman I.M. (2016) The molecular basis for centromere identity and function. Nature Reviews Molecular Cell Biology 17: 16–29. [PMC free article: PMC8603311] [PubMed: 26601620]
    288.
    Borg M. et al. (2020) Targeted reprogramming of H3K27me3 resets epigenetic memory in plant paternal chromatin. Nature Cell Biology 22: 621–629. [PMC free article: PMC7116658] [PubMed: 32393884]
    289.
    Hajkova P. et al. (2008) Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452: 877–881. [PMC free article: PMC3847605] [PubMed: 18354397]
    290.
    Grosschedl R., Giese K. and Pagel J. (1994) HMG domain proteins: Architectural elements in the assembly of nucleoprotein structures. Trends in Genetics 10: 94–100. [PubMed: 8178371]
    291.
    Bianchi M.E. and Agresti A. (2005) HMG proteins: Dynamic players in gene regulation and differentiation. Current Opinion in Genetics and Development 15: 496–506. [PubMed: 16102963]
    292.
    Mallik R., Kundu A. and Chaudhuri S. (2018) High mobility group proteins: The multifaceted regulators of chromatin dynamics. Nucleus 61: 213–226.
    293.
    Dodonova S.O., Zhu F., Dienemann C., Taipale J. and Cramer P. (2020) Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function. Nature 580: 669–672. [PubMed: 32350470]
    294.
    Friedman J.R. and Kaestner K.H. (2006) The Foxa family of transcription factors in development and metabolism. Cellular and Molecular Life Sciences 63: 2317–2328. [PubMed: 16909212]
    295.
    Sekiya T., Muthurajan U.M., Luger K., Tulin A.V. and Zaret K.S. (2009) Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA. Genes & Development 23: 804–809. [PMC free article: PMC2666343] [PubMed: 19339686]
    296.
    Zaret K.S. and Carroll J.S. (2011) Pioneer transcription factors: Establishing competence for gene expression. Genes & Development 25: 2227–2241. [PMC free article: PMC3219227] [PubMed: 22056668]
    297.
    Fournier M. et al. (2016) FOXA and master transcription factors recruit Mediator and Cohesin to the core transcriptional regulatory circuitry of cancer cells. Scientific Reports 6: 34962. [PMC free article: PMC5064413] [PubMed: 27739523]
    298.
    Iwafuchi-Doi M. et al. (2016) The pioneer transcription factor FoxA maintains an accessible nucleosome configuration at enhancers for tissue-specific gene activation. Molecular Cell 62: 79–91. [PMC free article: PMC4826471] [PubMed: 27058788]
    299.
    Gurard-Levin Z.A., Quivy J.-P. and Almouzni G. (2014) Histone chaperones: Assisting histone traffic and nucleosome dynamics. Annual Review of Biochemistry 83: 487–517. [PubMed: 24905786]
    300.
    Hammond C.M., Strømme C.B., Huang H., Patel D.J. and Groth A. (2017) Histone chaperone networks shaping chromatin function. Nature Reviews Molecular Cell Biology 18: 141–158. [PMC free article: PMC5319910] [PubMed: 28053344]
    301.
    Clapier C.R., Iwasa J., Cairns B.R. and Peterson C.L. (2017) Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nature Reviews Molecular Cell Biology 18: 407–422. [PMC free article: PMC8127953] [PubMed: 28512350]
    302.
    Grunstein M. (1990) Nucleosomes: Regulators of transcription. Trends in Genetics 6: 395–400. [PubMed: 2087781]
    303.
    Lee D.Y., Hayes J.J., Pruss D. and Wolffe A.P. (1993) A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72: 73–84. [PubMed: 8422685]
    304.
    Guarente L. (1995) Transcriptional coactivators in yeast and beyond. Trends in Biochemical Sciences 20: 517–521. [PubMed: 8571454]
    305.
    Durrin L.K., Mann R.K., Kayne P.S. and Grunstein M. (1991) Yeast histone H4 N-terminal sequence is required for promoter activation in vivo. Cell 65: 1023–1031. [PubMed: 2044150]
    306.
    Brownell J.E. et al. (1996) Tetrahymena histone acetyltransferase A: A homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84: 843–851. [PubMed: 8601308]
    307.
    Candau R., Zhou J.X., Allis C.D. and Berger S.L. (1997) Histone acetyltransferase activity and interaction with ADA2 are critical for GCN5 function in vivo. EMBO Journal 16: 555–565. [PMC free article: PMC1169659] [PubMed: 9034338]
    308.
    Taunton J., Hassig C.A. and Schreiber S.L. (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272: 408–411. [PubMed: 8602529]
    309.
    Bannister A.J. and Kouzarides T. (1996) The CBP co-activator is a histone acetyltransferase. Nature 384: 641–643. [PubMed: 8967953]
    310.
    Grant P.A. et al. (1997) Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: Characterization of an Ada complex and the SAGA (Spt/Ada) complex. Genes & Development 11: 1640–1650. [PubMed: 9224714]
    311.
    Tan M. et al. (2011) Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146: 1016–1028. [PMC free article: PMC3176443] [PubMed: 21925322]
    312.
    Arnaudo A.M. and Garcia B.A. (2013) Proteomic characterization of novel histone post-translational modifications. Epigenetics & Chromatin 6: 24. [PMC free article: PMC3737111] [PubMed: 23916056]
    313.
    Peng Z., Mizianty M.J., Xue B., Kurgan L. and Uversky V.N. (2012) More than just tails: Intrinsic disorder in histone proteins. Molecular BioSystems 8: 1886–1901. [PubMed: 22543956]
    314.
    Watson M. and Stott K. (2019) Disordered domains in chromatin-binding proteins. Essays in Biochemistry 63: 147–156. [PubMed: 30940742]
    315.
    Cuthbert G.L. et al. (2004) Histone deimination antagonizes arginine methylation. Cell 118: 545–553. [PubMed: 15339660]
    316.
    Christophorou M.A. et al. (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature 507: 104–108. [PMC free article: PMC4843970] [PubMed: 24463520]
    317.
    Li P. et al. (2010) PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. Journal of Experimental Medicine 207: 1853–1862. [PMC free article: PMC2931169] [PubMed: 20733033]
    318.
    Brinkmann V. and Zychlinsky A. (2012) Neutrophil extracellular traps: Is immunity the second function of chromatin? Journal of Cell Biology 198: 773–783. [PMC free article: PMC3432757] [PubMed: 22945932]
    319.
    Apel F. et al. (2021) The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps. Science Signaling 14: eaax7942. [PubMed: 33688080]
    320.
    Kouzarides T. (2007) Chromatin modifications and their function. Cell 128: 693–705. [PubMed: 17320507]
    321.
    Suganuma T. and Workman J.L. (2011) Signals and combinatorial functions of histone modifications. Annual Review of Biochemistry 80: 473–499. [PubMed: 21529160]
    322.
    Wang Y. et al. (2009) Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. Journal of Cell Biology 184: 205–213. [PMC free article: PMC2654299] [PubMed: 19153223]
    323.
    Kebede A.F. et al. (2017) Histone propionylation is a mark of active chromatin. Nature Structural & Molecular Biology 24: 1048–1056. [PubMed: 29058708]
    324.
    Wan J., Liu H., Chu J. and Zhang H. (2019) Functions and mechanisms of lysine crotonylation. Journal of Cellular and Molecular Medicine 23: 7163–7169. [PMC free article: PMC6815811] [PubMed: 31475443]
    325.
    Qin B. et al. (2019) UFL1 promotes histone H4 ufmylation and ATM activation. Nature Communications 10: 1242. [PMC free article: PMC6423285] [PubMed: 30886146]
    326.
    Qin B. et al. (2020) STK38 promotes ATM activation by acting as a reader of histone H4 ufmylation. Science Advances 6: eaax8214. [PMC free article: PMC7269669] [PubMed: 32537488]
    327.
    Zhang D. et al. (2019) Metabolic regulation of gene expression by histone lactylation. Nature 574: 575–580. [PMC free article: PMC6818755] [PubMed: 31645732]
    328.
    Lepack A.E. et al. (2020) Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking. Science 368: 197–201. [PMC free article: PMC7228137] [PubMed: 32273471]
    329.
    Farrelly L.A. et al. (2019) Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3. Nature 567: 535–539. [PMC free article: PMC6557285] [PubMed: 30867594]
    330.
    Mews P. et al. (2019) Alcohol metabolism contributes to brain histone acetylation. Nature 574: 717–721. [PMC free article: PMC6907081] [PubMed: 31645761]
    331.
    Renthal W. and Nestler E.J. (2009) Histone acetylation in drug addiction. Seminars in Cell & Developmental Biology 20: 387–394. [PMC free article: PMC2704458] [PubMed: 19560043]
    332.
    Hyun K., Jeon J., Park K. and Kim J. (2017) Writing, erasing and reading histone lysine methylations. Experimental & Molecular Medicine 49: e324. [PMC free article: PMC6130214] [PubMed: 28450737]
    333.
    Lavarone E., Barbieri C.M. and Pasini D. (2019) Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity. Nature Communications 10: 1679. [PMC free article: PMC6459869] [PubMed: 30976011]
    334.
    Cooper S. et al. (2014) Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment. Cell Reports 7: 1456–1470. [PMC free article: PMC4062935] [PubMed: 24857660]
    335.
    Cao Q. et al. (2014) The central role of EED in the orchestration of polycomb group complexes. Nature Communications 5: 3127. [PMC free article: PMC4073494] [PubMed: 24457600]
    336.
    van der Vlag J. and Otte A.P. (1999) Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nature Genetics 23: 474–478. [PubMed: 10581039]
    337.
    Herz H.-M., Garruss A. and Shilatifard A. (2013) SET for life: Biochemical activities and biological functions of SET domain-containing proteins. Trends in Biochemical Sciences 38: 621–639. [PMC free article: PMC3941473] [PubMed: 24148750]
    338.
    Ma R.-G., Zhang Y., Sun T.-T. and Cheng B. (2014) Epigenetic regulation by polycomb group complexes: Docus on roles of CBX proteins. Journal of Zhejiang University. Science B 15: 412–428. [PMC free article: PMC4076598] [PubMed: 24793759]
    339.
    Gil J. and O’Loghlen A. (2014) PRC1 complex diversity: Where is it taking us? Trends in Cell Biology 24: 632–641. [PubMed: 25065329]
    340.
    Chittock E.C., Latwiel S., Miller T.C.R. and Müller C.W. (2017) Molecular architecture of polycomb repressive complexes. Biochemical Society Transactions 45: 193–205. [PMC free article: PMC5310723] [PubMed: 28202673]
    341.
    Ren X. and Kerppola T.K. (2011) REST interacts with Cbx proteins and regulates polycomb repressive complex 1 occupancy at RE1 elements. Molecular and Cellular Biology 31: 2100–2110. [PMC free article: PMC3133345] [PubMed: 21402785]
    342.
    Plys A.J. et al. (2019) Phase separation of Polycomb-repressive complex 1 is governed by a charged disordered region of CBX2. Genes & Development 33: 1–15. [PMC free article: PMC6601514] [PubMed: 31171700]
    343.
    Conaway R.C. and Conaway J.W. (2011) Origins and activity of the mediator complex. Seminars in Cell & Developmental Biology 22: 729–734. [PMC free article: PMC3207015] [PubMed: 21821140]
    344.
    Heger P., Marin B., Bartkuhn M., Schierenberg E. and Wiehe T. (2012) The chromatin insulator CTCF and the emergence of metazoan diversity. Proceedings of the National Academy of Sciences USA 109: 17507–17512. [PMC free article: PMC3491479] [PubMed: 23045651]
    345.
    Tchasovnikarova I.A. et al. (2015) Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science 348: 1481–1485. [PMC free article: PMC4487827] [PubMed: 26022416]
    346.
    Emerson R.O. and Thomas J.H. (2009) Adaptive evolution in zinc finger transcription factors. PLOS Genetics 5: e1000325. [PMC free article: PMC2604467] [PubMed: 19119423]
    347.
    Turelli P. et al. (2020) Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons. Science Advances 6: eaba3200. [PMC free article: PMC7455193] [PubMed: 32923624]
    348.
    Bannister A.J. et al. (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410: 120–124. [PubMed: 11242054]
    349.
    Ruthenburg A.J., Allis C.D. and Wysocka J. (2007) Methylation of lysine 4 on histone H3: Intricacy of writing and reading a single epigenetic mark. Molecular Cell 25: 15–30. [PubMed: 17218268]
    350.
    Bonasio R., Lecona E. and Reinberg D. (2010) MBT domain proteins in development and disease. Seminars in Cell & Developmental Biology 21: 221–230. [PMC free article: PMC3772645] [PubMed: 19778625]
    351.
    Yun M., Wu J., Workman J.L. and Li B. (2011) Readers of histone modifications. Cell Research 21: 564–578. [PMC free article: PMC3131977] [PubMed: 21423274]
    352.
    Sanchez R. and Zhou M.-M. (2011) The PHD finger: A versatile epigenome reader. Trends in Biochemical Sciences 36: 364–372. [PMC free article: PMC3130114] [PubMed: 21514168]
    353.
    Liu W. et al. (2013) Brd4 and JMJD6-associated anti-pause enhancers in regulation of transcriptional pause release. Cell 155: 1581–1595. [PMC free article: PMC3886918] [PubMed: 24360279]
    354.
    Shelton S.B. et al. (2018) Crosstalk between the RNA methylation and histone-binding activities of MePCE regulates P-TEFb activation on chromatin. Cell Reports 22: 1374–1383. [PubMed: 29425494]
    355.
    Mita M.M. and Mita A.C. (2020) Bromodomain inhibitors a decade later: A promise unfulfilled? British Journal of Cancer 123: 1713–1714. [PMC free article: PMC7722711] [PubMed: 32989227]
    356.
    Kouzarides T. (2000) Acetylation: A regulatory modification to rival phosphorylation? EMBO Journal 19: 1176–1179. [PMC free article: PMC305658] [PubMed: 10716917]
    357.
    Zucconi B.E. et al. (2019) Combination targeting of the bromodomain and acetyltransferase active site of p300/CBP. Biochemistry 58: 2133–2143. [PMC free article: PMC6948846] [PubMed: 30924641]
    358.
    Maurer-Stroh S. et al. (2003) The Tudor domain ‘Royal Family’: Tudor, plant Agenet, chromo, PWWP and MBT domains. Trends in Biochemical Sciences 28: 69–74. [PubMed: 12575993]
    359.
    Hard R. et al. (2018) Deciphering and engineering chromodomain-methyllysine peptide recognition. Science Advances 4: eaau1447. [PMC free article: PMC6221542] [PubMed: 30417094]
    360.
    Chi P., Allis C.D. and Wang G.G. (2010) Covalent histone modifications - miswritten, misinterpreted and mis-erased in human cancers. Nature Reviews Cancer 10: 457–469. [PMC free article: PMC3262678] [PubMed: 20574448]
    361.
    Audia J.E. and Campbell R.M. (2016) Histone modifications and cancer. Cold Spring Harbor Perspectives in Biology 8: a019521. [PMC free article: PMC4817802] [PubMed: 27037415]
    362.
    Reddy T.E. (2017) The functional genome: Epigenetics and epigenomics, in G. S. Ginsburg, H. F. Willard, J. Strickler and M. Stuart McKinney (eds.) Genomic and Precision Medicine (3rd edition) (Academic Press, New York).
    363.
    Nacev B.A. et al. (2019) The expanding landscape of ‘oncohistone’ mutations in human cancers. Nature 567: 473–478. [PMC free article: PMC6512987] [PubMed: 30894748]
    364.
    Zhao Z. and Shilatifard A. (2019) Epigenetic modifications of histones in cancer. Genome Biology 20: 245. [PMC free article: PMC6868810] [PubMed: 31747960]
    365.
    Winters A.C. and Bernt K.M. (2017) MLL-rearranged leukemias - an update on science and clinical approaches. Frontiers in Pediatrics 5: 4. [PMC free article: PMC5299633] [PubMed: 28232907]
    366.
    Wang G.G. et al. (2009) Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature 459: 847–851. [PMC free article: PMC2697266] [PubMed: 19430464]
    367.
    Williams S.R. et al. (2010) Haploinsufficiency of HDAC4 causes Brachydactyly Mental Retardation Syndrome, with Brachydactyly Type E, developmental delays, and behavioral problems. American Journal of Human Genetics 87: 219–228. [PMC free article: PMC2917703] [PubMed: 20691407]
    368.
    Park S.-Y. and Kim J.-S. (2020) A short guide to histone deacetylases including recent progress on class II enzymes. Experimental & Molecular Medicine 52: 204–212. [PMC free article: PMC7062823] [PubMed: 32071378]
    369.
    Abascal F. et al. (2020) Perspectives on ENCODE. Nature 583: 693–698. [PMC free article: PMC7410827] [PubMed: 32728248]
    370.
    Strahl B.D. and Allis C.D. (2000) The language of covalent histone modifications. Nature 403: 41–45. [PubMed: 10638745]
    371.
    Allis C.D. (2015) “Modifying” my career toward chromatin biology. Journal of Biological Chemistry 290: 15904–15908. [PMC free article: PMC4481195] [PubMed: 25944906]
    372.
    Ptashne M. (1967) Isolation of the lambda phage repressor. Proceedings of the National Academy of Sciences USA 57: 306–313. [PMC free article: PMC335506] [PubMed: 16591470]
    373.
    Ptashne M. (1967) Specific binding of the lambda phage repressor to lambda DNA. Nature 214: 232–234. [PubMed: 6034235]
    374.
    Brent R. and Ptashne M. (1985) A eukaryotic transcriptional activator bearing the DNA specificity of a prokaryotic repressor. Cell 43: 729–736. [PubMed: 3907859]
    375.
    Ptashne M. (2013) Epigenetics: Core misconcept. Proceedings of the National Academy of Sciences USA 110: 7101–7103. [PMC free article: PMC3645541] [PubMed: 23584020]
    376.
    Saha S., Ansari A.Z., Jarrell K.A. and Ptashne M. (2003) RNA sequences that work as transcriptional activating regions. Nucleic Acids Research 31: 1565–1570. [PMC free article: PMC149820] [PubMed: 12595565]
    377.
    Goldberg A.D., Allis C.D. and Bernstein E. (2007) Epigenetics: A landscape takes shape. Cell 128: 635–638. [PubMed: 17320500]
    378.
    Allis C.D. et al. (2007) New nomenclature for chromatin-modifying enzymes. Cell 131: 633–636. [PubMed: 18022353]
    379.
    Turner B.M. (1993) Decoding the nucleosome. Cell 75: 5–8. [PubMed: 8402900]
    380.
    Allis C.D., Caparros M.-L., Jenuwein T. and Reinberg D. (2015) Epigenetics (Cold Spring Harbor Laboratory Press, New York).
    381.
    Allis C.D. and Jenuwein T. (2016) The molecular hallmarks of epigenetic control. Nature Reviews Genetics 17: 487–500. [PubMed: 27346641]
    382.
    Barski A. et al. (2007) High-resolution profiling of histone methylations in the human genome. Cell 129: 823–837. [PubMed: 17512414]
    383.
    The ENCODE Consortium (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447: 799–816. [PMC free article: PMC2212820] [PubMed: 17571346]
    384.
    Wang Z. et al. (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nature Genetics 40: 897–903. [PMC free article: PMC2769248] [PubMed: 18552846]
    385.
    The Encode Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74. [PMC free article: PMC3439153] [PubMed: 22955616]
    386.
    Kundaje A. et al. (2015) Integrative analysis of 111 reference human epigenomes. Nature 518: 317–330. [PMC free article: PMC4530010] [PubMed: 25693563]
    387.
    Gardner K.E., Allis C.D. and Strahl B.D. (2011) OPERating ON chromatin, a colorful language where context matters. Journal of Molecular Biology 409: 36–46. [PMC free article: PMC3085666] [PubMed: 21272588]
    388.
    Henikoff S. and Shilatifard A. (2011) Histone modification: Cause or cog? Trends in Genetics 27: 389–396. [PubMed: 21764166]
    389.
    Valencia-Sánchez M.I. et al. (2021) Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation. Science 371: eabc6663. [PMC free article: PMC8279004] [PubMed: 33479126]
    390.
    Pokholok D.K. et al. (2005) Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122: 517–527. [PubMed: 16122420]
    391.
    Basilicata M.F. et al. (2018) De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation. Nature Genetics 50: 1442–1451. [PMC free article: PMC7398719] [PubMed: 30224647]
    392.
    Monserrat J. et al. (2021) Disruption of the MSL complex inhibits tumour maintenance by exacerbating chromosomal instability. Nature Cell Biology 23: 401–412. [PMC free article: PMC7610593] [PubMed: 33837287]
    393.
    Motazedian A. and Dawson M.A. (2021) MSL pushes genomic instability over the edge. Nature Cell Biology 23: 295–296. [PubMed: 33837286]
    394.
    Radzisheuskaya A. et al. (2021) Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis. Molecular Cell 81: 1749–1765. [PMC free article: PMC8056186] [PubMed: 33657400]
    395.
    Creyghton M.P. et al. (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proceedings of the National Academy of Sciences USA 107: 21931–21936. [PMC free article: PMC3003124] [PubMed: 21106759]
    396.
    Zhang T., Zhang Z., Dong Q., Xiong J. and Zhu B. (2020) Histone H3K27 acetylation is dispensable for enhancer activity in mouse embryonic stem cells. Genome Biology 21: 45. [PMC free article: PMC7035716] [PubMed: 32085783]
    397.
    Trojer P. and Reinberg D. (2007) Facultative heterochromatin: Is there a distinctive molecular signature? Molecular Cell 28: 1–13. [PubMed: 17936700]
    398.
    Khan A.A., Lee A.J. and Roh T.-Y. (2015) Polycomb group protein-mediated histone modifications during cell differentiation. Epigenomics 7: 75–84. [PubMed: 25687468]
    399.
    Gibson W.T. et al. (2012) Mutations in EZH2 cause weaver syndrome. American Journal of Human Genetics 90: 110–118. [PMC free article: PMC3257956] [PubMed: 22177091]
    400.
    Zenk F. et al. (2017) Germ line–inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition. Science 357: 212–216. [PubMed: 28706074]
    401.
    Guo Y., Zhao S. and Wang G.G. (2021) Polycomb gene silencing mechanisms: PRC2 chromatin targeting, H3K27me3 ‘readout’, and phase separation-based compaction. Trends in Genetics 37: 547–565. [PMC free article: PMC8119337] [PubMed: 33494958]
    402.
    Cai Y. et al. (2021) H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions. Nature Communications 12: 719. [PMC free article: PMC7846766] [PubMed: 33514712]
    403.
    Ahmad K. and Henikoff S. (2021) The H3.3K27M oncohistone antagonizes reprogramming in Drosophila. PLOS Genetics 17: e1009225. [PMC free article: PMC8320987] [PubMed: 34280185]
    404.
    Pengelly A.R., Copur Ö., Jäckle H., Herzig A. and Müller J. (2013) A histone mutant reproduces the phenotype caused by loss of histone-modifying factor Polycomb. Science 339: 698–699. [PubMed: 23393264]
    405.
    Pease N.A. et al. (2021) Tunable, division-independent control of gene activation timing by a polycomb switch. Cell Reports 34: 108888. [PMC free article: PMC8024876] [PubMed: 33761349]
    406.
    Heurteau A. et al. (2020) Insulator-based loops mediate the spreading of H3K27me3 over distant micro-domains repressing euchromatin genes. Genome Biology 21: 193. [PMC free article: PMC7397589] [PubMed: 32746892]
    407.
    Kwasnieski J.C., Fiore C., Chaudhari H.G. and Cohen B.A. (2014) High-throughput functional testing of ENCODE segmentation predictions. Genome Research 24: 1595–1602. [PMC free article: PMC4199366] [PubMed: 25035418]
    408.
    Bonn S. et al. (2012) Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development. Nature Genetics 44: 148–156. [PubMed: 22231485]
    409.
    Taylor G.C.A., Eskeland R., Hekimoglu-Balkan B., Pradeepa M.M. and Bickmore W.A. (2013) H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction. Genome Research 23: 2053–2065. [PMC free article: PMC3847775] [PubMed: 23990607]
    410.
    Osmala M. and Lähdesmäki H. (2020) Enhancer prediction in the human genome by probabilistic modelling of the chromatin feature patterns. BMC Bioinformatics 21: 317. [PMC free article: PMC7370432] [PubMed: 32689977]
    411.
    Santos-Rosa H. et al. (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419: 407–411. [PubMed: 12353038]
    412.
    Adelman K. and Lis J.T. (2012) Promoter-proximal pausing of RNA polymerase II: Emerging roles in metazoans. Nature Reviews Genetics 13: 720–731. [PMC free article: PMC3552498] [PubMed: 22986266]
    413.
    Jonkers I. and Lis J.T. (2015) Getting up to speed with transcription elongation by RNA polymerase II. Nature Reviews Molecular Cell Biology 16: 167–177. [PMC free article: PMC4782187] [PubMed: 25693130]
    414.
    Saldi T., Riemondy K., Erickson B. and Bentley D.L. (2021) Alternative RNA structures formed during transcription depend on elongation rate and modify RNA processing. Molecular Cell 81: 1789–1801. [PMC free article: PMC8052309] [PubMed: 33631106]
    415.
    Schneider R. et al. (2004) Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nature Cell Biology 6: 73–77. [PubMed: 14661024]
    416.
    Guenther M.G., Levine S.S., Boyer L.A., Jaenisch R. and Young R.A. (2007) A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130: 77–88. [PMC free article: PMC3200295] [PubMed: 17632057]
    417.
    Mikkelsen T.S. et al. (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448: 553–560. [PMC free article: PMC2921165] [PubMed: 17603471]
    418.
    Vermeulen M. et al. (2007) Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131: 58–69. [PubMed: 17884155]
    419.
    Lauberth S.M. et al. (2013) H3K4me3 interactions with TAF3 regulate preinitiation complex assembly and selective gene activation. Cell 152: 1021–1036. [PMC free article: PMC3588593] [PubMed: 23452851]
    420.
    Howe F.S., Fischl H., Murray S.C. and Mellor J. (2017) Is H3K4me3 instructive for transcription activation? BioEssays 39: e201600095. [PubMed: 28004446]
    421.
    Mercer T.R. et al. (2011) Expression of distinct RNAs from 3′ untranslated regions. Nucleic Acids Research 39: 2393–2403. [PMC free article: PMC3064787] [PubMed: 21075793]
    422.
    Bernstein B.E. et al. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125: 315–326. [PubMed: 16630819]
    423.
    Vastenhouw N.L. et al. (2010) Chromatin signature of embryonic pluripotency is established during genome activation. Nature 464: 922–926. [PMC free article: PMC2874748] [PubMed: 20336069]
    424.
    Chovanec P. et al. (2021) Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states. Nature Communications 12: 2098. [PMC free article: PMC8026613] [PubMed: 33828098]
    425.
    Mei H. et al. (2021) H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos. Nature Genetics 53: 539–550. [PubMed: 33821003]
    426.
    Chen Z., Djekidel M.N. and Zhang Y. (2021) Distinct dynamics and functions of H2AK119ub1 and H3K27me3 in mouse preimplantation embryos. Nature Genetics 53: 551–563. [PMC free article: PMC8092361] [PubMed: 33821005]
    427.
    Armache A. et al. (2020) Histone H3.3 phosphorylation amplifies stimulation-induced transcription. Nature 583: 852–857. [PMC free article: PMC7517595] [PubMed: 32699416]
    428.
    Lachner M., O‘Carroll D., Rea S., Mechtler K. and Jenuwein T. (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410: 116–120. [PubMed: 11242053]
    429.
    Cubeñas-Potts C. and Matunis M.J. (2013) SUMO: A multifaceted modifier of chromatin structure and function. Developmental Cell 24: 1–12. [PMC free article: PMC3555686] [PubMed: 23328396]
    430.
    Kolasinska-Zwierz P. et al. (2009) Differential chromatin marking of introns and expressed exons by H3K36me3. Nature Genetics 41: 376–381. [PMC free article: PMC2648722] [PubMed: 19182803]
    431.
    Leung C.S. et al. (2019) H3K36 methylation and the chromodomain protein Eaf3 are required for proper cotranscriptional spliceosome assembly. Cell Reports 27: 3760–3769. [PMC free article: PMC6904931] [PubMed: 31242410]
    432.
    Hilton I.B. et al. (2015) Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nature Biotechnology 33: 510–517. [PMC free article: PMC4430400] [PubMed: 25849900]
    433.
    Kearns N.A. et al. (2015) Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nature Methods 12: 401–403. [PMC free article: PMC4414811] [PubMed: 25775043]
    434.
    Cano-Rodriguez D. et al. (2016) Writing of H3K4Me3 overcomes epigenetic silencing in a sustained but context-dependent manner. Nature Communications 7: 12284. [PMC free article: PMC4987519] [PubMed: 27506838]
    435.
    Labrie V. et al. (2016) Lactase nonpersistence is directed by DNA-variation-dependent epigenetic aging. Nature Structural & Molecular Biology 23: 566–573. [PMC free article: PMC4899171] [PubMed: 27159559]
    436.
    Chen L.-F. et al. (2019) Enhancer histone acetylation modulates transcriptional bursting dynamics of neuronal activity-inducible genes. Cell Reports 26: 1174–1188. [PMC free article: PMC6376993] [PubMed: 30699347]
    437.
    Li J. et al. (2021) Programmable human histone phosphorylation and gene activation using a CRISPR/Cas9-based chromatin kinase. Nature Communications 12: 896. [PMC free article: PMC7873277] [PubMed: 33563994]
    438.
    Liscovitch-Brauer N. et al. (2021) Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens. Nature Biotechnology 39: 1270–1277. [PMC free article: PMC8516442] [PubMed: 33927415]
    439.
    Cheung P. et al. (2018) Single-cell chromatin modification profiling reveals increased epigenetic variations with aging. Cell 173: 1385–1397. [PMC free article: PMC5984186] [PubMed: 29706550]
    440.
    Schwartz S., Meshorer E. and Ast G. (2009) Chromatin organization marks exon-intron structure. Nature Structural & Molecular Biology 16: 990–995. [PubMed: 19684600]
    441.
    Tilgner H. et al. (2009) Nucleosome positioning as a determinant of exon recognition. Nature Structural & Molecular Biology 16: 996–1001. [PubMed: 19684599]
    442.
    Andersson R., Enroth S., Rada-Iglesias A., Wadelius C. and Komorowski J. (2009) Nucleosomes are well positioned in exons and carry characteristic histone modifications. Genome Research 19: 1732–1741. [PMC free article: PMC2765275] [PubMed: 19687145]
    443.
    Nahkuri S., Taft R.J. and Mattick J.S. (2009) Nucleosomes are preferentially positioned at exons in somatic and sperm cells. Cell Cycle 8: 3420–3424. [PubMed: 19823040]
    444.
    Naftelberg S., Schor I.E., Ast G. and Kornblihtt A.R. (2015) Regulation of alternative splicing through coupling with transcription and chromatin structure. Annual Review of Biochemistry 84: 165–198. [PubMed: 26034889]
    445.
    Mercer T.R. et al. (2013) DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements. Nature Genetics 45: 852–859. [PMC free article: PMC4405174] [PubMed: 23793028]
    446.
    Schor I.E., Rascovan N., Pelisch F., Alló M. and Kornblihtt A.R. (2009) Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proceedings of the National Academy of Sciences USA 106: 4325–4330. [PMC free article: PMC2657401] [PubMed: 19251664]
    447.
    Luco R.F. et al. (2010) Regulation of alternative splicing by histone modifications. Science 327: 996–1000. [PMC free article: PMC2913848] [PubMed: 20133523]
    448.
    Luco R.F. and Misteli T. (2011) More than a splicing code: Integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation. Current Opinion in Genetics and Development 21: 366–372. [PMC free article: PMC6317717] [PubMed: 21497503]
    449.
    Schor I.E., Fiszbein A., Petrillo E. and Kornblihtt A.R. (2013) Intragenic epigenetic changes modulate NCAM alternative splicing in neuronal differentiation. EMBO Journal 32: 2264–2274. [PMC free article: PMC3746202] [PubMed: 23892457]
    450.
    Xu Y., Zhao W., Olson S.D., Prabhakara K.S. and Zhou X. (2018) Alternative splicing links histone modifications to stem cell fate decision. Genome Biology 19: 133. [PMC free article: PMC6138936] [PubMed: 30217220]
    451.
    Rahhal R. and Seto E. (2019) Emerging roles of histone modifications and HDACs in RNA splicing. Nucleic Acids Research 47: 4911–4926. [PMC free article: PMC6547430] [PubMed: 31162605]
    452.
    Hu Q., Greene C.S. and Heller E.A. (2020) Specific histone modifications associate with alternative exon selection during mammalian development. Nucleic Acids Research 48: 4709–4724. [PMC free article: PMC7229819] [PubMed: 32319526]
    453.
    Agirre E., Oldfield A.J., Bellora N., Segelle A. and Luco R.F. (2021) Splicing-associated chromatin signatures: A combinatorial and position-dependent role for histone marks in splicing definition. Nature Communications 12: 682. [PMC free article: PMC7846797] [PubMed: 33514745]
    454.
    Alló M. et al. (2009) Control of alternative splicing through siRNA-mediated transcriptional gene silencing. Nature Structural & Molecular Biology 16: 717–724. [PubMed: 19543290]
    455.
    Guang S. et al. (2010) Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription. Nature 465: 1097–1101. [PMC free article: PMC2892551] [PubMed: 20543824]
    456.
    Taft R.J. et al. (2010) Nuclear-localized tiny RNAs are associated with transcription initiation and splice sites in metazoans. Nature Structural & Molecular Biology 17: 1030–1034. [PubMed: 20622877]
    457.
    Fan J., Krautkramer K.A., Feldman J.L. and Denu J.M. (2015) Metabolic regulation of histone post-translational modifications. ACS Chemical Biology 10: 95–108. [PMC free article: PMC4407823] [PubMed: 25562692]
    458.
    Berger S.L. and Sassone-Corsi P. (2016) Metabolic signaling to chromatin. Cold Spring Harbor Perspectives in Biology 8: a019463. [PMC free article: PMC5088527] [PubMed: 26492570]
    459.
    Etchegaray J.-P. and Mostoslavsky R. (2016) Interplay between metabolism and epigenetics: A nuclear adaptation to environmental changes. Molecular Cell 62: 695–711. [PMC free article: PMC4893201] [PubMed: 27259202]
    460.
    Costello K.R. and Schones D.E. (2018) Chromatin modifications in metabolic disease: Potential mediators of long-term disease risk. WIREs Systems Biology and Medicine 10: e1416. [PMC free article: PMC6002879] [PubMed: 29369528]
    461.
    Musselman C.A. and Kutateladze T.G. (2021) Characterization of functional disordered regions within chromatin-associated proteins. iScience 24: 102070. [PMC free article: PMC7873657] [PubMed: 33604523]
    462.
    Hatos A. et al. (2020) DisProt: Intrinsic protein disorder annotation in 2020. Nucleic Acids Research 48: D269–76. [PMC free article: PMC7145575] [PubMed: 31713636]
    463.
    Samata M. et al. (2020) Intergenerationally maintained histone H4 lysine 16 acetylation is instructive for future gene activation. Cell 182: 127–144. [PubMed: 32502394]
    464.
    Richard Albert J. and Greenberg M.V.C. (2021) The Polycomb landscape in mouse development. Nature Genetics 53: 427–429. [PubMed: 33821004]
    465.
    Kang H. et al. (2020) Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation. Genes & Development 34: 913–930. [PMC free article: PMC7328517] [PubMed: 32499403]
    466.
    Pelham-Webb B. et al. (2021) H3K27ac bookmarking promotes rapid post-mitotic activation of the pluripotent stem cell program without impacting 3D chromatin reorganization. Molecular Cell 81: 1732–1748. [PMC free article: PMC8052294] [PubMed: 33730542]
    467.
    Escobar T.M. et al. (2019) Active and repressed chromatin domains exhibit distinct nucleosome segregation during DNA replication. Cell 179: 953–963. [PMC free article: PMC6917041] [PubMed: 31675501]
    468.
    Stewart-Morgan K.R., Petryk N. and Groth A. (2020) Chromatin replication and epigenetic cell memory. Nature Cell Biology 22: 361–371. [PubMed: 32231312]
    469.
    Escobar T.M., Loyola A. and Reinberg D. (2021) Parental nucleosome segregation and the inheritance of cellular identity. Nature Reviews Genetics 22: 379–392. [PMC free article: PMC8609916] [PubMed: 33500558]
    470.
    Klein K.N. et al. (2021) Replication timing maintains the global epigenetic state in human cells. Science 372: 371–378. [PMC free article: PMC8173839] [PubMed: 33888635]
    471.
    Saxton D.S. and Rine J. (2019) Epigenetic memory independent of symmetric histone inheritance. eLife 8: e51421. [PMC free article: PMC6850775] [PubMed: 31613222]
    472.
    Francis N.J., Follmer N.E., Simon M.D., Aghia G. and Butler J.D. (2009) Polycomb proteins remain bound to chromatin and DNA during DNA replication in vitro. Cell 137: 110–122. [PMC free article: PMC2667909] [PubMed: 19303136]
    473.
    Budhavarapu V.N., Chavez M. and Tyler J.K. (2013) How is epigenetic information maintained through DNA replication? Epigenetics & Chromatin 6: 32. [PMC free article: PMC3852060] [PubMed: 24225278]
    474.
    Métivier R. et al. (2003) Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115: 751–763. [PubMed: 14675539]
    475.
    Métivier R., Reid G. and Gannon F. (2006) Transcription in four dimensions: Nuclear receptor-directed initiation of gene expression. EMBO Reports 7: 161–167. [PMC free article: PMC1369254] [PubMed: 16452926]
    476.
    Margueron R. and Reinberg D. (2010) Chromatin structure and the inheritance of epigenetic information. Nature Reviews Genetics 11: 285–296. [PMC free article: PMC3760772] [PubMed: 20300089]
    477.
    Moazed D. (2011) Mechanisms for the inheritance of chromatin states. Cell 146: 510–518. [PMC free article: PMC3244757] [PubMed: 21854979]
    478.
    Korlach J. and Turner S.W. (2012) Going beyond five bases in DNA sequencing. Current Opinion in Structural Biology 22: 251–261. [PubMed: 22575758]
    479.
    Sood A.J., Viner C. and Hoffman M.M. (2019) DNAmod: The DNA modification database. Journal of Cheminformatics 11: 30. [PMC free article: PMC6478773] [PubMed: 31016417]
    480.
    Chen C. et al. (2017) Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes. Proceedings of the National Academy of Sciences USA 114: 4501–4506. [PMC free article: PMC5410841] [PubMed: 28400512]
    481.
    Wion D. and Casadesús J. (2006) N6-methyl-adenine: An epigenetic signal for DNA–protein interactions. Nature Reviews Microbiology 4: 183–192. [PMC free article: PMC2755769] [PubMed: 16489347]
    482.
    Casadesús J. and Low D. (2006) Epigenetic gene regulation in the bacterial world. Microbiology and Molecular Biology Reviews 70: 830–856. [PMC free article: PMC1594586] [PubMed: 16959970]
    483.
    Blow M.J. et al. (2016) The epigenomic landscape of prokaryotes. PLOS Genetics 12: e1005854. [PMC free article: PMC4752239] [PubMed: 26870957]
    484.
    Adhikari S. and Curtis P.D. (2016) DNA methyltransferases and epigenetic regulation in bacteria. FEMS Microbiology Reviews 40: 575–591. [PubMed: 27476077]
    485.
    Hattman S. (2005) DNA-[adenine] methylation in lower eukaryotes. Biochemistry (Moscow) 70: 550–558. [PubMed: 15948708]
    486.
    Ma C. et al. (2019) N6-methyldeoxyadenine is a transgenerational epigenetic signal for mitochondrial stress adaptation. Nature Cell Biology 21: 319–327. [PubMed: 30510156]
    487.
    Fu Y. et al. (2015) N6-methyldeoxyadenosine marks active transcription start sites in Chlamydomonas. Cell 161: 879–892. [PMC free article: PMC4427561] [PubMed: 25936837]
    488.
    Zhang G. et al. (2015) N6-methyladenine DNA modification in Drosophila. Cell 161: 893–906. [PubMed: 25936838]
    489.
    Liu J. et al. (2016) Abundant DNA 6mA methylation during early embryogenesis of zebrafish and pig. Nature Communications 7: 13052. [PMC free article: PMC5059759] [PubMed: 27713410]
    490.
    Meyer K.D. and Jaffrey S.R. (2016) Expanding the diversity of DNA base modifications with N6-methyldeoxyadenosine. Genome Biology 17: 5. [PMC free article: PMC4712593] [PubMed: 26762117]
    491.
    Wu T.P. et al. (2016) DNA methylation on N6-adenine in mammalian embryonic stem cells. Nature 532: 329–333. [PMC free article: PMC4977844] [PubMed: 27027282]
    492.
    Li X. et al. (2019) The DNA modification N6-methyl-2′-deoxyadenosine (m6dA) drives activity-induced gene expression and is required for fear extinction. Nature Neuroscience 22: 534–544. [PMC free article: PMC6462436] [PubMed: 30778148]
    493.
    O’Brown Z.K. et al. (2019) Sources of artifact in measurements of 6mA and 4mC abundance in eukaryotic genomic DNA. BMC Genomics 20: 445. [PMC free article: PMC6547475] [PubMed: 31159718]
    494.
    Douvlataniotis K., Bensberg M., Lentini A., Gylemo B. and Nestor C.E. (2020) No evidence for DNA N6-methyladenine in mammals. Science Advances 6: eaay3335. [PMC free article: PMC7080441] [PubMed: 32206710]
    495.
    Fedoroff N.V. (1989) About maize transposable elements and development. Cell 56: 181–191. [PubMed: 2536297]
    496.
    Smith Z.D. and Meissner A. (2013) DNA methylation: Roles in mammalian development. Nature Reviews Genetics 14: 204–220. [PubMed: 23400093]
    497.
    Calarco J.P. et al. (2012) Reprogramming of DNA methylation in pollen guides epigenetic inheritance via small RNA. Cell 151: 194–205. [PMC free article: PMC3697483] [PubMed: 23000270]
    498.
    Law J.A. and Jacobsen S.E. (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nature Reviews Genetics 11: 204–220. [PMC free article: PMC3034103] [PubMed: 20142834]
    499.
    Zhang H., Lang Z. and Zhu J.-K. (2018) Dynamics and function of DNA methylation in plants. Nature Reviews Molecular Cell Biology 19: 489–506. [PubMed: 29784956]
    500.
    Chandler V.L. and Walbot V. (1986) DNA modification of a maize transposable element correlates with loss of activity. Proceedings of the National Academy of Sciences USA 83: 1767–1771. [PMC free article: PMC323165] [PubMed: 3006070]
    501.
    Chomet P.S., Wessler S. and Dellaporta S.L. (1987) Inactivation of the maize transposable element Activator (Ac) is associated with its DNA modification. EMBO Journal 6: 295–302. [PMC free article: PMC553394] [PubMed: 3034583]
    502.
    Regev A., Lamb M.J. and Jablonka E. (1998) The role of DNA methylation in invertebrates: Developmental regulation or genome defense? Molecular Biology and Evolution 15: 880–891.
    503.
    Dunwell T.L. and Pfeifer G.P. (2014) Drosophila genomic methylation: New evidence and new questions. Epigenomics 6: 459–461. [PMC free article: PMC4340582] [PubMed: 25431937]
    504.
    Tweedie S., Charlton J., Clark V. and Bird A. (1997) Methylation of genomes and genes at the invertebrate-vertebrate boundary. Molecular and Cellular Biology 17: 1469–1475. [PMC free article: PMC231872] [PubMed: 9032274]
    505.
    Riggs A.D. (1975) X inactivation, differentiation, and DNA methylation. Cytogenetics and Cell Genetics 14: 9–25. [PubMed: 1093816]
    506.
    Holliday R. and Pugh J.E. (1975) DNA modification mechanisms and gene activity during development. Science 187: 226–232. [PubMed: 1111098]
    507.
    Jiang L. et al. (2013) Sperm, but not oocyte, DNA methylome is inherited by zebrafish early embryos. Cell 153: 773–784. [PMC free article: PMC4081501] [PubMed: 23663777]
    508.
    Potok M.E., Nix D.A., Parnell T.J. and Cairns B.R. (2013) Reprogramming the maternal zebrafish genome after fertilization to match the paternal methylation pattern. Cell 153: 759–772. [PMC free article: PMC4030421] [PubMed: 23663776]
    509.
    Macleod D., Clark V.H. and Bird A. (1999) Absence of genome-wide changes in DNA methylation during development of the zebrafish. Nature Genetics 23: 139–140. [PubMed: 10508504]
    510.
    Ortega-Recalde O., Day R.C., Gemmell N.J. and Hore T.A. (2019) Zebrafish preserve global germline DNA methylation while sex-linked rDNA is amplified and demethylated during feminisation. Nature Communications 10: 3053. [PMC free article: PMC6635516] [PubMed: 31311924]
    511.
    Skvortsova K. et al. (2019) Retention of paternal DNA methylome in the developing zebrafish germline. Nature Communications 10: 3054. [PMC free article: PMC6624265] [PubMed: 31296860]
    512.
    Veenstra G.J.C. and Wolffe A.P. (2001) Constitutive genomic methylation during embryonic development of Xenopus. Biochimica et Biophysica Acta 1521: 39–44. [PubMed: 11690634]
    513.
    Lee Heather J., Hore Timothy A. and Reik W. (2014) Reprogramming the methylome: Erasing memory and creating diversity. Cell Stem Cell 14: 710–719. [PMC free article: PMC4051243] [PubMed: 24905162]
    514.
    Messerschmidt D.M., Knowles B.B. and Solter D. (2014) DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes & Development 28: 812–828. [PMC free article: PMC4003274] [PubMed: 24736841]
    515.
    Miyoshi N. et al. (2016) Erasure of DNA methylation, genomic imprints, and epimutations in a primordial germ-cell model derived from mouse pluripotent stem cells. Proceedings of the National Academy of Sciences USA 113: 9545–9550. [PMC free article: PMC5003264] [PubMed: 27486249]
    516.
    Zeng Y. and Chen T. (2019) DNA methylation reprogramming during mammalian development. Genes 10: 257. [PMC free article: PMC6523607] [PubMed: 30934924]
    517.
    Hackett J.A. and Surani M.A. (2013) DNA methylation dynamics during the mammalian life cycle. Philosophical Transactions of the Royal Society B: Biological Sciences 368: 20110328. [PMC free article: PMC3539357] [PubMed: 23166392]
    518.
    Li C. et al. (2018) DNA methylation reprogramming of functional elements during mammalian embryonic development. Cell Discovery 4: 41. [PMC free article: PMC6079081] [PubMed: 30109120]
    519.
    Jones P.A. and Taylor S.M. (1980) Cellular differentiation, cytidine analogs and DNA methylation. Cell 20: 85–93. [PubMed: 6156004]
    520.
    Carr B.I., Reilly J.G., Smith S.S., Winberg C. and Riggs A. (1984) The tumorigenicity of 5-azacytidine in the male Fischer rat. Carcinogenesis 5: 1583–1590. [PubMed: 6209028]
    521.
    Riggs A.D. (2002) X chromosome inactivation, differentiation, and DNA methylation revisited, with a tribute to Susumu Ohno. Cytogenetic and Genome Research 99: 17–24. [PubMed: 12900540]
    522.
    Hansen R.S. (2003) X inactivation-specific methylation of LINE-1 elements by DNMT3B: Implications for the Lyon repeat hypothesis. Human Molecular Genetics 12: 2559–2567. [PubMed: 12925568]
    523.
    Bird A., Taggart M., Frommer M., Miller O.J. and Macleod D. (1985) A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell 40: 91–99. [PubMed: 2981636]
    524.
    Wutz A. et al. (1997) Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389: 745–749. [PubMed: 9338788]
    525.
    Smilinich N.J. et al. (1999) A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. Proceedings of the National Academy of Sciences USA 96: 8064–8069. [PMC free article: PMC22188] [PubMed: 10393948]
    526.
    Bird A. (2002) DNA methylation patterns and epigenetic memory. Genes & Development 16: 6–21. [PubMed: 11782440]
    527.
    Deaton A.M. and Bird A. (2011) CpG islands and the regulation of transcription. Genes & Development 25: 1010–1022. [PMC free article: PMC3093116] [PubMed: 21576262]
    528.
    Deniz Ö., Frost J.M. and Branco M.R. (2019) Regulation of transposable elements by DNA modifications. Nature Reviews Genetics 20: 417–431. [PubMed: 30867571]
    529.
    Saxonov S., Berg P. and Brutlag D.L. (2006) A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proceedings of the National Academy of Sciences USA 103: 1412–1417. [PMC free article: PMC1345710] [PubMed: 16432200]
    530.
    Fuks F. et al. (2003) The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. Journal of Biological Chemistry 278: 4035–4040. [PubMed: 12427740]
    531.
    Rose N.R. and Klose R.J. (2014) Understanding the relationship between DNA methylation and histone lysine methylation. Biochimica et Biophysica Acta 1839: 1362–1372. [PMC free article: PMC4316174] [PubMed: 24560929]
    532.
    Bird A.P. (1986) CpG-rich islands and the function of DNA methylation. Nature 321: 209–213. [PubMed: 2423876]
    533.
    Gardiner-Garden M. and Frommer M. (1987) CpG islands in vertebrate genomes. Journal of Molecular Biology 196: 261–282. [PubMed: 3656447]
    534.
    Brinkman A.B. et al. (2012) Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk. Genome Research 22: 1128–1138. [PMC free article: PMC3371717] [PubMed: 22466170]
    535.
    Vavouri T. and Lehner B. (2012) Human genes with CpG island promoters have a distinct transcription-associated chromatin organization. Genome Biology 13: R110. [PMC free article: PMC3580500] [PubMed: 23186133]
    536.
    Jeziorska D.M. et al. (2017) DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease. Proceedings of the National Academy of Sciences USA 114: E7526–35. [PMC free article: PMC5594649] [PubMed: 28827334]
    537.
    Weinberg D.N. et al. (2019) The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape. Nature 573: 281–286. [PMC free article: PMC6742567] [PubMed: 31485078]
    538.
    Zaghi M., Broccoli V. and Sessa A. (2020) H3K36 methylation in neural development and associated diseases. Frontiers in Genetics 10: 1291. [PMC free article: PMC6962298] [PubMed: 31998360]
    539.
    Huff J.T. and Zilberman D. (2014) Dnmt1-independent CG methylation contributes to nucleosome positioning in diverse eukaryotes. Cell 156: 1286–1297. [PMC free article: PMC3969382] [PubMed: 24630728]
    540.
    Lev Maor G., Yearim A. and Ast G. (2015) The alternative role of DNA methylation in splicing regulation. Trends in Genetics 31: 274–280. [PubMed: 25837375]
    541.
    Jadhav U. et al. (2019) Extensive recovery of embryonic enhancer and gene memory stored in hypomethylated enhancer DNA. Molecular Cell 74: 542–554. [PMC free article: PMC6499659] [PubMed: 30905509]
    542.
    Reizel Y. et al. (2021) FoxA-dependent demethylation of DNA initiates epigenetic memory of cellular identity. Developmental Cell 56: 602–612. [PMC free article: PMC8129911] [PubMed: 33636105]
    543.
    Li E., Bestor T.H. and Jaenisch R. (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69: 915–926. [PubMed: 1606615]
    544.
    Okano M., Bell D.W., Haber D.A. and Li E. (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99: 247–257. [PubMed: 10555141]
    545.
    Cui D. and Xu X. (2018) DNA methyltransferases, DNA methylation, and age-associated cognitive function. International Journal of Molecular Sciences 19: 1315. [PMC free article: PMC5983821] [PubMed: 29710796]
    546.
    Nishiyama A. et al. (2013) Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication. Nature 502: 249–253. [PubMed: 24013172]
    547.
    Métivier R. et al. (2008) Cyclical DNA methylation of a transcriptionally active promoter. Nature 452: 45–50. [PubMed: 18322525]
    548.
    Kangaspeska S. et al. (2008) Transient cyclical methylation of promoter DNA. Nature 452: 112–115. [PubMed: 18322535]
    549.
    Miller C.A. and Sweatt J.D. (2007) Covalent modification of DNA regulates memory formation. Neuron 53: 857–869. [PubMed: 17359920]
    550.
    Ip J.P.K., Mellios N. and Sur M. (2018) Rett syndrome: Insights into genetic, molecular and circuit mechanisms. Nature Reviews Neuroscience 19: 368–382. [PMC free article: PMC6402579] [PubMed: 29740174]
    551.
    de Mendoza A. et al. (2021) The emergence of the brain non-CpG methylation system in vertebrates. Nature Ecology & Evolution 5: 369–378. [PMC free article: PMC7116863] [PubMed: 33462491]
    552.
    Goll M.G. et al. (2006) Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311: 395–398. [PubMed: 16424344]
    553.
    Rai K. et al. (2007) Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish. Genes & Development 21: 261–266. [PMC free article: PMC1785123] [PubMed: 17289917]
    554.
    Jeltsch A. et al. (2017) Mechanism and biological role of Dnmt2 in nucleic acid methylation. RNA Biology 14: 1108–1123. [PMC free article: PMC5699548] [PubMed: 27232191]
    555.
    Tahiliani M. et al. (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324: 930–935. [PMC free article: PMC2715015] [PubMed: 19372391]
    556.
    Ito S. et al. (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333: 1300–1303. [PMC free article: PMC3495246] [PubMed: 21778364]
    557.
    Ito S. et al. (2010) Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466: 1129–1133. [PMC free article: PMC3491567] [PubMed: 20639862]
    558.
    Yang J., Bashkenova N., Zang R., Huang X. and Wang J. (2020) The roles of TET family proteins in development and stem cells. Development 147: dev183129. [PMC free article: PMC6983710] [PubMed: 31941705]
    559.
    Lu F., Liu Y., Jiang L., Yamaguchi S. and Zhang Y. (2014) Role of Tet proteins in enhancer activity and telomere elongation. Genes & Development 28: 2103–2119. [PMC free article: PMC4180973] [PubMed: 25223896]
    560.
    Costa Y. et al. (2013) NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 495: 370–374. [PMC free article: PMC3606645] [PubMed: 23395962]
    561.
    Dixon G. et al. (2021) QSER1 protects DNA methylation valleys from de novo methylation. Science 372: eabd0875. [PMC free article: PMC8185639] [PubMed: 33833093]
    562.
    Gu T. and Goodell M.A. (2021) The push and pull of DNA methylation. Science 372: 128–129. [PubMed: 33833110]
    563.
    Kriaucionis S. and Heintz N. (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324: 929–930. [PMC free article: PMC3263819] [PubMed: 19372393]
    564.
    Antunes C. et al. (2021) Tet3 ablation in adult brain neurons increases anxiety-like behavior and regulates cognitive function in mice. Molecular Psychiatry 26: 1445–1457. [PubMed: 32103150]
    565.
    Li X. et al. (2014) Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proceedings of the National Academy of Sciences USA 111: 7120–7125. [PMC free article: PMC4024925] [PubMed: 24757058]
    566.
    Yu H. et al. (2015) Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair. Nature Neuroscience 18: 836–843. [PMC free article: PMC4446239] [PubMed: 25915473]
    567.
    Frommer M. et al. (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proceedings of the National Academy of Sciences USA 89: 1827–1831. [PMC free article: PMC48546] [PubMed: 1542678]
    568.
    Clark S.J., Harrison J., Paul C.L. and Frommer M. (1994) High sensitivity mapping of methylated cytosines. Nucleic acids research 22: 2990–2997. [PMC free article: PMC310266] [PubMed: 8065911]
    569.
    Simpson J.T. et al. (2017) Detecting DNA cytosine methylation using nanopore sequencing. Nature Methods 14: 407–410. [PubMed: 28218898]
    570.
    Rand A.C. et al. (2017) Mapping DNA methylation with high-throughput nanopore sequencing. Nature methods 14: 411–413. [PMC free article: PMC5704956] [PubMed: 28218897]
    571.
    Swallow D.M. and Troelsen J.T. (2016) Escape from epigenetic silencing of lactase expression is triggered by a single-nucleotide change. Nature Structural & Molecular Biology 23: 505–507. [PubMed: 27273635]
    572.
    Horvath S. (2013) DNA methylation age of human tissues and cell types. Genome Biology 14: R115. [PMC free article: PMC4015143] [PubMed: 24138928]
    573.
    Wagner W. (2017) Epigenetic aging clocks in mice and men. Genome Biology 18: 107. [PMC free article: PMC5470213] [PubMed: 28615041]
    574.
    Boix C.A., James B.T., Park Y.P., Meuleman W. and Kellis M. (2021) Regulatory genomic circuitry of human disease loci by integrative epigenomics. Nature 590: 300–307. [PMC free article: PMC7875769] [PubMed: 33536621]
    575.
    Lin X. et al. (2020) Genome-wide analysis of aberrant methylation of enhancer DNA in human osteoarthritis. BMC Medical Genomics 13: 1. [PMC free article: PMC6942377] [PubMed: 31900157]
    576.
    Bartosovic M., Kabbe M. and Castelo-Branco G. (2021) Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues. Nature Biotechnology 39: 825–835. [PMC free article: PMC7611252] [PubMed: 33846645]
    577.
    Wu S.J. et al. (2021) Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression. Nature Biotechnology 39: 819–824. [PMC free article: PMC8277750] [PubMed: 33846646]
    578.
    Näär A.M., Lemon B.D. and Tjian R. (2001) Transcriptional coactivator complexes. Annual Review of Biochemistry 70: 475–501. [PubMed: 11395415]
    579.
    Iwafuchi-Doi M. and Zaret K.S. (2014) Pioneer transcription factors in cell reprogramming. Genes & Development 28: 2679–2692. [PMC free article: PMC4265672] [PubMed: 25512556]
    580.
    Soufi A. et al. (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161: 555–568. [PMC free article: PMC4409934] [PubMed: 25892221]
    581.
    Iwafuchi-Doi M. (2019) The mechanistic basis for chromatin regulation by pioneer transcription factors. WIREs Systems Biology and Medicine 11: e1427. [PMC free article: PMC6585746] [PubMed: 29949240]

    Chapter 15

    1.
    Maturana H.R. and Varela F.J. (1972) Autopoiesis and Cognition: The Realization of the Living (D. Reidel Publishing Company, New York).
    2.
    Ohtomo Y., Kakegawa T., Ishida A., Nagase T. and Rosing M.T. (2014) Evidence for biogenic graphite in early Archaean Isua metasedimentary rocks. Nature Geoscience 7: 25–28.
    3.
    Hoyle F. and Wickramasinghe N.C. (1986) The case for life as a cosmic phenomenon. Nature 322: 509–511.
    4.
    Pelletier J.F. et al. (2021) Genetic requirements for cell division in a genomically minimal cell. Cell 184: 2430–2440. [PubMed: 33784496]
    5.
    Etchegaray E., Naville M., Volff J.-N. and Haftek-Terreau Z. (2021) Transposable element-derived sequences in vertebrate development. Mobile DNA 12: 1. [PMC free article: PMC7786948] [PubMed: 33407840]
    6.
    Cosby R.L. et al. (2021) Recurrent evolution of vertebrate transcription factors by transposase capture. Science 371: eabc6405. [PMC free article: PMC8186458] [PubMed: 33602827]
    7.
    Wang K. et al. (2021) African lungfish genome sheds light on the vertebrate water-to-land transition. Cell 184: 1362–1376. [PubMed: 33545087]
    8.
    van de Lagemaat L.N., Landry J.-R., Mager D.L. and Medstrand P. (2003) Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends in Genetics 19: 530–536. [PubMed: 14550626]
    9.
    Roller M. et al. (2021) LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions. Genome Biology 22: 62. [PMC free article: PMC7890895] [PubMed: 33602314]
    10.
    Jacques P.-É., Jeyakani J. and Bourque G. (2013) The majority of primate-specific regulatory sequences are derived from transposable elements. PLOS Genetics 9: e1003504. [PMC free article: PMC3649963] [PubMed: 23675311]
    11.
    Trizzino M. et al. (2017) Transposable elements are the primary source of novelty in primate gene regulation. Genome Research 27: 1623–1633. [PMC free article: PMC5630026] [PubMed: 28855262]
    12.
    Bianconi E. et al. (2013) An estimation of the number of cells in the human body. Annals of Human Biology 40: 463–471. [PubMed: 23829164]
    13.
    Sender R., Fuchs S. and Milo R. (2016) Revised estimates for the number of human and bacteria cells in the body. PLOS Biology 14: e1002533. [PMC free article: PMC4991899] [PubMed: 27541692]
    14.
    Rivron N.C. et al. (2018) Blastocyst-like structures generated solely from stem cells. Nature 557: 106–111. [PubMed: 29720634]
    15.
    Sozen B. et al. (2018) Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures. Nature Cell Biology 20: 979–989. [PubMed: 30038254]
    16.
    Li R. et al. (2019) Generation of blastocyst-like structures from mouse embryonic and adult cell cultures. Cell 179: 687–702. [PMC free article: PMC7359735] [PubMed: 31626770]
    17.
    Yu L. et al. (2021) Blastocyst-like structures generated from human pluripotent stem cells. Nature 591: 620–626. [PubMed: 33731924]
    18.
    Liu X. et al. (2021) Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature 591: 627–632. [PubMed: 33731926]
    19.
    Clevers H. (2016) Modeling development and disease with organoids. Cell 165: 1586–1597. [PubMed: 27315476]
    20.
    Kim J., Koo B.-K. and Knoblich J.A. (2020) Human organoids: Model systems for human biology and medicine. Nature Reviews Molecular Cell Biology 21: 571–584. [PMC free article: PMC7339799] [PubMed: 32636524]
    21.
    Matthews K.R.W. et al. (2021) Rethinking human embryo research policies. Hastings Center Report 51: 47–51. [PMC free article: PMC7986614] [PubMed: 33630327]
    22.
    Miller A.J. et al. (2019) Generation of lung organoids from human pluripotent stem cells in vitro. Nature Protocols 14: 518–540. [PMC free article: PMC6531049] [PubMed: 30664680]
    23.
    Prior N., Inacio P. and Huch M. (2019) Liver organoids: From basic research to therapeutic applications. Gut 68: 2228–2237. [PMC free article: PMC6872443] [PubMed: 31300517]
    24.
    Pleguezuelos-Manzano C. et al. (2020) Establishment and culture of human intestinal organoids derived from adult stem cells. Current Protocols in Immunology 130: e106. [PMC free article: PMC9285512] [PubMed: 32940424]
    25.
    Sato T. et al. (2011) Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and barrett’s epithelium. Gastroenterology 141: 1762–1772. [PubMed: 21889923]
    26.
    Nishinakamura R. (2019) Human kidney organoids: Progress and remaining challenges. Nature Reviews Nephrology 15: 613–624. [PubMed: 31383997]
    27.
    O‘Hara-Wright M. and Gonzalez-Cordero A. (2020) Retinal organoids: A window into human retinal development. Development 147: dev189746. [PMC free article: PMC7774906] [PubMed: 33361444]
    28.
    Lancaster M.A. et al. (2013) Cerebral organoids model human brain development and microcephaly. Nature 501: 373–379. [PMC free article: PMC3817409] [PubMed: 23995685]
    29.
    Luo C. et al. (2016) Cerebral organoids recapitulate epigenomic signatures of the human fetal brain. Cell Reports 17: 3369–3384. [PMC free article: PMC5495578] [PubMed: 28009303]
    30.
    Lancaster M.A. et al. (2017) Guided self-organization and cortical plate formation in human brain organoids. Nature Biotechnology 35: 659–666. [PMC free article: PMC5824977] [PubMed: 28562594]
    31.
    Sachs N., Tsukamoto Y., Kujala P., Peters P.J. and Clevers H. (2017) Intestinal epithelial organoids fuse to form self-organizing tubes in floating collagen gels. Development 144: 1107–1112. [PubMed: 28292848]
    32.
    Giandomenico S.L. et al. (2019) Cerebral organoids at the air–liquid interface generate diverse nerve tracts with functional output. Nature Neuroscience 22: 669–679. [PMC free article: PMC6436729] [PubMed: 30886407]
    33.
    Pellegrini L. et al. (2020) Human CNS barrier-forming organoids with cerebrospinal fluid production. Science 369: eaaz5626. [PMC free article: PMC7116154] [PubMed: 32527923]
    34.
    Benito-Kwiecinski S. et al. (2021) An early cell shape transition drives evolutionary expansion of the human forebrain. Cell 184: 2084–2102. [PMC free article: PMC8054913] [PubMed: 33765444]
    35.
    Korpal M., Lee E.S., Hu G. and Kang Y. (2008) The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. Journal of Biological Chemistry 283: 14910–14914. [PMC free article: PMC3258899] [PubMed: 18411277]
    36.
    Beltran M. et al. (2008) A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes & Development 22: 756–769. [PMC free article: PMC2275429] [PubMed: 18347095]
    37.
    Bernardes de Jesus B. et al. (2018) Silencing of the lncRNA Zeb2-NAT facilitates reprogramming of aged fibroblasts and safeguards stem cell pluripotency. Nature Communications 9: 94. [PMC free article: PMC5758807] [PubMed: 29311544]
    38.
    Chen X. et al. (2016) Upregulation of long noncoding RNA HOTTIP promotes metastasis of esophageal squamous cell carcinoma via induction of EMT. Oncotarget 7: 84480–84485. [PMC free article: PMC5356674] [PubMed: 27806322]
    39.
    Xu Q. et al. (2016) Long non-coding RNA regulation of epithelial–mesenchymal transition in cancer metastasis. Cell Death & Disease 7: e2254. [PMC free article: PMC5143379] [PubMed: 27277676]
    40.
    Shen X. et al. (2020) The long noncoding RNA TUG1 is required for TGF-β/TWIST1/EMT-mediated metastasis in colorectal cancer cells. Cell Death & Disease 11: 65. [PMC free article: PMC6985237] [PubMed: 31988275]
    41.
    Xiong T. et al. (2020) LncRNA NRON promotes the proliferation, metastasis and EMT process in bladder cancer. Journal of Cancer 11: 1751–1760. [PMC free article: PMC7052857] [PubMed: 32194786]
    42.
    Eze U.C., Bhaduri A., Haeussler M., Nowakowski T.J. and Kriegstein A.R. (2021) Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia. Nature Neuroscience 24: 584–594. [PMC free article: PMC8012207] [PubMed: 33723434]
    43.
    Heintzman N.D. et al. (2009) Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459: 108–112. [PMC free article: PMC2910248] [PubMed: 19295514]
    44.
    Waddington C.H. (1957) The Strategy of the Genes: A Discussion of Some Aspects of Theoretical Biology (George Allen and Unwin, New York).
    45.
    Reilly M.B., Cros C., Varol E., Yemini E. and Hobert O. (2020) Unique homeobox codes delineate all the neuron classes of C. elegans. Nature 584: 595–601. [PMC free article: PMC7587405] [PubMed: 32814896]
    46.
    Rinn J.L., Bondre C., Gladstone H.B., Brown P.O. and Chang H.Y. (2006) Anatomic demarcation by positional variation in fibroblast gene expression programs. PLOS Genetics 2: e119. [PMC free article: PMC1523235] [PubMed: 16895450]
    47.
    Rinn J.L. et al. (2008) A dermal HOX transcriptional program regulates site-specific epidermal fate. Genes & Development 22: 303–307. [PMC free article: PMC2216690] [PubMed: 18245445]
    48.
    Frank-Bertoncelj M. et al. (2017) Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions. Nature Communications 8: 14852. [PMC free article: PMC5376654] [PubMed: 28332497]
    49.
    Marioni J.C. and Arendt D. (2017) How single-cell genomics is changing evolutionary and developmental biology. Annual Review of Cell and Developmental Biology 33: 537–553. [PubMed: 28813177]
    50.
    Arendt D., Bertucci P.Y., Achim K. and Musser J.M. (2019) Evolution of neuronal types and families. Current Opinion in Neurobiology 56: 144–152. [PMC free article: PMC6556553] [PubMed: 30826503]
    51.
    Vinogradov A.E. and Anatskaya O.V. (2007) Organismal complexity, cell differentiation and gene expression: Human over mouse. Nucleic Acids Research 35: 6350–6356. [PMC free article: PMC2095826] [PubMed: 17881362]
    52.
    Shapiro E., Biezuner T. and Linnarsson S. (2013) Single-cell sequencing-based technologies will revolutionize whole-organism science. Nature Reviews Genetics 14: 618–630. [PubMed: 23897237]
    53.
    Stuart T. and Satija R. (2019) Integrative single-cell analysis. Nature Reviews Genetics 20: 257–272. [PubMed: 30696980]
    54.
    Kashima Y. et al. (2020) Single-cell sequencing techniques from individual to multiomics analyses. Experimental & Molecular Medicine 52: 1419–1427. [PMC free article: PMC8080663] [PubMed: 32929221]
    55.
    Sagar and Grün D. (2020) Deciphering cell fate decision by integrated single-cell sequencing analysis. Annual Review of Biomedical Data Science 3: 1–22. [PMC free article: PMC7115822] [PubMed: 32780577]
    56.
    Cardona-Alberich A., Tourbez M., Pearce S.F. and Sibley C.R. (2021) Elucidating the cellular dynamics of the brain with single-cell RNA sequencing. RNA Biology 18: 1063–1084. [PMC free article: PMC8216183] [PubMed: 33499699]
    57.
    Sladitschek H.L. et al. (2020) MorphoSeq: Full single-cell transcriptome dynamics up to gastrulation in a chordate. Cell 181: 922–935. [PMC free article: PMC7237864] [PubMed: 32315617]
    58.
    Lencer E., Prekeris R. and Artinger K.B. (2021) Single-cell RNA analysis identifies pre-migratory neural crest cells expressing markers of differentiated derivatives. eLife 10: e66078. [PMC free article: PMC8367380] [PubMed: 34397384]
    59.
    Fang R. et al. (2021) Comprehensive analysis of single cell ATAC-seq data with SnapATAC. Nature Communications 12: 1337. [PMC free article: PMC7910485] [PubMed: 33637727]
    60.
    Kelley D. and Rinn J. (2012) Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biology 13: R107. [PMC free article: PMC3580499] [PubMed: 23181609]
    61.
    Kelley D.R., Hendrickson D.G., Tenen D. and Rinn J.L. (2014) Transposable elements modulate human RNA abundance and splicing via specific RNA-protein interactions. Genome Biology 15: 537. [PMC free article: PMC4272801] [PubMed: 25572935]
    62.
    Kim Daniel H. et al. (2015) Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression during reprogramming. Cell Stem Cell 16: 88–101. [PMC free article: PMC4291542] [PubMed: 25575081]
    63.
    Ma Q. and Chang H.Y. (2016) Single-cell profiling of lncRNAs in the developing human brain. Genome Biology 17: 68. [PMC free article: PMC4831122] [PubMed: 27079200]
    64.
    Liu S.J. et al. (2016) Single-cell analysis of long non-coding RNAs in the developing human neocortex. Genome Biology 17: 67. [PMC free article: PMC4831157] [PubMed: 27081004]
    65.
    Tasic B. et al. (2018) Shared and distinct transcriptomic cell types across neocortical areas. Nature 563: 72–78. [PMC free article: PMC6456269] [PubMed: 30382198]
    66.
    Alessio E. et al. (2019) Single cell analysis reveals the involvement of the long non-coding RNA Pvt1 in the modulation of muscle atrophy and mitochondrial network. Nucleic Acids Research 47: 1653–1670. [PMC free article: PMC6393313] [PubMed: 30649422]
    67.
    Bakken T.E. et al. (2021) Comparative cellular analysis of motor cortex in human, marmoset and mouse. Nature 598: 111–119. [PMC free article: PMC8494640] [PubMed: 34616062]
    68.
    Bocchi V.D. et al. (2021) The coding and long noncoding single-cell atlas of the developing human fetal striatum. Science 372: eabf5759. [PubMed: 33958447]
    69.
    Manji S.S. et al. (2006) Molecular characterization and expression of maternally expressed gene 3 (Meg3/Gtl2) RNA in the mouse inner ear. Journal of Neuroscience Research 83: 181–190. [PubMed: 16342203]
    70.
    Moradi Chameh H. et al. (2021) Diversity amongst human cortical pyramidal neurons revealed via their sag currents and frequency preferences. Nature Communications 12: 2497. [PMC free article: PMC8093195] [PubMed: 33941783]
    71.
    Bray S.J. (2016) Notch signalling in context. Nature Reviews Molecular Cell Biology 17: 722–735. [PubMed: 27507209]
    72.
    Oh E.C. and Katsanis N. (2012) Cilia in vertebrate development and disease. Development 139: 443–448. [PMC free article: PMC3275291] [PubMed: 22223675]
    73.
    Guignard L. et al. (2020) Contact area–dependent cell communication and the morphological invariance of ascidian embryogenesis. Science 369: eaar5663. [PubMed: 32646972]
    74.
    Priya R. et al. (2020) Tension heterogeneity directs form and fate to pattern the myocardial wall. Nature 588: 130–134. [PubMed: 33208950]
    75.
    Levin M. (2021) Bioelectric signaling: Reprogrammable circuits underlying embryogenesis, regeneration, and cancer. Cell 184: 1971–1989. [PubMed: 33826908]
    76.
    Zepp J.A. et al. (2021) Genomic, epigenomic, and biophysical cues controlling the emergence of the lung alveolus. Science 371: eabc3172. [PMC free article: PMC8320017] [PubMed: 33707239]
    77.
    Mallo M. and Alonso C.R. (2013) The regulation of Hox gene expression during animal development. Development 140: 3951–3963. [PubMed: 24046316]
    78.
    Wolpert L. (1969) Positional information and the spatial pattern of cellular differentiation. Journal of Theoretical Biology 25: 1–47. [PubMed: 4390734]
    79.
    Sulston J.E. and Horvitz H.R. (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental Biology 56: 110–156. [PubMed: 838129]
    80.
    Sulston J.E., Schierenberg E., White J.G. and Thomson J.N. (1983) The embryonic cell lineage of the nematode Caenorhabditis elegans. Developmental Biology 100: 64–119. [PubMed: 6684600]
    81.
    Kemphues K.J. (2016) Horvitz and Sulston on Caenorhabditis elegans cell lineage mutants. Genetics 203: 1485–1487. [PMC free article: PMC4981256] [PubMed: 27516609]
    82.
    Hobert O. (2010) Neurogenesis in the nematode Caenorhabditis elegans, in Wormbook: The Online Review of C. elegans biology. http://www​.wormbook.org. [PMC free article: PMC4791530] [PubMed: 20891032]
    83.
    Jonsson H. et al. (2021) Differences between germline genomes of monozygotic twins. Nature Genetics 53: 27–34. [PubMed: 33414551]
    84.
    Witherspoon D.J. et al. (2007) Genetic similarities within and between human populations. Genetics 176: 351–359. [PMC free article: PMC1893020] [PubMed: 17339205]
    85.
    Huynh J.-R. and St Johnston D. (2004) The origin of asymmetry: Early polarisation of the Drosophila germline cyst and oocyte. Current Biology 14: R438–49. [PubMed: 15182695]
    86.
    Chen Q., Shi J., Tao Y. and Zernicka-Goetz M. (2018) Tracing the origin of heterogeneity and symmetry breaking in the early mammalian embryo. Nature Communications 9: 1819. [PMC free article: PMC5940674] [PubMed: 29739935]
    87.
    Jankele R., Jelier R. and Gönczy P. (2021) Physically asymmetric division of the C. elegans zygote ensures invariably successful embryogenesis. eLife 10: e61714. [PMC free article: PMC7972452] [PubMed: 33620314]
    88.
    Sunchu B. and Cabernard C. (2020) Principles and mechanisms of asymmetric cell division. Development 147: dev167650. [PMC free article: PMC7338270] [PubMed: 32601056]
    89.
    Cardelli L., Csikász-Nagy A., Dalchau N., Tribastone M. and Tschaikowski M. (2016) Noise reduction in complex biological switches. Scientific Reports 6: 20214. [PMC free article: PMC4745012] [PubMed: 26853830]
    90.
    Klosin A. et al. (2020) Phase separation provides a mechanism to reduce noise in cells. Science 367: 464–468. [PubMed: 31974256]
    91.
    Exelby K. et al. (2021) Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks. Development 148: dev197566. [PMC free article: PMC7929933] [PubMed: 33547135]
    92.
    Block F.E. (1987) Analog and digital computer theory. International Journal of Clinical Monitoring and Computing 4: 47–51. [PubMed: 3572195]
    93.
    Wong E.S. et al. (2015) Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals. Genome Research 25: 167–178. [PMC free article: PMC4315291] [PubMed: 25394363]
    94.
    Berthelot C., Villar D., Horvath J.E., Odom D.T. and Flicek P. (2018) Complexity and conservation of regulatory landscapes underlie evolutionary resilience of mammalian gene expression. Nature Ecology & Evolution 2: 152–163. [PMC free article: PMC5733139] [PubMed: 29180706]
    95.
    Peterson K.J., Dietrich M.R. and McPeek M.A. (2009) MicroRNAs and metazoan macroevolution: Insights into canalization, complexity, and the Cambrian explosion. BioEssays 31: 736–747. [PubMed: 19472371]
    96.
    Ebert M.S. and Sharp P.A. (2012) Roles for microRNAs in conferring robustness to biological processes. Cell 149: 515–524. [PMC free article: PMC3351105] [PubMed: 22541426]
    97.
    Plavskin Y. et al. (2016) Ancient trans-acting siRNAs confer robustness and sensitivity onto the auxin response. Developmental Cell 36: 276–289. [PMC free article: PMC5444541] [PubMed: 26859352]
    98.
    Hong J.-W., Hendrix D.A. and Levine M.S. (2008) Shadow enhancers as a source of evolutionary novelty. Science 321: 1314. [PMC free article: PMC4257485] [PubMed: 18772429]
    99.
    Cannavò E. et al. (2016) Shadow enhancers are pervasive features of developmental regulatory networks. Current Biology 26: 38–51. [PMC free article: PMC4712172] [PubMed: 26687625]
    100.
    Osterwalder M. et al. (2018) Enhancer redundancy provides phenotypic robustness in mammalian development. Nature 554: 239–243. [PMC free article: PMC5808607] [PubMed: 29420474]
    101.
    Waymack R., Fletcher A., Enciso G. and Wunderlich Z. (2020) Shadow enhancers can suppress input transcription factor noise through distinct regulatory logic. eLife 9: e59351. [PMC free article: PMC7556877] [PubMed: 32804082]
    102.
    Kvon E.Z., Waymack R., Gad M. and Wunderlich Z. (2021) Enhancer redundancy in development and disease. Nature Reviews Genetics 22: 324–336. [PMC free article: PMC8068586] [PubMed: 33442000]
    103.
    Sultana T., Zamborlini A., Cristofari G. and Lesage P. (2017) Integration site selection by retroviruses and transposable elements in eukaryotes. Nature Reviews Genetics 18: 292–308. [PubMed: 28286338]
    104.
    Barth N.K.H., Li L. and Taher L. (2020) Independent transposon exaptation is a widespread mechanism of redundant enhancer evolution in the mammalian genome. Genome Biology and Evolution 12: 1–17. [PMC free article: PMC7093719] [PubMed: 31950992]
    105.
    McKinley K.L. and Cheeseman I.M. (2016) The molecular basis for centromere identity and function. Nature Reviews Molecular Cell Biology 17: 16–29. [PMC free article: PMC8603311] [PubMed: 26601620]
    106.
    Trivedi P. et al. (2019) The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex. Nature Structural & Molecular Biology 21: 1127–1137. [PMC free article: PMC7341897] [PubMed: 31481798]
    107.
    Hartley G. and O‘Neill R.J. (2019) Centromere repeats: Hidden gems of the genome. Genes 10: 223. [PMC free article: PMC6471113] [PubMed: 30884847]
    108.
    Zackroff R.V., Rosenfeld A.C. and Weisenberg R.C. (1976) Effects of RNase and RNA on in vitro aster assembly. Journal of Supramolecular Structure 5: 577–589. [PubMed: 1027923]
    109.
    Topp C.N., Zhong C.X. and Dawe R.K. (2004) Centromere-encoded RNAs are integral components of the maize kinetochore. Proceedings of the National Academy of Sciences USA 101: 15986–15991. [PMC free article: PMC528775] [PubMed: 15514020]
    110.
    Folco H.D., Pidoux A.L., Urano T. and Allshire R.C. (2008) Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres. Science 319: 94–97. [PMC free article: PMC2586718] [PubMed: 18174443]
    111.
    Wong L.H. et al. (2007) Centromere RNA is a key component for the assembly of nucleoproteins at the nucleolus and centromere. Genome Research 17: 1146–1160. [PMC free article: PMC1933521] [PubMed: 17623812]
    112.
    Li F., Sonbuchner L., Kyes S.A., Epp C. and Deitsch K.W. (2008) Nuclear non-coding RNAs are transcribed from the centromeres of Plasmodium falciparum and are associated with centromeric chromatin. Journal of Biological Chemistry 283: 5692–5698. [PubMed: 18165241]
    113.
    Ferri F., Bouzinba-Segard H., Velasco G., Hubé F. and Francastel C. (2009) Non-coding murine centromeric transcripts associate with and potentiate Aurora B kinase. Nucleic Acids Research 37: 5071–5080. [PMC free article: PMC2731909] [PubMed: 19542185]
    114.
    Malik H.S. and Henikoff S. (2009) Major evolutionary transitions in centromere complexity. Cell 138: 1067–1082. [PubMed: 19766562]
    115.
    Alliegro M.C. (2011) The centrosome and spindle as a ribonucleoprotein complex. Chromosome Research 19: 367–376. [PubMed: 21287260]
    116.
    Zwicker D., Decker M., Jaensch S., Hyman A.A. and Jülicher F. (2014) Centrosomes are autocatalytic droplets of pericentriolar material organized by centrioles. Proceedings of the National Academy of Sciences USA 111: E2636–45. [PMC free article: PMC4084434] [PubMed: 24979791]
    117.
    Rošić S., Köhler F. and Erhardt S. (2014) Repetitive centromeric satellite RNA is essential for kinetochore formation and cell division. Journal of Cell Biology 207: 335–349. [PMC free article: PMC4226727] [PubMed: 25365994]
    118.
    Quénet D. and Dalal Y. (2014) A long non-coding RNA is required for targeting centromeric protein A to the human centromere. eLife 3: e26016. [PMC free article: PMC4145801] [PubMed: 25117489]
    119.
    Rošić S. and Erhardt S. (2016) No longer a nuisance: Long non-coding RNAs join CENP-A in epigenetic centromere regulation. Cellular and Molecular Life Sciences 73: 1387–1398. [PubMed: 26748759]
    120.
    Mutazono M. et al. (2017) The intron in centromeric noncoding RNA facilitates RNAi-mediated formation of heterochromatin. PLOS Genetics 13: e1006606. [PMC free article: PMC5322907] [PubMed: 28231281]
    121.
    Smurova K. and De Wulf P. (2018) Centromere and pericentromere transcription: Roles and regulation … in sickness and in health. Frontiers in Genetics 9: 674. [PMC free article: PMC6309819] [PubMed: 30627137]
    122.
    Ling Y.H. and Yuen K.W.Y. (2019) Point centromere activity requires an optimal level of centromeric noncoding RNA. Proceedings of the National Academy of Sciences USA 116: 6270–6279. [PMC free article: PMC6442628] [PubMed: 30850541]
    123.
    Bergalet J. et al. (2020) Inter-dependent centrosomal co-localization of the cen and ik2 cis-natural antisense mRNAs in Drosophila. Cell Reports 30: 3339–3352. [PubMed: 32160541]
    124.
    Habermann K. and Lange B.M.H. (2012) New insights into subcomplex assembly and modifications of centrosomal proteins. Cell Division 7: 17. [PMC free article: PMC3479078] [PubMed: 22800182]
    125.
    Chavali P.L., Pütz M. and Gergely F. (2014) Small organelle, big responsibility: The role of centrosomes in development and disease. Philosophical Transactions of the Royal Society B: Biological Sciences 369: 20130468. [PMC free article: PMC4113112] [PubMed: 25047622]
    126.
    Conduit P.T., Wainman A. and Raff J.W. (2015) Centrosome function and assembly in animal cells. Nature Reviews Molecular Cell Biology 16: 611–624. [PubMed: 26373263]
    127.
    Joukov V. and De Nicolo A. (2019) The centrosome and the primary cilium: The yin and yang of a hybrid organelle. Cells 8: 701. [PMC free article: PMC6678760] [PubMed: 31295970]
    128.
    Métivier R. et al. (2003) Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115: 751–763. [PubMed: 14675539]
    129.
    Niklas K.J. (2014) The evolutionary-developmental origins of multicellularity. American Journal of Botany 101: 6–25. [PubMed: 24363320]
    130.
    Weintraub H. et al. (1991) Muscle-specific transcriptional activation by MyoD. Genes & Development 5: 1377–1386. [PubMed: 1651276]
    131.
    Loewer S. et al. (2010) Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nature Genetics 42: 1113–1117. [PMC free article: PMC3040650] [PubMed: 21057500]
    132.
    Takahashi K. and Yamanaka S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663–676. [PubMed: 16904174]
    133.
    Nakagawa M. et al. (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnology 26: 101–106. [PubMed: 18059259]
    134.
    Zalc A. et al. (2021) Reactivation of the pluripotency program precedes formation of the cranial neural crest. Science 371: eabb4776. [PMC free article: PMC8557957] [PubMed: 33542111]
    135.
    Odom D.T. et al. (2006) Core transcriptional regulatory circuitry in human hepatocytes. Molecular Systems Biology 2: 2006.0017. [PMC free article: PMC1681491] [PubMed: 16738562]
    136.
    Zaret K.S. and Carroll J.S. (2011) Pioneer transcription factors: Establishing competence for gene expression. Genes & Development 25: 2227–2241. [PMC free article: PMC3219227] [PubMed: 22056668]
    137.
    Iwafuchi-Doi M. and Zaret K.S. (2014) Pioneer transcription factors in cell reprogramming. Genes & Development 28: 2679–2692. [PMC free article: PMC4265672] [PubMed: 25512556]
    138.
    Soufi A. et al. (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161: 555–568. [PMC free article: PMC4409934] [PubMed: 25892221]
    139.
    Iwafuchi-Doi M. (2019) The mechanistic basis for chromatin regulation by pioneer transcription factors. WIREs Systems Biology and Medicine 11: e1427. [PMC free article: PMC6585746] [PubMed: 29949240]
    140.
    Whyte W.A. et al. (2013) Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153: 307–319. [PMC free article: PMC3653129] [PubMed: 23582322]
    141.
    Amaral P.P. et al. (2018) Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci. Genome Biology 19: 32. [PMC free article: PMC5853149] [PubMed: 29540241]
    142.
    Winick-Ng W. et al. (2021) Cell-type specialization is encoded by specific chromatin topologies. Nature 599: 684–691. [PMC free article: PMC8612935] [PubMed: 34789882]
    143.
    Claes P. et al. (2018) Genome-wide mapping of global-to-local genetic effects on human facial shape. Nature Genetics 50: 414–423. [PMC free article: PMC5937280] [PubMed: 29459680]
    144.
    Long H.K. et al. (2020) Loss of extreme long-range enhancers in human neural crest drives a craniofacial disorder. Cell Stem Cell 27: 765–783. [PMC free article: PMC7655526] [PubMed: 32991838]
    145.
    White J.D. et al. (2021) Insights into the genetic architecture of the human face. Nature Genetics 53: 45–53. [PMC free article: PMC7796995] [PubMed: 33288918]
    146.
    Naqvi S. et al. (2021) Shared heritability of human face and brain shape. Nature Genetics 53: 830–839. [PMC free article: PMC8232039] [PubMed: 33821002]
    147.
    Liu C. et al. (2021) Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations. PLOS Genetics 17: e1009695. [PMC free article: PMC8375984] [PubMed: 34411106]
    148.
    Fedoroff N.V. (2012) Transposable elements, epigenetics, and genome evolution. Science 338: 758–767. [PubMed: 23145453]
    149.
    Otto S.P. and Whitton J. (2000) Polyploid incidence and evolution. Annual Review of Genetics 34: 401–437. [PubMed: 11092833]
    150.
    Adams K.L. and Wendel J.F. (2005) Polyploidy and genome evolution in plants. Current Opinion in Plant Biology 8: 135–141. [PubMed: 15752992]
    151.
    Bumgarner S.L. et al. (2012) Single-cell analysis reveals that noncoding RNAs contribute to clonal heterogeneity by modulating transcription factor recruitment. Molecular Cell 45: 470–482.
    152.
    van Werven F.J. et al. (2012) Transcription of two long noncoding RNAs mediates mating-type control of gametogenesis in budding yeast. Cell 150: 1170–1181. [PMC free article: PMC3472370] [PubMed: 22959267]
    153.
    Hiriart E. and Verdel A. (2013) Long noncoding RNA-based chromatin control of germ cell differentiation: A yeast perspective. Chromosome Research 21: 653–663. [PMC free article: PMC3857879] [PubMed: 24249577]
    154.
    Moretto F., Wood N.E., Kelly G., Doncic A. and van Werven F.J. (2018) A regulatory circuit of two lncRNAs and a master regulator directs cell fate in yeast. Nature Communications 9: 780. [PMC free article: PMC5823921] [PubMed: 29472539]
    155.
    Moretto F. et al. (2021) Transcription levels of a noncoding RNA orchestrate opposing regulatory and cell fate outcomes in yeast. Cell Reports 34: 108643. [PMC free article: PMC7816125] [PubMed: 33472063]
    156.
    Chacko N. et al. (2015) The lncRNA RZE1 controls cryptococcal morphological transition. PLOS Genetics 11: e1005692. [PMC free article: PMC4654512] [PubMed: 26588844]
    157.
    Kim W., Miguel-Rojas C., Wang J., Townsend J.P. and Trail F. (2018) Developmental dynamics of long noncoding RNA expression during sexual fruiting body formation in Fusarium graminearum. mBio 9: e01292. [PMC free article: PMC6094484] [PubMed: 30108170]
    158.
    Avesson L. et al. (2011) Abundant class of non-coding RNA regulates development in the social amoeba Dictyostelium discoideum. RNA Biology 8: 1094–1104. [PubMed: 21941123]
    159.
    Kjellin J. et al. (2021) Abundantly expressed class of noncoding RNAs conserved through the multicellular evolution of dictyostelid social amoebas. Genome Research 31: 436–447. [PMC free article: PMC7919456] [PubMed: 33479022]
    160.
    Nowacki M. et al. (2007) RNA-mediated epigenetic programming of a genome-rearrangement pathway. Nature 451: 153–158. [PMC free article: PMC2647009] [PubMed: 18046331]
    161.
    Lindblad K.A., Bracht J.R., Williams A.E. and Landweber L.F. (2017) Thousands of RNA-cached copies of whole chromosomes are present in the ciliate Oxytricha during development. RNA 23: 1200–1208. [PMC free article: PMC5513065] [PubMed: 28450531]
    162.
    Allen S.E. and Nowacki M. (2020) Roles of noncoding RNAs in ciliate genome architecture. Journal of Molecular Biology 432: 4186–4198. [PMC free article: PMC7374600] [PubMed: 31926952]
    163.
    Barcons-Simon A., Cordon-Obras C., Guizetti J., Bryant J.M. and Scherf A. (2020) CRISPR interference of a clonally variant GC-rich noncoding RNA family leads to general repression of var genes in Plasmodium falciparum. mBio 11: e03054–19. [PMC free article: PMC6974570] [PubMed: 31964736]
    164.
    van Noort V. and Huynen M.A. (2006) Combinatorial gene regulation in Plasmodium falciparum. Trends in Genetics 22: 73–78. [PubMed: 16380193]
    165.
    Sebé-Pedrós A. et al. (2016) The dynamic regulatory genome of Capsaspora and the origin of animal multicellularity. Cell 165: 1224–1237. [PMC free article: PMC4877666] [PubMed: 27114036]
    166.
    Schwaiger M. et al. (2014) Evolutionary conservation of the eumetazoan gene regulatory landscape. Genome Research 24: 639–650. [PMC free article: PMC3975063] [PubMed: 24642862]
    167.
    Gaiti F. et al. (2017) Landscape of histone modifications in a sponge reveals the origin of animal cis-regulatory complexity. eLife 6: e22194. [PMC free article: PMC5429095] [PubMed: 28395144]
    168.
    Wong E.S. et al. (2020) Deep conservation of the enhancer regulatory code in animals. Science 370: eaax8137. [PubMed: 33154111]
    169.
    Olsen P.H. and Ambros V. (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology 216: 671–680. [PubMed: 10642801]
    170.
    Reinhart B.J. et al. (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403: 901–906. [PubMed: 10706289]
    171.
    Slack F.J. et al. (2000) The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Molecular Cell 5: 659–669. [PubMed: 10882102]
    172.
    Abbott A.L. et al. (2005) The let-7 microRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Developmental Cell 9: 403–414. [PMC free article: PMC3969732] [PubMed: 16139228]
    173.
    Tsialikas J., Romens M.A., Abbott A. and Moss E.G. (2017) Stage-specific timing of the microRNA regulation of lin-28 by the heterochronic gene lin-14 in Caenorhabditis elegans. Genetics 205: 251–262. [PMC free article: PMC5223506] [PubMed: 27815363]
    174.
    Lawson H.N., Wexler L.R., Wnuk H.K. and Portman D.S. (2020) Dynamic, non-binary specification of sexual state in the C. elegans nervous system. Current Biology 30: 3617–3623. [PMC free article: PMC7511423] [PubMed: 32707065]
    175.
    Jukam D., Shariati S.A.M. and Skotheim J.M. (2017) Zygotic genome activation in vertebrates. Developmental Cell 42: 316–332. [PMC free article: PMC5714289] [PubMed: 28829942]
    176.
    Vastenhouw N.L., Cao W.X. and Lipshitz H.D. (2019) The maternal-to-zygotic transition revisited. Development 146: dev161471. [PubMed: 31189646]
    177.
    Cuykendall T.N. and Houston D.W. (2010) Identification of germ plasm-associated transcripts by microarray analysis of Xenopus vegetal cortex RNA. Developmental Dynamics 239: 1838–1848. [PMC free article: PMC3065113] [PubMed: 20503379]
    178.
    D’Orazio F.M. et al. (2021) Germ cell differentiation requires Tdrd7-dependent chromatin and transcriptome reprogramming marked by germ plasm relocalization. Developmental Cell 56: 641–656. [PMC free article: PMC7957325] [PubMed: 33651978]
    179.
    Sharma U. (2019) Paternal contributions to offspring health: Role of sperm small RNAs in intergenerational transmission of epigenetic information. Frontiers in Cell and Developmental Biology 7: 215. [PMC free article: PMC6803970] [PubMed: 31681757]
    180.
    Zhang Y., Shi J., Rassoulzadegan M., Tuorto F. and Chen Q. (2019) Sperm RNA code programmes the metabolic health of offspring. Nature Reviews Endocrinology 15: 489–498. [PMC free article: PMC6626572] [PubMed: 31235802]
    181.
    Piasecka B., Lichocki P., Moretti S., Bergmann S. and Robinson-Rechavi M. (2013) The hourglass and the early conservation models—co-existing patterns of developmental constraints in vertebrates. PLOS Genetics 9: e1003476. [PMC free article: PMC3636041] [PubMed: 23637639]
    182.
    Irie N. and Kuratani S. (2014) The developmental hourglass model: A predictor of the basic body plan? Development 141: 4649–4655. [PubMed: 25468934]
    183.
    Atallah J. and Lott S.E. (2018) Evolution of maternal and zygotic mRNA complements in the early Drosophila embryo. PLOS Genetics 14: e1007838. [PMC free article: PMC6312346] [PubMed: 30557299]
    184.
    Kalinka A.T. et al. (2010) Gene expression divergence recapitulates the developmental hourglass model. Nature 468: 811–814. [PubMed: 21150996]
    185.
    Ninova M., Ronshaugen M. and Griffiths-Jones S. (2014) Conserved temporal patterns of microRNA expression in Drosophila support a developmental hourglass model. Genome Biology and Evolution 6: 2459–2467. [PMC free article: PMC4202322] [PubMed: 25169982]
    186.
    Kauffman S. (1969) Homeostasis and differentiation in random genetic control networks. Nature 224: 177–178. [PubMed: 5343519]
    187.
    Glass L. and Kauffman S.A. (1973) The logical analysis of continuous, non-linear biochemical control networks. Journal of Theoretical Biology 39: 103–129. [PubMed: 4741704]
    188.
    Kauffman S. (1974) The large scale structure and dynamics of gene control circuits: An ensemble approach. Journal of Theoretical Biology 44: 167–190. [PubMed: 4595774]
    189.
    Kauffman S. (2003) Understanding genetic regulatory networks. International Journal of Astrobiology 2: 131–139.
    190.
    Kauffman S. (2004) A proposal for using the ensemble approach to understand genetic regulatory networks. Journal of Theoretical Biology 230: 581–590. [PubMed: 15363677]
    191.
    Reményi A., Schöler H.R. and Wilmanns M. (2004) Combinatorial control of gene expression. Nature Structural & Molecular Biology 11: 812–815. [PubMed: 15332082]
    192.
    Levine M. and Davidson E.H. (2005) Gene regulatory networks for development. Proceedings of the National Academy of Sciences USA 102: 4936–4942. [PMC free article: PMC555974] [PubMed: 15788537]
    193.
    Yuh C.H., Bolouri H. and Davidson E.H. (1998) Genomic cis-regulatory logic: Experimental and computational analysis of a sea urchin gene. Science 279: 1896–902. [PubMed: 9506933]
    194.
    Howard M.L. and Davidson E.H. (2004) cis-Regulatory control circuits in development. Developmental Biology 271: 109–118. [PubMed: 15196954]
    195.
    Davidson E.H. and Erwin D.H. (2006) Gene regulatory networks and the evolution of animal body plans. Science 311: 796–800. [PubMed: 16469913]
    196.
    Peter I.S. and Davidson E.H. (2011) Evolution of gene regulatory networks controlling body plan development. Cell 144: 970–985. [PMC free article: PMC3076009] [PubMed: 21414487]
    197.
    Albert R. and Othmer H.G. (2003) The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster. Journal of Theoretical Biology 223: 1–18. [PMC free article: PMC6388622] [PubMed: 12782112]
    198.
    Espinosa-Soto C., Padilla-Longoria P. and Alvarez-Buylla E.R. (2004) A gene regulatory network model for cell-fate determination during Arabidopsis thaliana flower development that is robust and recovers experimental gene expression profiles. Plant Cell 16: 2923. [PMC free article: PMC527189] [PubMed: 15486106]
    199.
    Li F., Long T., Lu Y., Ouyang Q. and Tang C. (2004) The yeast cell-cycle network is robustly designed. Proceedings of the National Academy of Sciences USA 101: 4781–4786. [PMC free article: PMC387325] [PubMed: 15037758]
    200.
    Bornholdt S. (2008) Boolean network models of cellular regulation: Prospects and limitations. Journal of The Royal Society Interface 5: S85–94. [PMC free article: PMC2386560] [PubMed: 18508746]
    201.
    Payankaulam S., Li L.M. and Arnosti D.N. (2010) Transcriptional repression: Conserved and evolved features. Current Biology 20: R764–71. [PMC free article: PMC3033598] [PubMed: 20833321]
    202.
    Bintu L. et al. (2005) Transcriptional regulation by the numbers: Models. Current Opinion in Genetics and Development 15: 116–124. [PMC free article: PMC3482385] [PubMed: 15797194]
    203.
    van Hijum S.A.F.T., Medema M.H. and Kuipers O.P. (2009) Mechanisms and evolution of control logic in prokaryotic transcriptional regulation. Microbiology and Molecular Biology Reviews 73: 481–509. [PMC free article: PMC2738135] [PubMed: 19721087]
    204.
    Ferraris L. et al. (2011) Combinatorial binding of transcription factors in the pluripotency control regions of the genome. Genome Research 21: 1055–1064. [PMC free article: PMC3129248] [PubMed: 21527551]
    205.
    Luna-Zurita L. et al. (2016) Complex interdependence regulates heterotypic transcription factor distribution and coordinates cardiogenesis. Cell 164: 999–1014. [PMC free article: PMC4769693] [PubMed: 26875865]
    206.
    Vierstra J. et al. (2020) Global reference mapping of human transcription factor footprints. Nature 583: 729–736. [PMC free article: PMC7410829] [PubMed: 32728250]
    207.
    Moore J.E. et al. (2020) Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583: 699–710. [PMC free article: PMC7410828] [PubMed: 32728249]
    208.
    Thurman R.E. et al. (2012) The accessible chromatin landscape of the human genome. Nature 489: 75–82. [PMC free article: PMC3721348] [PubMed: 22955617]
    209.
    Pliner H.A. et al. (2018) Cicero predicts cis-regulatory DNA interactions from single-cell chromatin accessibility data. Molecular Cell 71: 858–871. [PMC free article: PMC6582963] [PubMed: 30078726]
    210.
    Cusanovich D.A. et al. (2018) A single-cell atlas of in vivo mammalian chromatin accessibility. Cell 174: 1309–1324. [PMC free article: PMC6158300] [PubMed: 30078704]
    211.
    Ptashne M. (1967) Specific binding of the lambda phage repressor to lambda DNA. Nature 214: 232–234. [PubMed: 6034235]
    212.
    Ptashne M. (1988) How eukaryotic transcriptional activators work. Nature 335: 683–689. [PubMed: 3050531]
    213.
    Hasty J., Pradines J., Dolnik M. and Collins J.J. (2000) Noise-based switches and amplifiers for gene expression. Proceedings of the National Academy of Sciences USA 97: 2075–2080. [PMC free article: PMC15756] [PubMed: 10681449]
    214.
    Isaacs F.J., Hasty J., Cantor C.R. and Collins J.J. (2003) Prediction and measurement of an autoregulatory genetic module. Proceedings of the National Academy of Sciences USA 100: 7714–7719. [PMC free article: PMC164653] [PubMed: 12808135]
    215.
    Niklas K.J., Dunker A.K. and Yruela I. (2018) The evolutionary origins of cell type diversification and the role of intrinsically disordered proteins. Journal of Experimental Botany 69: 1437–1446. [PubMed: 29394379]
    216.
    Sigler P.B. (1988) Acid blobs and negative noodles. Nature 333: 210–212. [PubMed: 3367995]
    217.
    Niklas K.J., Bondos S.E., Dunker A.K. and Newman S.A. (2015) Rethinking gene regulatory networks in light of alternative splicing, intrinsically disordered protein domains, and post-translational modifications. Frontiers in Cell and Developmental Biology 3: 8. [PMC free article: PMC4341551] [PubMed: 25767796]
    218.
    Cumberworth A., Lamour G., Babu M.M. and Gsponer J. (2013) Promiscuity as a functional trait: Intrinsically disordered regions as central players of interactomes. Biochemical Journal 454: 361–369. [PubMed: 23988124]
    219.
    Protter D.S.W. et al. (2018) Intrinsically disordered regions can contribute promiscuous interactions to RNP granule assembly. Cell Reports 22: 1401–1412. [PMC free article: PMC5824733] [PubMed: 29425497]
    220.
    Wang J. et al. (2012) Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Research 22: 1798–1812. [PMC free article: PMC3431495] [PubMed: 22955990]
    221.
    Smith C.W. and Valcarcel J. (2000) Alternative pre-mRNA splicing: The logic of combinatorial control. Trends in Biochemical Sciences 25: 381–388. [PubMed: 10916158]
    222.
    Levine M. and Tjian R. (2003) Transcription regulation and animal diversity. Nature 424: 147–151. [PubMed: 12853946]
    223.
    Arnone M.I. and Davidson E.H. (1997) The hardwiring of development: Organization and function of genomic regulatory systems. Development 124: 1851–1864. [PubMed: 9169833]
    224.
    Davidson E.H. (2006) The Regulatory Genome: Gene Regulatory Networks In Development And Evolution (Academic Press, New York).
    225.
    Carroll S.B. (2008) Evo-devo and an expanding evolutionary synthesis: A genetic theory of morphological evolution. Cell 134: 25–36. [PubMed: 18614008]
    226.
    Peter I.S. and Davidson E.H. (2011) A gene regulatory network controlling the embryonic specification of endoderm. Nature 474: 635–639. [PMC free article: PMC3976212] [PubMed: 21623371]
    227.
    Bhattacharjee S., Renganaath K., Mehrotra R. and Mehrotra S. (2013) Combinatorial control of gene expression. BioMed Research International 2013: 407263. [PMC free article: PMC3771257] [PubMed: 24069600]
    228.
    Peter I.S. and Davidson E.H. (2016) Implications of developmental gene regulatory networks inside and outside developmental biology. Current Topics in Developmental Biology 117: 237–251. [PubMed: 26969981]
    229.
    Scholes C., DePace A.H. and Sánchez Á. (2017) Combinatorial gene regulation through kinetic control of the transcription cycle. Cell Systems 4: 97–108. [PMC free article: PMC5469051] [PubMed: 28041762]
    230.
    Peter I.S. and Davidson E.H. (2017) Assessing regulatory information in developmental gene regulatory networks. Proceedings of the National Academy of Sciences USA 114: 5862–5869. [PMC free article: PMC5468647] [PubMed: 28584110]
    231.
    Azpeitia E. et al. (2017) The combination of the functionalities of feedback circuits is determinant for the attractors’ number and size in pathway-like Boolean networks. Scientific Reports 7: 42023. [PMC free article: PMC5301197] [PubMed: 28186191]
    232.
    Kauffman S.A. (1969) Metabolic stability and epigenesis in randomly constructed genetic nets. Journal of Theoretical Biology 22: 437–467. [PubMed: 5803332]
    233.
    Samuelsson B. and Troein C. (2003) Superpolynomial growth in the number of attractors in Kauffman networks. Physical Review Letters 90: 098701. [PubMed: 12689263]
    234.
    Buchler N.E., Gerland U. and Hwa T. (2003) On schemes of combinatorial transcription logic. Proceedings of the National Academy of Sciences USA 100: 5136–5141. [PMC free article: PMC404558] [PubMed: 12702751]
    235.
    Akhlaghpour H. (2022) An RNA-based theory of natural universal computation. Journal of Theoretical Biology 536: 110984. [PubMed: 34979104]
    236.
    Eddington A.S. (1956) The constants of nature, in J.R. Newman (ed.) The World of Mathematics 2 (Simon & Schuster, New York).
    237.
    Stampfel G. et al. (2015) Transcriptional regulators form diverse groups with context-dependent regulatory functions. Nature 528: 147–151. [PubMed: 26550828]
    238.
    Jolma A. et al. (2015) DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature 527: 384–388. [PubMed: 26550823]
    239.
    Chovanec P. et al. (2021) Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states. Nature Communications 12: 2098. [PMC free article: PMC8026613] [PubMed: 33828098]
    240.
    Bright A.R. et al. (2021) Combinatorial transcription factor activities on open chromatin induce embryonic heterogeneity in vertebrates. EMBO Journal 40: e104913. [PMC free article: PMC8090851] [PubMed: 33555045]
    241.
    Thomas H.F. et al. (2021) Temporal dissection of an enhancer cluster reveals distinct temporal and functional contributions of individual elements. Molecular Cell 81: 969–982. [PubMed: 33482114]
    242.
    Soldatov R. et al. (2019) Spatiotemporal structure of cell fate decisions in murine neural crest. Science 364: eaas9536. [PubMed: 31171666]
    243.
    Croft L.J., Lercher M.J., Gagen M.J. and Mattick J.S. (2003) Is prokaryotic complexity limited by accelerated growth in regulatory overhead? Genome Biology Preprint Depository http:​//genomebiology.com/qc/2003/5/1/p2.
    244.
    van Nimwegen E. (2003) Scaling laws in the functional content of genomes. Trends in Genetics 19: 479–484. [PubMed: 12957540]
    245.
    Mattick J.S. and Gagen M.J. (2005) Accelerating networks. Science 307: 856–858. [PubMed: 15705831]
    246.
    Molina N. and van Nimwegen E. (2008) Universal patterns of purifying selection at noncoding positions in bacteria. Genome Research 18: 148–160. [PMC free article: PMC2134783] [PubMed: 18032729]
    247.
    Charoensawan V., Wilson D. and Teichmann S.A. (2010) Genomic repertoires of DNA-binding transcription factors across the tree of life. Nucleic Acids Research 38: 7364–7377. [PMC free article: PMC2995046] [PubMed: 20675356]
    248.
    Gagen M.J. and Mattick J.S. (2005) Inherent size constraints on prokaryote gene networks due to “accelerating” growth. Theory in Bioscience 123: 381–411. [PubMed: 18202872]
    249.
    Mattick J.S. (2011) The central role of RNA in human development and cognition. FEBS Letters 585: 1600–1616. [PubMed: 21557942]
    250.
    Liu G., Mattick J.S. and Taft R.J. (2013) A meta-analysis of the genomic and transcriptomic composition of complex life. Cell Cycle 12: 2061–2072. [PMC free article: PMC3737309] [PubMed: 23759593]
    251.
    Kapusta A. and Feschotte C. (2014) Volatile evolution of long noncoding RNA repertoires: Mechanisms and biological implications. Trends in Genetics 30: 439–452. [PMC free article: PMC4464757] [PubMed: 25218058]
    252.
    Alberti C. and Cochella L. (2017) A framework for understanding the roles of miRNAs in animal development. Development 144: 2548–2559. [PubMed: 28720652]

    Chapter 16

    1.
    Paul J. and Duerksen J.D. (1975) Chromatin-associated RNA content of heterochromatin and euchromatin. Molecular and Cellular Biochemistry 9: 9–16. [PubMed: 1186664]
    2.
    Pederson T. and Bhorjee J.S. (1979) Evidence for a role of RNA in eukaryotic chromosome structure. Metabolically stable, small nuclear RNA species are covalently linked to chromosomal DNA in HeLa cells. Journal of Molecular Biology 128: 451–480. [PubMed: 571474]
    3.
    Bynum J.W. and Volkin E. (1980) Chromatin-associated RNA: Differential extraction and characterization. Biochimica et Biophysica Acta 607: 304–318. [PubMed: 7370269]
    4.
    Nickerson J.A., Krochmalnic G., Wan K.M. and Penman S. (1989) Chromatin architecture and nuclear RNA. Proceedings of the National Academy of Sciences USA 86: 177–181. [PMC free article: PMC286427] [PubMed: 2911567]
    5.
    Bernstein E. and Allis C.D. (2005) RNA meets chromatin. Genes & Development 19: 1635–1655. [PubMed: 16024654]
    6.
    Chakalova L., Debrand E., Mitchell J.A., Osborne C.S. and Fraser P. (2005) Replication and transcription: Shaping the landscape of the genome. Nature Reviews Genetics 6: 669–677. [PubMed: 16094312]
    7.
    Rodriguez-Campos A. and Azorin F. (2007) RNA Is an integral component of chromatin that contributes to its structural organization. PLOS ONE 2: e1182. [PMC free article: PMC2063516] [PubMed: 18000552]
    8.
    Mondal T., Rasmussen M., Pandey G.K., Isaksson A. and Kanduri C. (2010) Characterization of the RNA content of chromatin. Genome Research 20: 899–907. [PMC free article: PMC2892091] [PubMed: 20404130]
    9.
    Schubert T. et al. (2012) Df31 protein and snoRNAs maintain accessible higher-order structures of chromatin. Molecular Cell 48: 434–444. [PubMed: 23022379]
    10.
    Rinn J. and Guttman M. (2014) RNA and dynamic nuclear organization. Science 345: 1240–1241. [PMC free article: PMC4186717] [PubMed: 25214588]
    11.
    Sridhar B. et al. (2017) Systematic mapping of RNA-chromatin interactions in vivo. Current Biology 27: 602–609. [PMC free article: PMC5319903] [PubMed: 28132817]
    12.
    Li X. et al. (2017) GRID-seq reveals the global RNA–chromatin interactome. Nature Biotechnology 35: 940–950. [PMC free article: PMC5953555] [PubMed: 28922346]
    13.
    Bell J.C. et al. (2018) Chromatin-associated RNA sequencing (ChAR-seq) maps genome-wide RNA-to-DNA contacts. eLife 7: e27024. [PMC free article: PMC5962340] [PubMed: 29648534]
    14.
    Subhash S. et al. (2018) H3K4me2 and WDR5 enriched chromatin interacting long non-coding RNAs maintain transcriptionally competent chromatin at divergent transcriptional units. Nucleic Acids Research 46: 9384–9400. [PMC free article: PMC6182144] [PubMed: 30010961]
    15.
    Schwartz U. et al. (2019) Characterizing the nuclease accessibility of DNA in human cells to map higher order structures of chromatin. Nucleic Acids Research 47: 1239–1254. [PMC free article: PMC6379673] [PubMed: 30496478]
    16.
    Li X. and Fu X.-D. (2019) Chromatin-associated RNAs as facilitators of functional genomic interactions. Nature Reviews Genetics 20: 503–519. [PMC free article: PMC7684979] [PubMed: 31160792]
    17.
    Mishra K. and Kanduri C. (2019) Understanding long noncoding RNA and chromatin interactions: What we know so far. Noncoding RNA 5: 54. [PMC free article: PMC6958424] [PubMed: 31817041]
    18.
    Thakur J. and Henikoff S. (2020) Architectural RNA in chromatin organization. Biochemical Society Transactions 48: 1967–1978. [PMC free article: PMC7609026] [PubMed: 32897323]
    19.
    Chu C., Qu K., Zhong F.L., Artandi S.E. and Chang H.Y. (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Molecular Cell 44: 667–678. [PMC free article: PMC3249421] [PubMed: 21963238]
    20.
    Werner M.S. and Ruthenburg A.J. (2015) Nuclear fractionation reveals thousands of chromatin-tethered noncoding rnas adjacent to active genes. Cell Reports 12: 1089–1098. [PMC free article: PMC5697714] [PubMed: 26257179]
    21.
    Werner M.S. et al. (2017) Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription. Nature Structural & Molecular Biology 24: 596–603. [PMC free article: PMC5682930] [PubMed: 28628087]
    22.
    Li Z. et al. (2015) Exon-intron circular RNAs regulate transcription in the nucleus. Nature Structural & Molecular Biology 22: 256–264. [PubMed: 25664725]
    23.
    Conn V.M. et al. (2017) A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation. Nature Plants 3: 17053. [PubMed: 28418376]
    24.
    Studniarek C., Egloff S. and Murphy S. (2021) Noncoding RNAs set the stage for RNA polymerase II transcription. Trends in Genetics 37: 279–291. [PubMed: 33046273]
    25.
    Briese M. and Sendtner M. (2021) Keeping the balance: The noncoding RNA 7SK as a master regulator for neuron development and function. Bioessays 43: e2100092. [PubMed: 34050960]
    26.
    Vilborg A., Passarelli M.C., Yario T.A., Tycowski K.T. and Steitz J.A. (2015) Widespread inducible transcription downstream of human genes. Molecular Cell 59: 449–461. [PMC free article: PMC4530028] [PubMed: 26190259]
    27.
    Shevtsov S.P. and Dundr M. (2011) Nucleation of nuclear bodies by RNA. Nature Cell Biology 13: 167–173. [PubMed: 21240286]
    28.
    Sharma P. and Beato M. (2018) Long non-coding RNAs are driver to maintain the chromatin active regions at divergent transcriptional units. Non-coding RNA Investigation 2: 50.
    29.
    Xiao R. et al. (2019) Pervasive chromatin-RNA binding protein interactions enable RNA-based regulation of transcription. Cell 178: 107–121. [PMC free article: PMC6760001] [PubMed: 31251911]
    30.
    Trigiante G., Blanes Ruiz N. and Cerase A. (2021) Emerging roles of repetitive and repeat-containing RNA in nuclear and chromatin organization and gene expression. Frontiers in Cell and Developmental Biology 9: 2730. [PMC free article: PMC8552494] [PubMed: 34722514]
    31.
    Hall L.L. et al. (2014) Stable C0T-1 repeat RNA Is abundant and is associated with euchromatic interphase chromosomes. Cell 156: 907–919. [PMC free article: PMC4023122] [PubMed: 24581492]
    32.
    Lu J.Y. et al. (2021) Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome. Cell Research 31: 613–630. [PMC free article: PMC8169921] [PubMed: 33514913]
    33.
    Fadloun A. et al. (2013) Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA. Nature Structural & Molecular Biology 20: 332–338. [PubMed: 23353788]
    34.
    Percharde M. et al. (2018) A LINE1-nucleolin partnership regulates early development and ESC identity. Cell 174: 391–405. [PMC free article: PMC6046266] [PubMed: 29937225]
    35.
    Ballarino M. et al. (2018) Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice. EMBO Journal 37: e99697. [PMC free article: PMC6138438] [PubMed: 30177572]
    36.
    Abdalla M.O.A. et al. (2019) The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis. Nature Communications 10: 3778. [PMC free article: PMC6706407] [PubMed: 31439835]
    37.
    Oh H.J. et al. (2021) Jpx RNA regulates CTCF anchor site selection and formation of chromosome loops. Cell 184: P6157–73. [PMC free article: PMC8671370] [PubMed: 34856126]
    38.
    Li L. et al. (2021) Global profiling of RNA–chromatin interactions reveals co-regulatory gene expression networks in Arabidopsis. Nature Plants 7: 1364–1378. [PubMed: 34650265]
    39.
    Lei E.P. and Corces V.G. (2006) RNA interference machinery influences the nuclear organization of a chromatin insulator. Nature Genetics 38: 936–941. [PubMed: 16862159]
    40.
    Shuaib M. et al. (2019) Nuclear AGO1 regulates gene expression by affecting chromatin architecture in human cells. Cell Systems 9: 446–458. [PubMed: 31629687]
    41.
    Kim S., Yu N.-K. and Kaang B.-K. (2015) CTCF as a multifunctional protein in genome regulation and gene expression. Experimental & Molecular Medicine 47: e166. [PMC free article: PMC4491725] [PubMed: 26045254]
    42.
    Diehl A.G., Ouyang N. and Boyle A.P. (2020) Transposable elements contribute to cell and species-specific chromatin looping and gene regulation in mammalian genomes. Nature Communications 11: 1796. [PMC free article: PMC7156512] [PubMed: 32286261]
    43.
    Zhang Y. et al. (2019) Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. Nature Genetics 51: 1380–1388. [PMC free article: PMC6722002] [PubMed: 31427791]
    44.
    Lai F. et al. (2013) Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature 494: 497–501. [PMC free article: PMC4109059] [PubMed: 23417068]
    45.
    Luo S. et al. (2016) Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell 18: 637–652. [PubMed: 26996597]
    46.
    Chueh A.C., Northrop E.L., Brettingham-Moore K.H., Choo K.H. and Wong L.H. (2009) LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin. PLOS Genetics 5: e1000354. [PMC free article: PMC2625447] [PubMed: 19180186]
    47.
    Du Y., Topp C.N. and Dawe R.K. (2010) DNA binding of centromere protein C (CENPC) Is stabilized by single-stranded RNA. PLOS Genetics 6: e1000835. [PMC free article: PMC2816676] [PubMed: 20140237]
    48.
    Rošić S., Köhler F. and Erhardt S. (2014) Repetitive centromeric satellite RNA is essential for kinetochore formation and cell division. Journal of Cell Biology 207: 335–349. [PMC free article: PMC4226727] [PubMed: 25365994]
    49.
    Corless S., Höcker S. and Erhardt S. (2020) Centromeric RNA and its function at and beyond centromeric chromatin. Journal of Molecular Biology 432: 4257–4269. [PubMed: 32247764]
    50.
    Bierhoff H., Postepska-Igielska A. and Grummt I. (2014) Noisy silence: Non-coding RNA and heterochromatin formation at repetitive elements. Epigenetics 9: 53–61. [PMC free article: PMC3928186] [PubMed: 24121539]
    51.
    Hall I.M., Noma K. and Grewal S.I. (2003) RNA interference machinery regulates chromosome dynamics during mitosis and meiosis in fission yeast. Proceedings of the National Academy of Sciences USA 100: 193–198. [PMC free article: PMC140924] [PubMed: 12509501]
    52.
    Pal-Bhadra M. et al. (2004) Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303: 669–672. [PubMed: 14752161]
    53.
    Fukagawa T. et al. (2004) Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nature Cell Biology 6: 784–791. [PubMed: 15247924]
    54.
    Zofall M. and Grewal S.I. (2006) RNAi-mediated heterochromatin assembly in fission yeast. Cold Spring Harbor Symposia on Quantitative Biology 71: 487–496. [PubMed: 17381331]
    55.
    Brower-Toland B. et al. (2007) Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes & Development 21: 2300–2311. [PMC free article: PMC1973144] [PubMed: 17875665]
    56.
    Muchardt C. et al. (2002) Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1. EMBO Reports 3: 975–981. [PMC free article: PMC1307621] [PubMed: 12231507]
    57.
    Maison C. et al. (2002) Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nature Genetics 30: 329–334. [PubMed: 11850619]
    58.
    Camacho O.V. et al. (2017) Major satellite repeat RNA stabilize heterochromatin retention of Suv39h enzymes by RNA-nucleosome association and RNA:DNA hybrid formation. eLife 6: e25293. [PMC free article: PMC5538826] [PubMed: 28760199]
    59.
    Johnson W.L. et al. (2017) RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin. eLife 6: e25299. [PMC free article: PMC5538822] [PubMed: 28760200]
    60.
    Bierhoff H. et al. (2014) Quiescence-induced lncRNAs trigger H4K20 trimethylation and transcriptional silencing. Molecular Cell 54: 675–682. [PubMed: 24768537]
    61.
    Azzalin C.M., Reichenbach P., Khoriauli L., Giulotto E. and Lingner J. (2007) Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318: 798–801. [PubMed: 17916692]
    62.
    Montero J.J. et al. (2018) TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin. Nature Communications 9: 1548. [PMC free article: PMC5906467] [PubMed: 29670078]
    63.
    Ding D.Q. et al. (2012) Meiosis-specific noncoding RNA mediates robust pairing of homologous chromosomes in meiosis. Science 336: 732–736. [PubMed: 22582262]
    64.
    Ding D.-Q. et al. (2019) Chromosome-associated RNA–protein complexes promote pairing of homologous chromosomes during Cmeiosis in Schizosaccharomyces pombe. Nature Communications 10: 5598. [PMC free article: PMC6898681] [PubMed: 31811152]
    65.
    Hendrickson D.G., Kelley D.R., Tenen D., Bernstein B. and Rinn J.L. (2016) Widespread RNA binding by chromatin-associated proteins. Genome Biology 17: 28. [PMC free article: PMC4756407] [PubMed: 26883116]
    66.
    Guo F., Li L., Yang W., Hu J.-F. and Cui J. (2021) Long noncoding RNA: A resident staff of genomic instability regulation in tumorigenesis. Cancer Letters 503: 103–109. [PubMed: 33516792]
    67.
    Zaret K.S. and Carroll J.S. (2011) Pioneer transcription factors: Establishing competence for gene expression. Genes & Development 25: 2227–2241. [PMC free article: PMC3219227] [PubMed: 22056668]
    68.
    Iwafuchi-Doi M. and Zaret K.S. (2014) Pioneer transcription factors in cell reprogramming. Genes & Development 28: 2679–2692. [PMC free article: PMC4265672] [PubMed: 25512556]
    69.
    Soufi A. et al. (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161: 555–568. [PMC free article: PMC4409934] [PubMed: 25892221]
    70.
    Mayran A. and Drouin J. (2018) Pioneer transcription factors shape the epigenetic landscape. Journal of Biological Chemistry 293: 13795–13804. [PMC free article: PMC6130937] [PubMed: 29507097]
    71.
    Iwafuchi-Doi M. (2019) The mechanistic basis for chromatin regulation by pioneer transcription factors. WIREs Systems Biology and Medicine 11: e1427. [PMC free article: PMC6585746] [PubMed: 29949240]
    72.
    Takahashi K. and Yamanaka S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663–676. [PubMed: 16904174]
    73.
    Loh Y.H. et al. (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genetics 38: 431–440. [PubMed: 16518401]
    74.
    Masui S. et al. (2007) Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nature Cell Biology 9: 625–635. [PubMed: 17515932]
    75.
    Yu J. et al. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318: 1917–1920. [PubMed: 18029452]
    76.
    Zalc A. et al. (2021) Reactivation of the pluripotency program precedes formation of the cranial neural crest. Science 371: eabb4776. [PMC free article: PMC8557957] [PubMed: 33542111]
    77.
    Wang Z., Oron E., Nelson B., Razis S. and Ivanova N. (2012) Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells. Cell Stem Cell 10: 440–454. [PubMed: 22482508]
    78.
    Dunwell T.L. and Holland P.W.H. (2017) A sister of NANOG regulates genes expressed in pre-implantation human development. Open Biology 7: 170027. [PMC free article: PMC5413911] [PubMed: 28446706]
    79.
    Catron K.M., Iler N. and Abate C. (1993) Nucleotides flanking a conserved TAAT core dictate the DNA binding specificity of three murine homeodomain proteins. Molecular and Cellular Biology 13: 2354–2365. [PMC free article: PMC359556] [PubMed: 8096059]
    80.
    Bürglin T.R. and Affolter M. (2016) Homeodomain proteins: An update. Chromosoma 125: 497–521. [PMC free article: PMC4901127] [PubMed: 26464018]
    81.
    Jauch R., Ng C.K.L., Saikatendu K.S., Stevens R.C. and Kolatkar P.R. (2008) Crystal structure and DNA binding of the homeodomain of the stem cell transcription factor Nanog. Journal of Molecular Biology 376: 758–770. [PubMed: 18177668]
    82.
    Fang X. et al. (2011) Genome-wide analysis of OCT4 binding sites in glioblastoma cancer cells. Journal of Zhejiang University. Science B 12: 812–819. [PMC free article: PMC3190096] [PubMed: 21960344]
    83.
    Ferraris L. et al. (2011) Combinatorial binding of transcription factors in the pluripotency control regions of the genome. Genome Research 21: 1055–1064. [PMC free article: PMC3129248] [PubMed: 21527551]
    84.
    Tantin D. (2013) Oct transcription factors in development and stem cells: Insights and mechanisms. Development 140: 2857–2866. [PMC free article: PMC3699277] [PubMed: 23821033]
    85.
    Rodda D.J. et al. (2005) Transcriptional regulation of nanog by OCT4 and SOX2. Journal of Biological Chemistry 280: 24731–24737. [PubMed: 15860457]
    86.
    Boyer L.A. et al. (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122: 947–956. [PMC free article: PMC3006442] [PubMed: 16153702]
    87.
    Wang J. et al. (2006) A protein interaction network for pluripotency of embryonic stem cells. Nature 444: 364–368. [PubMed: 17093407]
    88.
    Zhou Q., Chipperfield H., Melton D.A. and Wong W.H. (2007) A gene regulatory network in mouse embryonic stem cells. Proceedings of the National Academy of Sciences USA 104: 16438–16443. [PMC free article: PMC2034259] [PubMed: 17940043]
    89.
    Kashyap V. et al. (2009) Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs. Stem Cells and Development 18: 1093–1108. [PMC free article: PMC3135180] [PubMed: 19480567]
    90.
    Costa Y. et al. (2013) NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 495: 370–374. [PMC free article: PMC3606645] [PubMed: 23395962]
    91.
    Tomita S. et al. (2015) A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation. Nature Communications 6: 6966. [PMC free article: PMC4421845] [PubMed: 25923108]
    92.
    Setten R.L., Chomchan P., Epps E.W., Burnett J.C. and Rossi J.J. (2021) CRED9: A differentially expressed elncRNA regulates expression of transcription factor CEBPA. RNA 27: 891–906. [PMC free article: PMC8284328] [PubMed: 34039742]
    93.
    Lin H., Shabbir A., Molnar M. and Lee T. (2007) Stem cell regulatory function mediated by expression of a novel mouse Oct4 pseudogene. Biochemical and Biophysical Research Communications 355: 111–116. [PubMed: 17280643]
    94.
    Hawkins P.G. and Morris K.V. (2010) Transcriptional regulation of Oct4 by a long non-coding RNA antisense to Oct4-pseudogene 5. Transcription 1: 165–175. [PMC free article: PMC2999937] [PubMed: 21151833]
    95.
    Wang Y. et al. (2013) Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Developmental Cell 25: 69–80. [PubMed: 23541921]
    96.
    Rosa A. and Ballarino M. (2016) Long noncoding RNA regulation of pluripotency. Stem Cells International 2016: 1797692. [PMC free article: PMC4677244] [PubMed: 26697072]
    97.
    Scarola M. et al. (2015) Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA. Nature Communications 6: 7631. [PMC free article: PMC4510692] [PubMed: 26158551]
    98.
    Scarola M. et al. (2020) FUS-dependent loading of SUV39H1 to OCT4 pseudogene-lncRNA programs a silencing complex with OCT4 promoter specificity. Communications Biology 3: 632. [PMC free article: PMC7603346] [PubMed: 33128015]
    99.
    Sheik Mohamed J., Gaughwin P.M., Lim B., Robson P. and Lipovich L. (2010) Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 16: 324–337. [PMC free article: PMC2811662] [PubMed: 20026622]
    100.
    Booth H.A.F. and Holland P.W.H. (2004) Eleven daughters of NANOG. Genomics 84: 229–238. [PubMed: 15233988]
    101.
    Fairbanks D.J. and Maughan P.J. (2006) Evolution of the NANOG pseudogene family in the human and chimpanzee genomes. BMC Evolutionary Biology 6: 12. [PMC free article: PMC1457002] [PubMed: 16469101]
    102.
    Poursani E.M., Mohammad Soltani B. and Mowla S.J. (2016) Differential expression of OCT4 pseudogenes in pluripotent and tumor cell lines. Cell Journal 18: 28–36. [PMC free article: PMC4819383] [PubMed: 27054116]
    103.
    Mehravar M., Ghaemimanesh F. and Poursani E.M. (2021) An overview on the complexity of OCT4: At the level of DNA, RNA and protein. Stem Cell Reviews and Reports 17: 1121–1136. [PubMed: 33389631]
    104.
    Zhang J. et al. (2006) NANOGP8 is a retrogene expressed in cancers. FEBS Journal 273: 1723–1730. [PubMed: 16623708]
    105.
    Svingen T. and Tonissen K.F. (2006) Hox transcription factors and their elusive mammalian gene targets. Heredity 97: 88–96. [PubMed: 16721389]
    106.
    Sharov A.A. et al. (2008) Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data. BMC Genomics 9: 269. [PMC free article: PMC2424064] [PubMed: 18522731]
    107.
    Hou L., Srivastava Y. and Jauch R. (2017) Molecular basis for the genome engagement by Sox proteins. Seminars in Cell & Developmental Biology 63: 2–12. [PubMed: 27521520]
    108.
    Li H. et al. (2019) The spatial binding model of the pioneer factor Oct4 with its target genes during cell reprogramming. Computational and Structural Biotechnology Journal 17: 1226–1233. [PMC free article: PMC6944736] [PubMed: 31921389]
    109.
    Luo Z., Rhie S.K. and Farnham P.J. (2019) The enigmatic HOX genes: Can we crack their code? Cancers 11: 323. [PMC free article: PMC6468460] [PubMed: 30866492]
    110.
    Sherwood R.I. et al. (2014) Discovery of directional and nondirectional pioneer transcription factors by modeling DNase profile magnitude and shape. Nature Biotechnology 32: 171–178. [PMC free article: PMC3951735] [PubMed: 24441470]
    111.
    Chovanec P. et al. (2021) Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states. Nature Communications 12: 2098. [PMC free article: PMC8026613] [PubMed: 33828098]
    112.
    Pavlopoulos A. and Akam M. (2011) Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis. Proceedings of the National Academy of Sciences USA 108: 2855–2860. [PMC free article: PMC3041078] [PubMed: 21282633]
    113.
    Dubnau J. and Struhl G. (1996) RNA recognition and translational regulation by a homeodomain protein. Nature 379: 694–699. [PubMed: 8602214]
    114.
    Rivera-Pomar R., Niessing D., Schmidt-Ott U., Gehring W.J. and Jacklë H. (1996) RNA binding and translational suppression by bicoid. Nature 379: 746–749. [PubMed: 8602224]
    115.
    Degani N., Lubelsky Y., Perry R.B.-T., Ainbinder E. and Ulitsky I. (2021) Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage. PLOS Genetics 17: e1009681. [PMC free article: PMC8330917] [PubMed: 34280202]
    116.
    Grosschedl R., Giese K. and Pagel J. (1994) HMG domain proteins: Architectural elements in the assembly of nucleoprotein structures. Trends in Genetics 10: 94–100. [PubMed: 8178371]
    117.
    Hock R., Furusawa T., Ueda T. and Bustin M. (2007) HMG chromosomal proteins in development and disease. Trends in Cell Biology 17: 72–79. [PMC free article: PMC2442274] [PubMed: 17169561]
    118.
    Dodonova S.O., Zhu F., Dienemann C., Taipale J. and Cramer P. (2020) Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function. Nature 580: 669–672. [PubMed: 32350470]
    119.
    Bianchi M.E. and Agresti A. (2005) HMG proteins: Dynamic players in gene regulation and differentiation. Current Opinion in Genetics and Development 15: 496–506. [PubMed: 16102963]
    120.
    Štros M., Launholt D. and Grasser K.D. (2007) The HMG-box: A versatile protein domain occurring in a wide variety of DNA-binding proteins. Cellular and Molecular Life Sciences 64: 2590. [PubMed: 17599239]
    121.
    Holmes Z.E. et al. (2020) The Sox2 transcription factor binds RNA. Nature Communications 11: 1805. [PMC free article: PMC7156710] [PubMed: 32286318]
    122.
    Cajigas I. et al. (2021) Sox2-Evf2 lncRNA mechanisms of chromosome topological control in developing forebrain. Development 148: dev197202. [PMC free article: PMC7990859] [PubMed: 33593819]
    123.
    Genzor P. and Bortvin A. (2015) A unique HMG-box domain of mouse Maelstrom binds structured RNA but not double stranded DNA. PLOS ONE 10: e0120268. [PMC free article: PMC4373776] [PubMed: 25807393]
    124.
    Veretnik S. and Gribskov M. (1999) RNA binding domain of HDV antigen is homologous to the HMG box of SRY. Archives of Virology 144: 1139–1158. [PMC free article: PMC7087091] [PubMed: 10446649]
    125.
    Ng S.-Y., Johnson R. and Stanton L.W. (2012) Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO Journal 31: 522–533. [PMC free article: PMC3273385] [PubMed: 22193719]
    126.
    Ng S.-Y., Bogu G.K., Soh B.S. and Stanton L.W. (2013) The long noncoding RNA RMST interacts with SOX2 to regulate neurogenesis. Molecular Cell 51: 349–359. [PubMed: 23932716]
    127.
    Samudyata et al. (2019) Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells. Experimental Cell Research 381: 129–138. [PMC free article: PMC6994247] [PubMed: 31077711]
    128.
    Hou L. et al. (2020) Concurrent binding to DNA and RNA facilitates the pluripotency reprogramming activity of Sox2. Nucleic Acids Research 48: 3869–3887. [PMC free article: PMC7144947] [PubMed: 32016422]
    129.
    Zhao Z., Dammert M.A., Grummt I. and Bierhoff H. (2016) lncRNA-Induced nucleosome repositioning reinforces transcriptional repression of RNA genes upon hypotonic stress. Cell Reports 14: 1876–1882. [PubMed: 26904956]
    130.
    Wang X., Cairns M.J. and Yan J. (2019) Super-enhancers in transcriptional regulation and genome organization. Nucleic Acids Research 47: 11481–11496. [PMC free article: PMC7145697] [PubMed: 31724731]
    131.
    Kelley D. and Rinn J. (2012) Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biology 13: R107. [PMC free article: PMC3580499] [PubMed: 23181609]
    132.
    Lu X. et al. (2014) The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nature Structural & Molecular Biology 21: 423–425. [PubMed: 24681886]
    133.
    Weintraub H. et al. (1991) Muscle-specific transcriptional activation by MyoD. Genes & Development 5: 1377–1386. [PubMed: 1651276]
    134.
    Caretti G. et al. (2006) The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation. Developmental Cell 11: 547–560. [PubMed: 17011493]
    135.
    Dong A. et al. (2020) A long noncoding RNA, LncMyoD, modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression. Proceedings of the National Academy of Sciences USA 117: 32464–32475. [PMC free article: PMC7768704] [PubMed: 33293420]
    136.
    Yu X. et al. (2017) Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD. Nature Communications 8: 14016. [PMC free article: PMC5241866] [PubMed: 28091529]
    137.
    Pandorf C.E. et al. (2006) Dynamics of myosin heavy chain gene regulation in slow skeletal muscle: Role of natural antisense RNA. Journal of Biological Chemistry 281: 38330–38342. [PubMed: 17030512]
    138.
    Haddad F. et al. (2008) Intergenic transcription and developmental regulation of cardiac myosin heavy chain genes. American Journal of Physiology Heart and Circulation Physiology 294: H29–40. [PubMed: 17982008]
    139.
    Dou M. et al. (2020) The long noncoding RNA MyHC IIA/X-AS contributes to skeletal muscle myogenesis and maintains the fast fiber phenotype. Journal of Biological Chemistry 295: 4937–4949. [PMC free article: PMC7152763] [PubMed: 32152230]
    140.
    Bose D.A. et al. (2017) RNA binding to CBP stimulates histone acetylation and transcription. Cell 168: 135–149. [PMC free article: PMC5325706] [PubMed: 28086087]
    141.
    Becker P.B. and Hörz W. (2002) ATP-dependent nucleosome remodeling. Annual Review of Biochemistry 71: 247–273. [PubMed: 12045097]
    142.
    Clapier C.R., Iwasa J., Cairns B.R. and Peterson C.L. (2017) Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nature Reviews Molecular Cell Biology 18: 407–422. [PMC free article: PMC8127953] [PubMed: 28512350]
    143.
    Prensner J.R. et al. (2013) The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nature Genetics 45: 1392–1398. [PMC free article: PMC3812362] [PubMed: 24076601]
    144.
    Han P. et al. (2014) A long noncoding RNA protects the heart from pathological hypertrophy. Nature 514: 102–106. [PMC free article: PMC4184960] [PubMed: 25119045]
    145.
    Cajigas I. et al. (2015) Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling. Development 142: 2641–2652. [PMC free article: PMC4529037] [PubMed: 26138476]
    146.
    Hu G. et al. (2016) LincRNA-Cox2 promotes late inflammatory gene transcription in macrophages through modulating SWI/SNF-mediated chromatin remodeling. Journal of Immunology 196: 2799–2808. [PMC free article: PMC4779692] [PubMed: 26880762]
    147.
    Atianand M.K. et al. (2016) A long noncoding RNA lincRNA-EPS acts as a transcriptional brake to restrain inflammation. Cell 165: 1672–1685. [PMC free article: PMC5289747] [PubMed: 27315481]
    148.
    Tang Y. et al. (2017) Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer. Molecular Cancer 16: 42. [PMC free article: PMC5316185] [PubMed: 28212646]
    149.
    Liu B. et al. (2017) Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression. Nature Immunology 18: 499–508. [PubMed: 28319097]
    150.
    Leisegang M.S. et al. (2017) Long noncoding RNA MANTIS facilitates endothelial angiogenic function. Circulation 136: 65–79. [PMC free article: PMC5491227] [PubMed: 28351900]
    151.
    Lino Cardenas C.L. et al. (2018) An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm. Nature Communications 9: 1009. [PMC free article: PMC5843596] [PubMed: 29520069]
    152.
    Wang Y. et al. (2018) Long noncoding RNA lncHand2 promotes liver repopulation via c-Met signaling. Journal of Hepatology 69: 861–872. [PubMed: 29653123]
    153.
    Wang Y. et al. (2019) LncRNA HAND2-AS1 promotes liver cancer stem cell self-renewal via BMP signaling. EMBO Journal 38: e101110. [PMC free article: PMC6717889] [PubMed: 31334575]
    154.
    Hu Y.-W. et al. (2019) Long noncoding RNA NEXN-AS1 mitigates atherosclerosis by regulating the actin-binding protein NEXN. Journal of Clinical investigation 129: 1115–1128. [PMC free article: PMC6391138] [PubMed: 30589415]
    155.
    Liu X. et al. (2019) A long noncoding RNA, Antisense IL-7, promotes inflammatory gene transcription through facilitating histone acetylation and switch/sucrose nonfermentable chromatin remodeling. Journal of Immunology 203: 1548–1559. [PubMed: 31383742]
    156.
    Jégu T. et al. (2019) Xist RNA antagonizes the SWI/SNF chromatin remodeler BRG1 on the inactive X chromosome. Nature Structural & Molecular Biology 26: 96–109. [PMC free article: PMC6421574] [PubMed: 30664740]
    157.
    Grossi E. et al. (2020) A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions. Nature Communications 11: 936. [PMC free article: PMC7028943] [PubMed: 32071317]
    158.
    Schutt C. et al. (2020) Linc-MYH configures INO80 to regulate muscle stem cell numbers and skeletal muscle hypertrophy. EMBO Journal 39: e105098. [PMC free article: PMC7667881] [PubMed: 32960481]
    159.
    Patty B.J. and Hainer S.J. (2020) Non-coding RNAs and nucleosome remodeling complexes: An intricate regulatory relationship. Biology 9: 213. [PMC free article: PMC7465399] [PubMed: 32784701]
    160.
    Ducoli L. et al. (2021) LETR1 is a lymphatic endothelial-specific lncRNA governing cell proliferation and migration through KLF4 and SEMA3C. Nature Communications 12: 925. [PMC free article: PMC7876020] [PubMed: 33568674]
    161.
    Santos-Zavaleta A. et al. (2019) RegulonDB v 10.5: Tackling challenges to unify classic and high throughput knowledge of gene regulation in E. coli K-12. Nucleic Acids Research 47: D212–20. [PMC free article: PMC6324031] [PubMed: 30395280]
    162.
    Iuchi S. (2001) Three classes of C2H2 zinc finger proteins. Cellular and Molecular Life Sciences CMLS 58: 625–635. [PubMed: 11361095]
    163.
    Badis G. et al. (2009) Diversity and complexity in DNA recognition by transcription factors. Science 324: 1720–1723. [PMC free article: PMC2905877] [PubMed: 19443739]
    164.
    Mendoza-Vargas A. et al. (2009) Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli. PLOS ONE 4: e7526. [PMC free article: PMC2760140] [PubMed: 19838305]
    165.
    Jolma A. et al. (2013) DNA-binding specificities of human transcription factors. Cell 152: 327–339. [PubMed: 23332764]
    166.
    Castellanos M., Mothi N. and Muñoz V. (2020) Eukaryotic transcription factors can track and control their target genes using DNA antennas. Nature Communications 11: 540. [PMC free article: PMC6987225] [PubMed: 31992709]
    167.
    Negre N. et al. (2011) A cis-regulatory map of the Drosophila genome. Nature 471: 527–531. [PMC free article: PMC3179250] [PubMed: 21430782]
    168.
    Lee B.K. et al. (2012) Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells. Genome Research 22: 9–24. [PMC free article: PMC3246210] [PubMed: 22090374]
    169.
    Wang J. et al. (2012) Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Research 22: 1798–1812. [PMC free article: PMC3431495] [PubMed: 22955990]
    170.
    Kheradpour P. and Kellis M. (2014) Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments. Nucleic Acids Research 42: 2976–2987. [PMC free article: PMC3950668] [PubMed: 24335146]
    171.
    Najafabadi H.S. et al. (2015) C2H2 zinc finger proteins greatly expand the human regulatory lexicon. Nature Biotechnology 33: 555–562. [PubMed: 25690854]
    172.
    Cassiday L.A. and Maher 3rd L.J. (2002) Having it both ways: Transcription factors that bind DNA and RNA. Nucleic Acids Research 30: 4118–4126. [PMC free article: PMC140532] [PubMed: 12364590]
    173.
    Burdach J., O’Connell M.R., Mackay J.P. and Crossley M. (2012) Two-timing zinc finger transcription factors liaising with RNA. Trends in Biochemical Sciences 37: 199–205. [PubMed: 22405571]
    174.
    Pelham H.R. and Brown D.D. (1980) A specific transcription factor that can bind either the 5S RNA gene or 5S RNA. Proceedings of the National Academy of Sciences USA 77: 4170–4174. [PMC free article: PMC349792] [PubMed: 7001457]
    175.
    Honda B.M. and Roeder R.G. (1980) Association of a 5S gene transcription factor with 5S RNA and altered levels of the factor during cell differentiation. Cell 22: 119–126. [PubMed: 6159099]
    176.
    Han H. et al. (2017) Multilayered control of alternative splicing regulatory networks by transcription factors. Molecular Cell 65: 539–553. [PubMed: 28157508]
    177.
    Hastie N.D. (2017) Wilms’ tumour 1 (WT1) in development, homeostasis and disease. Development 144: 2862–2872. [PubMed: 28811308]
    178.
    Larsson S.H. et al. (1995) Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing. Cell 81: 391–401. [PubMed: 7736591]
    179.
    Kennedy D., Ramsdale T., Mattick J. and Little M. (1996) An RNA recognition motif in Wilms’ tumour protein (WT1) revealed by structural modelling. Nature Genetics 12: 329–332. [PubMed: 8589729]
    180.
    Naftelberg S., Schor I.E., Ast G. and Kornblihtt A.R. (2015) Regulation of alternative splicing through coupling with transcription and chromatin structure. Annual Review of Biochemistry 84: 165–198. [PubMed: 26034889]
    181.
    Klamt B. et al. (1998) Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/−KTS splice isoforms. Human Molecular Genetics 7: 709–714. [PubMed: 9499425]
    182.
    Caricasole A. et al. (1996) RNA binding by the Wilms tumor suppressor zinc finger proteins. Proceedings of the National Academy of Sciences USA 93: 7562–7566. [PMC free article: PMC38785] [PubMed: 8755514]
    183.
    Bardeesy N. and Pelletier J. (1998) Overlapping RNA and DNA binding domains of the wt1 tumor suppressor gene product. Nucleic Acids Research 26: 1784–1792. [PMC free article: PMC147468] [PubMed: 9512553]
    184.
    Zhai G., Iskandar M., Barilla K. and Romaniuk P.J. (2001) Characterization of RNA aptamer binding by the Wilms’ tumor suppressor protein WT1. Biochemistry 40: 2032–2040. [PubMed: 11329270]
    185.
    Niksic M., Slight J., Sanford J.R., Caceres J.F. and Hastie N.D. (2004) The Wilms’ tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Human Molecular Genetics 13: 463–471. [PubMed: 14681305]
    186.
    O‘Connor L., Gilmour J. and Bonifer C. (2016) The role of the ubiquitously expressed transcription factor SP1 in tissue-specific transcriptional regulation and in disease. Yale Journal of Biology and Medicine 89: 513–525. [PMC free article: PMC5168829] [PubMed: 28018142]
    187.
    Shi Y. and Berg J.M. (1995) Specific DNA-RNA hybrid binding by zinc finger proteins. Science 268: 282–284. [PubMed: 7536342]
    188.
    Gordon S., Akopyan G., Garban H. and Bonavida B. (2006) Transcription factor YY1: Structure, function, and therapeutic implications in cancer biology. Oncogene 25: 1125–1142. [PubMed: 16314846]
    189.
    Sigova A.A. et al. (2015) Transcription factor trapping by RNA in gene regulatory elements. Science 350: 978–981. [PMC free article: PMC4720525] [PubMed: 26516199]
    190.
    Weintraub A.S. et al. (2017) YY1 is a structural regulator of enhancer-promoter loops. Cell 171: 1573–1588. [PMC free article: PMC5785279] [PubMed: 29224777]
    191.
    Yao H. et al. (2010) Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA. Genes & Development 24: 2543–2555. [PMC free article: PMC2975930] [PubMed: 20966046]
    192.
    Saldana-Meyer R. et al. (2014) CTCF regulates the human p53 gene through direct interaction with its natural antisense transcript, Wrap53. Genes & Development 28: 723–734. [PMC free article: PMC4015496] [PubMed: 24696455]
    193.
    Kung J.T. et al. (2015) Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF. Molecular Cell 57: 361–375. [PMC free article: PMC4316200] [PubMed: 25578877]
    194.
    Hansen A.S. et al. (2019) Distinct classes of chromatin loops revealed by deletion of an RNA-binding region in CTCF. Molecular Cell 76: 395–411. [PMC free article: PMC7251926] [PubMed: 31522987]
    195.
    Kuang S. and Wang L. (2020) Identification and analysis of consensus RNA motifs binding to the genome regulator CTCF. NAR Genomics and Bioinformatics 2: lqaa031. [PMC free article: PMC7671415] [PubMed: 33575587]
    196.
    Wang I.X. et al. (2018) Human proteins that interact with RNA/DNA hybrids. Genome Research 28: 1405–1414. [PMC free article: PMC6120628] [PubMed: 30108179]
    197.
    Abakir A. et al. (2020) N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nature Genetics 52: 48–55. [PMC free article: PMC6974403] [PubMed: 31844323]
    198.
    Crossley M.P., Bocek M. and Cimprich K.A. (2019) R-loops as cellular regulators and genomic threats. Molecular Cell 73: 398–411. [PMC free article: PMC6402819] [PubMed: 30735654]
    199.
    Niehrs C. and Luke B. (2020) Regulatory R-loops as facilitators of gene expression and genome stability. Nature Reviews Molecular Cell Biology 21: 167–178. [PMC free article: PMC7116639] [PubMed: 32005969]
    200.
    Wahba L., Costantino L., Tan F.J., Zimmer A. and Koshland D. (2016) S1-DRIP-seq identifies high expression and polyA tracts as major contributors to R-loop formation. Genes & Development 30: 1327–1338. [PMC free article: PMC4911931] [PubMed: 27298336]
    201.
    Sanz L.A. et al. (2016) Prevalent, dynamic, and conserved R-loop structures associate with specific epigenomic signatures in mammals. Molecular Cell 63: 167–178. [PMC free article: PMC4955522] [PubMed: 27373332]
    202.
    Wickramasinghe V.O. and Venkitaraman A.R. (2016) RNA processing and genome stability: Cause and consequence. Molecular Cell 61: 496–505. [PMC free article: PMC5905668] [PubMed: 26895423]
    203.
    Rinaldi C., Pizzul P., Longhese M.P. and Bonetti D. (2021) Sensing R-loop-associated DNA damage to safeguard genome stability. Frontiers in Cell and Developmental Biology 8: 1657. [PMC free article: PMC7829580] [PubMed: 33505970]
    204.
    Chen P.B., Chen H.V., Acharya D., Rando O.J. and Fazzio T.G. (2015) R loops regulate promoter-proximal chromatin architecture and cellular differentiation. Nature Structural & Molecular Biology 22: 999–1007. [PMC free article: PMC4677832] [PubMed: 26551076]
    205.
    Boque-Sastre R. et al. (2015) Head-to-head antisense transcription and R-loop formation promotes transcriptional activation. Proceedings of the National Academy of Sciences USA 112: 5785–5790. [PMC free article: PMC4426458] [PubMed: 25902512]
    206.
    Nadel J. et al. (2015) RNA:DNA hybrids in the human genome have distinctive nucleotide characteristics, chromatin composition, and transcriptional relationships. Epigenetics & Chromatin 8: 46. [PMC free article: PMC4647656] [PubMed: 26579211]
    207.
    Shiromoto Y., Sakurai M., Minakuchi M., Ariyoshi K. and Nishikura K. (2021) ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells. Nature Communications 12: 1654. [PMC free article: PMC7955049] [PubMed: 33712600]
    208.
    van Holde K. and Zlatanova J. (1994) Unusual DNA structures, chromatin and transcription. BioEssays 16: 59–68. [PubMed: 8141807]
    209.
    Gilbert D.E. and Feigon J. (1999) Multistranded DNA structures. Current Opinion in Structural Biology 9: 305–314. [PubMed: 10361092]
    210.
    Mirkin S.M. (2008) Discovery of alternative DNA structures: A heroic decade (1979–1989). Frontiers in Bioscience 13: 1064–1071. [PubMed: 17981612]
    211.
    Zeraati M. et al. (2018) I-motif DNA structures are formed in the nuclei of human cells. Nature Chemistry 10: 631–637. [PubMed: 29686376]
    212.
    Herbert A. (2019) Z-DNA and Z-RNA in human disease. Communications Biology 2: 7. [PMC free article: PMC6323056] [PubMed: 30729177]
    213.
    Herbert A. (2020) Simple repeats as building blocks for genetic computers. Trends in Genetics 36: 739–750. [PubMed: 32690316]
    214.
    Bekhor I., Bonner J. and Dahmus G.K. (1969) Hybridization of chromosomal RNA to native DNA. Proceedings of the National Academy of Sciences USA 62: 271–277. [PMC free article: PMC285983] [PubMed: 5253662]
    215.
    Lee J.S., Woodsworth M.L., Latimer L.J. and Morgan A.R. (1984) Poly(pyrimidine).poly(purine) synthetic DNAs containing 5-methylcytosine form stable triplexes at neutral pH. Nucleic Acids Research 12: 6603–6614. [PMC free article: PMC320099] [PubMed: 6473110]
    216.
    Goni J.R., de la Cruz X. and Orozco M. (2004) Triplex-forming oligonucleotide target sequences in the human genome. Nucleic Acids Research 32: 354–360. [PMC free article: PMC373298] [PubMed: 14726484]
    217.
    Jalali S., Singh A., Maiti S. and Scaria V. (2017) Genome-wide computational analysis of potential long noncoding RNA mediated DNA:DNA:RNA triplexes in the human genome. Journal of Translational Medicine 15: 186. [PMC free article: PMC7670996] [PubMed: 28865451]
    218.
    Lee J.S., Burkholder G.D., Latimer L.J., Haug B.L. and Braun R.P. (1987) A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes. Nucleic Acids Research 15: 1047–1061. [PMC free article: PMC340507] [PubMed: 2434928]
    219.
    Agazie Y.M., Burkholder G.D. and Lee J.S. (1996) Triplex DNA in the nucleus: Direct binding of triplex-specific antibodies and their effect on transcription, replication and cell growth. Biochemical Journal 316: 461–466. [PMC free article: PMC1217372] [PubMed: 8687388]
    220.
    Ohno M., Fukagawa T., Lee J.S. and Ikemura T. (2002) Triplex-forming DNAs in the human interphase nucleus visualized in situ by polypurine/polypyrimidine DNA probes and antitriplex antibodies. Chromosoma 111: 201–213. [PubMed: 12355210]
    221.
    Cetin N.S. et al. (2019) Isolation and genome-wide characterization of cellular DNA:RNA triplex structures. Nucleic Acids Research 47: 2306–2321. [PMC free article: PMC6411930] [PubMed: 30605520]
    222.
    Farabella I., Di Stefano M., Soler-Vila P., Marti-Marimon M. and Marti-Renom M.A. (2021) Three-dimensional genome organization via triplex-forming RNAs. Nature Structural & Molecular Biology 28: 945–954. [PubMed: 34759378]
    223.
    Soibam B. and Zhamangaraeva A. (2021) LncRNA:DNA triplex-forming sites are positioned at specific areas of genome organization and are predictors for Topologically Associated Domains. BMC Genomics 22: 397. [PMC free article: PMC8164242] [PubMed: 34049493]
    224.
    Vasquez K.M. and Wilson J.H. (1998) Triplex-directed modification of genes and gene activity. Trends in Biochemical Sciences 23: 4–9. [PubMed: 9478127]
    225.
    Carbone G.M., McGuffie E.M., Collier A. and Catapano C.V. (2003) Selective inhibition of transcription of the Ets2 gene in prostate cancer cells by a triplex-forming oligonucleotide. Nucleic Acids Research 31: 833–843. [PMC free article: PMC149218] [PubMed: 12560478]
    226.
    Re R.N., Cook J.L. and Giardina J.F. (2004) The inhibition of tumor growth by triplex-forming oligonucleotides. Cancer Letters 209: 51–53. [PubMed: 15145520]
    227.
    Song J., Intody Z., Li M. and Wilson J.H. (2004) Activation of gene expression by triplex-directed psoralen crosslinks. Gene 324: 183–190. [PubMed: 14693383]
    228.
    Jandura A. and Krause H.M. (2017) The new RNA world: Growing evidence for long noncoding RNA functionality. Trends in Genetics 33: 665–676. [PubMed: 28870653]
    229.
    Grote P. et al. (2013) The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Developmental Cell 24: 206–214. [PMC free article: PMC4149175] [PubMed: 23369715]
    230.
    O‘Leary V.B. et al. (2015) PARTICLE, a triplex-forming long ncRNA, regulates locus-specific methylation in response to low-dose irradiation. Cell Reports 11: 474–485. [PubMed: 25900080]
    231.
    Mondal T. et al. (2015) MEG3 long noncoding RNA regulates the TGF-beta pathway genes through formation of RNA-DNA triplex structures. Nature Communications 6: 7743. [PMC free article: PMC4525211] [PubMed: 26205790]
    232.
    Postepska-Igielska A. et al. (2015) LncRNA Khps1 regulates expression of the proto-oncogene SPHK1 via triplex-mediated changes in chromatin structure. Molecular Cell 60: 626–636. [PubMed: 26590717]
    233.
    Blank-Giwojna A., Postepska-Igielska A. and Grummt I. (2019) lncRNA KHPS1 activates a poised enhancer by triplex-dependent recruitment of epigenomic regulators. Cell Reports 26: 2904–2915. [PubMed: 30865882]
    234.
    Kalwa M. et al. (2016) The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation. Nucleic Acids Research 44: 10631–10643. [PMC free article: PMC5159544] [PubMed: 27634931]
    235.
    Cloutier S.C. et al. (2016) Regulated formation of lncRNA-DNA hybrids enables faster transcriptional induction and environmental adaptation. Molecular Cell 61: 393–404. [PMC free article: PMC4744127] [PubMed: 26833086]
    236.
    Soibam B. (2017) Super-lncRNAs: Identification of lncRNAs that target super-enhancers via RNA:DNA:DNA triplex formation. RNA 23: 1729–1742. [PMC free article: PMC5648039] [PubMed: 28839111]
    237.
    Wang S. et al. (2018) LncRNA MIR100HG promotes cell proliferation in triple-negative breast cancer through triplex formation with p27 loci. Cell Death & Disease 9: 805. [PMC free article: PMC6057987] [PubMed: 30042378]
    238.
    Kuo C.-C. et al. (2019) Detection of RNA–DNA binding sites in long noncoding RNAs. Nucleic Acids Research 47: e32. [PMC free article: PMC6451187] [PubMed: 30698727]
    239.
    Arab K. et al. (2019) GADD45A binds R-loops and recruits TET1 to CpG island promoters. Nature Genetics 51: 217–223. [PMC free article: PMC6420098] [PubMed: 30617255]
    240.
    Ou M., Li X., Zhao S., Cui S. and Tu J. (2020) Long non-coding RNA CDKN2B-AS1 contributes to atherosclerotic plaque formation by forming RNA-DNA triplex in the CDKN2B promoter. EBioMedicine 55: 102694. [PMC free article: PMC7184162] [PubMed: 32335370]
    241.
    Toscano-Garibay J.D. and Aquino-Jarquin G. (2014) Transcriptional regulation mechanism mediated by miRNA–DNA•DNA triplex structure stabilized by Argonaute. Biochimica et Biophysica Acta 1839: 1079–1083. [PubMed: 25086339]
    242.
    Ariel F. et al. (2020) R-loop mediated trans action of the APOLO long noncoding RNA. Molecular Cell 77: 1055–1065. [PubMed: 31952990]
    243.
    Moison M. et al. (2021) The lncRNA APOLO interacts with the transcription factor WRKY42 to trigger root hair cell expansion in response to cold. Molecular Plant 14: 937–948. [PubMed: 33689931]
    244.
    Fonouni-Farde C. et al. (2021) Sequence-unrelated long noncoding RNAs converged to modulate the activity of conserved epigenetic machineries across kingdoms. bioRxiv: 433017.
    245.
    Ladomery M. (1997) Multifunctional proteins suggest connections between transcriptional and post-transcriptional processes. BioEssays 19: 903–909. [PubMed: 9363684]
    246.
    Matsumoto K. and Wolffe A.P. (1998) Gene regulation by Y-box proteins: Coupling control of transcription and translation. Trends in Cell Biology 8: 318–323. [PubMed: 9704408]
    247.
    Medvedovic J., Ebert A., Tagoh H. and Busslinger M. (2011) Pax5: A master regulator of B cell development and leukemogenesis, in F.W. Alt (ed.) Advances in Immunology (Academic Press, New York). [PubMed: 21970955]
    248.
    Lee N., Moss W.N., Yario T.A. and Steitz J.A. (2015) EBV noncoding RNA binds nascent RNA to drive host PAX5 to viral DNA. Cell 160: 607–618. [PMC free article: PMC4329084] [PubMed: 25662012]
    249.
    Xu Y. et al. (2021) ERα is an RNA-binding protein sustaining tumor cell survival and drug resistance. Cell 184: 5215–5229. [PMC free article: PMC8547373] [PubMed: 34559986]
    250.
    Oberosler P., Hloch P., Ramsperger U. and Stahl H. (1993) p53-catalyzed annealing of complementary single-stranded nucleic acids. The EMBO Journal 12: 2389–2396. [PMC free article: PMC413469] [PubMed: 7685274]
    251.
    Schmitt A.M. et al. (2016) An inducible long noncoding RNA amplifies DNA damage signaling. Nature Genetics 48: 1370–1376. [PMC free article: PMC5083181] [PubMed: 27668660]
    252.
    Wang X. et al. (2008) Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454: 126–130. [PMC free article: PMC2823488] [PubMed: 18509338]
    253.
    Yoneda R. et al. (2016) The binding specificity of Translocated in LipoSarcoma/FUsed in Sarcoma with lncRNA transcribed from the promoter region of cyclin D1. Cell & Bioscience 6: 4. [PMC free article: PMC4727290] [PubMed: 26816614]
    254.
    Yoneda R., Ueda N., Uranishi K., Hirasaki M. and Kurokawa R. (2020) Long noncoding RNA pncRNA-D reduces cyclin D1 gene expression and arrests cell cycle through RNA m6A modification. Journal of Biological Chemistry 295: 5626–5639. [PMC free article: PMC7186179] [PubMed: 32165496]
    255.
    Allen T.A., Von Kaenel S., Goodrich J.A. and Kugel J.F. (2004) The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock. Nature Structural & Molecular Biology 11: 816–821. [PubMed: 15300240]
    256.
    Espinoza C.A., Allen T.A., Hieb A.R., Kugel J.F. and Goodrich J.A. (2004) B2 RNA binds directly to RNA polymerase II to repress transcript synthesis. Nature Structural & Molecular Biology 11: 822–829. [PubMed: 15300239]
    257.
    Mariner P.D. et al. (2008) Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Molecular Cell 29: 499–509. [PubMed: 18313387]
    258.
    Yakovchuk P., Goodrich J.A. and Kugel J.F. (2009) B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes. Proceedings of the National Academy of Sciences USA 106: 5569–5574. [PMC free article: PMC2667051] [PubMed: 19307572]
    259.
    Ferrigno O. et al. (2001) Transposable B2 SINE elements can provide mobile RNA polymerase II promoters. Nature Genetics 28: 77–81. [PubMed: 11326281]
    260.
    Groner A.C. et al. (2010) KRAB-zinc finger proteins and KAP1 can mediate long-range transcriptional repression through heterochromatin spreading. PLOS Genetics 6: e1000869. [PMC free article: PMC2832679] [PubMed: 20221260]
    261.
    Pontis J. et al. (2019) Hominoid-specific transposable elements and KZFPs facilitate human embryonic genome activation and control transcription in naive human ESCs. Cell Stem Cell 24: 724–735. [PMC free article: PMC6509360] [PubMed: 31006620]
    262.
    Turelli P. et al. (2020) Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons. Science Advances 6: eaba3200. [PMC free article: PMC7455193] [PubMed: 32923624]
    263.
    Birtle Z. and Ponting C.P. (2006) Meisetz and the birth of the KRAB motif. Bioinformatics 22: 2841–2845. [PubMed: 17032681]
    264.
    Urrutia R. (2003) KRAB-containing zinc-finger repressor proteins. Genome Biology 4: 231. [PMC free article: PMC328446] [PubMed: 14519192]
    265.
    Huntley S. et al. (2006) A comprehensive catalog of human KRAB-associated zinc finger genes: Insights into the evolutionary history of a large family of transcriptional repressors. Genome Research 16: 669–677. [PMC free article: PMC1457042] [PubMed: 16606702]
    266.
    Emerson R.O. and Thomas J.H. (2009) Adaptive evolution in zinc finger transcription factors. PLOS Genetics 5: e1000325. [PMC free article: PMC2604467] [PubMed: 19119423]
    267.
    Lupo A. et al. (2013) KRAB-zinc finger proteins: A repressor family displaying multiple biological functions. Current Genomics 14: 268–278. [PMC free article: PMC3731817] [PubMed: 24294107]
    268.
    Imbeault M., Helleboid P.-Y. and Trono D. (2017) KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks. Nature 543: 550–554. [PubMed: 28273063]
    269.
    Yang P., Wang Y. and Macfarlan T.S. (2017) The role of KRAB-ZFPs in transposable element repression and mammalian evolution. Trends in Genetics 33: 871–881. [PMC free article: PMC5659910] [PubMed: 28935117]
    270.
    Cosby R.L. et al. (2021) Recurrent evolution of vertebrate transcription factors by transposase capture. Science 371: eabc6405. [PMC free article: PMC8186458] [PubMed: 33602827]
    271.
    Minezaki Y., Homma K., Kinjo A.R. and Nishikawa K. (2006) Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation. Journal of Molecular Biology 359: 1137–1149. [PubMed: 16697407]
    272.
    Liu J. et al. (2006) Intrinsic disorder in transcription factors. Biochemistry 45: 6873–6888. [PMC free article: PMC2538555] [PubMed: 16734424]
    273.
    Guo X., Bulyk M.L. and Hartemink A.J. (2012) Intrinsic disorder within and flanking the DNA-binding domains of human transcription factors. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 2012: 104–115. [PMC free article: PMC3327284] [PubMed: 22174267]
    274.
    Staby L. et al. (2017) Eukaryotic transcription factors: Paradigms of protein intrinsic disorder. Biochemical Journal 474: 2509–2532. [PubMed: 28701416]
    275.
    Brodsky S. et al. (2020) Intrinsically disordered regions direct transcription factor in vivo binding specificity. Molecular Cell 79: 459–471. [PubMed: 32553192]
    276.
    Mattick J.S., Taft R.J. and Faulkner G.J. (2010) A global view of genomic information--moving beyond the gene and the master regulator. Trends in Genetics 26: 21–28. [PubMed: 19944475]
    277.
    Erdmann R.M. and Picard C.L. (2020) RNA-directed DNA methylation. PLOS Genetics 16: e1009034. [PMC free article: PMC7544125] [PubMed: 33031395]
    278.
    Sigman M.J. et al. (2021) An siRNA-guided Argonaute protein directs RNA polymerase V to initiate DNA methylation. Nature Plants 7: 1461–1474. [PMC free article: PMC8592841] [PubMed: 34750500]
    279.
    Morris K.V., Chan S.W., Jacobsen S.E. and Looney D.J. (2004) Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305: 1289–1292. [PubMed: 15297624]
    280.
    Castel S.E. and Martienssen R.A. (2013) RNA interference in the nucleus: Roles for small RNAs in transcription, epigenetics and beyond. Nature Reviews Genetics 14: 100–112. [PMC free article: PMC4205957] [PubMed: 23329111]
    281.
    Janowski B.A. et al. (2006) Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nature Structural & Molecular Biology 13: 787–792. [PubMed: 16936728]
    282.
    Kim D.H., Villeneuve L.M., Morris K.V. and Rossi J.J. (2006) Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nature Structural & Molecular Biology 13: 793–797. [PubMed: 16936726]
    283.
    Vagin V.V. et al. (2006) A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313: 320–324. [PubMed: 16809489]
    284.
    Benetti R. et al. (2008) A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nature Structural & Molecular Biology 15: 268–279. [PMC free article: PMC2990406] [PubMed: 18311151]
    285.
    Aravin A.A. et al. (2008) A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Molecular Cell 31: 785–799. [PMC free article: PMC2730041] [PubMed: 18922463]
    286.
    Ting A.H., Schuebel K.E., Herman J.G. and Baylin S.B. (2005) Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation. Nature Genetics 37: 906–910. [PMC free article: PMC2659476] [PubMed: 16025112]
    287.
    Jeffery L. and Nakielny S. (2004) Components of the DNA methylation system of chromatin control are RNA-binding proteins. Journal of Biological Chemistry 279: 49479–49487. [PubMed: 15342650]
    288.
    Mohammad F., Mondal T., Guseva N., Pandey G.K. and Kanduri C. (2010) Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development 137: 2493–2499. [PubMed: 20573698]
    289.
    Di Ruscio A. et al. (2013) DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 503: 371–376. [PMC free article: PMC3870304] [PubMed: 24107992]
    290.
    Merry C.R. et al. (2015) DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer. Human Molecular Genetics 24: 6240–6253. [PMC free article: PMC4599679] [PubMed: 26307088]
    291.
    Somasundaram S. et al. (2018) The DNMT1-associated lincRNA DACOR1 reprograms genome-wide DNA methylation in colon cancer. Clinical Epigenetics 10: 127. [PMC free article: PMC6196572] [PubMed: 30348202]
    292.
    Weiss A., Keshet I., Razin A. and Cedar H. (1996) DNA demethylation in vitro: Involvement of RNA. Cell 86: 709–718. [PubMed: 8797818]
    293.
    Jost J.-P., Frémont M., Siegmann M. and Hofsteenge J. (1997) The RNA moiety of chick embryo 5-methylcytosine-DNA glycosylase targets DNA demethylation. Nucleic Acids Research 25: 4545–4550. [PMC free article: PMC147099] [PubMed: 9358164]
    294.
    Imamura T. et al. (2004) Non-coding RNA directed DNA demethylation of Sphk1 CpG island. Biochemical and Biophysical Research Communications 322: 593–600. [PubMed: 15325271]
    295.
    Sytnikova Y.A., Kubarenko A.V., Schäfer A., Weber A.N.R. and Niehrs C. (2011) Gadd45a Is an RNA binding protein and is localized in nuclear speckles. PLOS ONE 6: e14500. [PMC free article: PMC3017548] [PubMed: 21249130]
    296.
    He C. et al. (2016) High-resolution mapping of RNA-binding regions in the nuclear proteome of embryonic stem cells. Molecular Cell 64: 416–430. [PMC free article: PMC5222606] [PubMed: 27768875]
    297.
    He C. et al. (2021) TET2 chemically modifies tRNAs and regulates tRNA fragment levels. Nature Structural & Molecular Biology 28: 62–70. [PMC free article: PMC7855721] [PubMed: 33230319]
    298.
    Guallar D. et al. (2018) RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nature Genetics 50: 443–451. [PMC free article: PMC5862756] [PubMed: 29483655]
    299.
    Landers C.C. et al. (2021) Ectopic expression of pericentric HSATII RNA results in nuclear RNA accumulation, MeCP2 recruitment, and cell division defects. Chromosoma 130: 75–90. [PMC free article: PMC7889552] [PubMed: 33585981]
    300.
    O’Leary V.B. et al. (2017) Long non-coding RNA PARTICLE bridges histone and DNA methylation. Scientific Reports 7: 1790. [PMC free article: PMC5431818] [PubMed: 28496150]
    301.
    Tresaugues L. et al. (2006) Structural characterization of Set1 RNA recognition motifs and their role in histone H3 lysine 4 methylation. Journal of Molecular Biology 359: 1170–1181. [PubMed: 16787775]
    302.
    Akhtar A., Zink D. and Becker P.B. (2000) Chromodomains are protein-RNA interaction modules. Nature 407: 405–409. [PubMed: 11014199]
    303.
    Yap K.L. et al. (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Molecular Cell 38: 662–674. [PMC free article: PMC2886305] [PubMed: 20541999]
    304.
    Pek J.W., Anand A. and Kai T. (2012) Tudor domain proteins in development. Development 139: 2255–2266. [PubMed: 22669818]
    305.
    Zhao J., Sun B.K., Erwin J.A., Song J.J. and Lee J.T. (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322: 750–756. [PMC free article: PMC2748911] [PubMed: 18974356]
    306.
    Zhao J. et al. (2010) Genome-wide identification of polycomb-associated RNAs by RIP-seq. Molecular Cell 40: 939–953. [PMC free article: PMC3021903] [PubMed: 21172659]
    307.
    Kanhere A. et al. (2010) Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Molecular Cell 38: 675–688. [PMC free article: PMC2886029] [PubMed: 20542000]
    308.
    Cifuentes-Rojas C., Hernandez A.J., Sarma K. and Lee J.T. (2014) Regulatory interactions between RNA and polycomb repressive complex 2. Molecular Cell 55: 171–185. [PMC free article: PMC4107928] [PubMed: 24882207]
    309.
    Kaneko S. et al. (2014) Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Molecular Cell 53: 290–300. [PMC free article: PMC4026005] [PubMed: 24374312]
    310.
    Betancur J.G. and Tomari Y. (2015) Cryptic RNA-binding by PRC2 components EZH2 and SUZ12. RNA Biology 12: 959–965. [PMC free article: PMC4615636] [PubMed: 26177152]
    311.
    Tsai M.C. et al. (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329: 689–693. [PMC free article: PMC2967777] [PubMed: 20616235]
    312.
    Huang R.C. and Bonner J. (1965) Histone-bound RNA, a component of native nucleohistone. Proceedings of the National Academy of Sciences USA 54: 960–967. [PMC free article: PMC219771] [PubMed: 5217473]
    313.
    Benjamin W., Levander O.A., Gellhorn A. and DeBellis R.H. (1966) An RNA-histone complex in mammalian cells: The isolation and characterization of a new RNA species. Proceedings of the National Academy of Sciences USA 55: 858–865. [PMC free article: PMC224242] [PubMed: 5219694]
    314.
    Denisenko O., Shnyreva M., Suzuki H. and Bomsztyk K. (1998) Point mutations in the WD40 domain of Eed block its interaction with Ezh2. Molecular and Cellular Biology 18: 5634–5642. [PMC free article: PMC109149] [PubMed: 9742080]
    315.
    Zhang H. et al. (2004) The C. elegans Polycomb gene SOP-2 encodes an RNA binding protein. Molecular Cell 14: 841–847. [PubMed: 15200961]
    316.
    Bernstein E. et al. (2006) Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. Molecular Cell Biology 26: 2560–2569. [PMC free article: PMC1430336] [PubMed: 16537902]
    317.
    Schmitt S., Prestel M. and Paro R. (2005) Intergenic transcription through a polycomb group response element counteracts silencing. Genes & Development 19: 697–708. [PMC free article: PMC1065723] [PubMed: 15741315]
    318.
    Rinn J.L. et al. (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129: 1311–1323. [PMC free article: PMC2084369] [PubMed: 17604720]
    319.
    Sessa L. et al. (2007) Noncoding RNA synthesis and loss of polycomb group repression accompanies the colinear activation of the human HOXA cluster. RNA 13: 223–239. [PMC free article: PMC1781374] [PubMed: 17185360]
    320.
    Nagano T. et al. (2008) The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322: 1717–1720. [PubMed: 18988810]
    321.
    Pandey R.R. et al. (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Molecular Cell 32: 232–246. [PubMed: 18951091]
    322.
    Kanduri C. (2016) Long noncoding RNAs: Lessons from genomic imprinting. Biochimica et Biophysica Acta 1859: 102–111. [PubMed: 26004516]
    323.
    Dinger M.E. et al. (2008) Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Research 18: 1433–1445. [PMC free article: PMC2527704] [PubMed: 18562676]
    324.
    Wang K.C. et al. (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472: 120–124. [PMC free article: PMC3670758] [PubMed: 21423168]
    325.
    Gomez J.A. et al. (2013) The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-gamma locus. Cell 152: 743–754. [PMC free article: PMC3577098] [PubMed: 23415224]
    326.
    Yang Y.W. et al. (2014) Essential role of lncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency. eLife 3: e02046. [PMC free article: PMC3921674] [PubMed: 24521543]
    327.
    He X. et al. (2015) An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes. Nucleic Acids Research 43: 3712–3725. [PMC free article: PMC4402533] [PubMed: 25779046]
    328.
    Deng C. et al. (2016) HoxBlinc RNA recruits Set1/MLL complexes to activate Hox gene expression patterns and mesoderm lineage development. Cell Reports 14: 103–114. [PMC free article: PMC4706800] [PubMed: 26725110]
    329.
    Wang X.Q.D. and Dostie J. (2017) Reciprocal regulation of chromatin state and architecture by HOTAIRM1 contributes to temporal collinear HOXA gene activation. Nucleic Acids Research 45: 1091–1104. [PMC free article: PMC5388432] [PubMed: 28180285]
    330.
    Alexanian M. et al. (2017) A transcribed enhancer dictates mesendoderm specification in pluripotency. Nature Communications 8: 1806. [PMC free article: PMC5703900] [PubMed: 29180618]
    331.
    Su W. et al. (2017) Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer. Molecular Cancer 16: 142. [PMC free article: PMC5568204] [PubMed: 28830551]
    332.
    Luo H. et al. (2019) HOTTIP lncRNA promotes hematopoietic stem cell self-renewal leading to AML-like disease in mice. Cancer Cell 36: 645–659. [PMC free article: PMC6917035] [PubMed: 31786140]
    333.
    Fanucchi S. et al. (2019) Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments. Nature Genetics 51: 138–150. [PubMed: 30531872]
    334.
    Hu A. et al. (2021) Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression. Journal of Translational Medicine 19: 95. [PMC free article: PMC7927245] [PubMed: 33653378]
    335.
    Wang Y. et al. (2018) Overexpressing lncRNA LAIR increases grain yield and regulates neighbouring gene cluster expression in rice. Nature Communications 9: 3516. [PMC free article: PMC6115402] [PubMed: 30158538]
    336.
    Khalil A.M. et al. (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proceedings of the National Academy of Sciences USA 106: 11667–11672. [PMC free article: PMC2704857] [PubMed: 19571010]
    337.
    Kotake Y. et al. (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30: 1956–1962. [PMC free article: PMC3230933] [PubMed: 21151178]
    338.
    Shore A.N. et al. (2012) Pregnancy-induced noncoding RNA (PINC) associates with polycomb repressive complex 2 and regulates mammary epithelial differentiation. PLOS Genetics 8: e1002840. [PMC free article: PMC3406180] [PubMed: 22911650]
    339.
    Davidovich C. and Cech T.R. (2015) The recruitment of chromatin modifiers by long noncoding RNAs: Lessons from PRC2. RNA 21: 2007–2022. [PMC free article: PMC4647455] [PubMed: 26574518]
    340.
    Marchese F.P., Raimondi I. and Huarte M. (2017) The multidimensional mechanisms of long noncoding RNA function. Genome Biology 18: 206. [PMC free article: PMC5663108] [PubMed: 29084573]
    341.
    Dill T.L., Carroll A., Pinheiro A., Gao J. and Naya F.J. (2021) The long noncoding RNA Meg3 regulates myoblast plasticity and muscle regeneration through epithelial-mesenchymal transition. Development 148: dev194027. [PubMed: 33298462]
    342.
    Balas M.M. et al. (2021) Establishing RNA-RNA interactions remodels lncRNA structure and promotes PRC2 activity. Science Advances 7: eabc9191. [PMC free article: PMC8046370] [PubMed: 33853770]
    343.
    Long Y. et al. (2020) RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells. Nature Genetics 52: 931–938. [PMC free article: PMC10353856] [PubMed: 32632336]
    344.
    Wang X. et al. (2017) Targeting of polycomb repressive complex 2 to RNA by short repeats of consecutive guanines. Molecular Cell 65: 1056–1067. [PubMed: 28306504]
    345.
    Beltran M. et al. (2019) G-tract RNA removes Polycomb repressive complex 2 from genes. Nature Structural & Molecular Biology 26: 899–909. [PMC free article: PMC6778522] [PubMed: 31548724]
    346.
    Zhang Q. et al. (2019) RNA exploits an exposed regulatory site to inhibit the enzymatic activity of PRC2. Nature Structural & Molecular Biology 26: 237–247. [PMC free article: PMC6736635] [PubMed: 30833789]
    347.
    Plys A.J. et al. (2019) Phase separation of Polycomb-repressive complex 1 is governed by a charged disordered region of CBX2. Genes & Development 33: 1–15. [PMC free article: PMC6601514] [PubMed: 31171700]
    348.
    Davidovich C., Zheng L., Goodrich K.J. and Cech T.R. (2013) Promiscuous RNA binding by Polycomb repressive complex 2. Nature Structural & Molecular Biology 20: 1250–1257. [PMC free article: PMC3823624] [PubMed: 24077223]
    349.
    Davidovich C. et al. (2015) Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA. Molecular Cell 57: 552–558. [PMC free article: PMC4320675] [PubMed: 25601759]
    350.
    Martinez A.M. and Cavalli G. (2006) The role of polycomb group proteins in cell cycle regulation during development. Cell Cycle 5: 1189–1197. [PubMed: 16721063]
    351.
    Bantignies F. and Cavalli G. (2006) Cellular memory and dynamic regulation of polycomb group proteins. Current Opinion in Cell Biology 18: 275–283. [PubMed: 16650749]
    352.
    Boyer L.A. et al. (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441: 349–353. [PubMed: 16625203]
    353.
    Lee T.I. et al. (2006) Control of developmental regulators by polycomb in human embryonic stem cells. Cell 125: 301–313. [PMC free article: PMC3773330] [PubMed: 16630818]
    354.
    Poynter S.T. and Kadoch C. (2016) Polycomb and trithorax opposition in development and disease. Wiley Interdisciplinary Reviews Developmental Biology 5: 659–688. [PMC free article: PMC5518792] [PubMed: 27581385]
    355.
    Schuettengruber B., Bourbon H.-M., Di Croce L. and Cavalli G. (2017) Genome regulation by Polycomb and Trithorax: 70 years and counting. Cell 171: 34–57. [PubMed: 28938122]
    356.
    Herzog V.A. et al. (2014) A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element. Nature Genetics 46: 973–981. [PMC free article: PMC4270207] [PubMed: 25108384]
    357.
    Beltran M. et al. (2016) The interaction of PRC2 with RNA or chromatin is mutually antagonistic. Genome Research 26: 896–907. [PMC free article: PMC4937559] [PubMed: 27197219]
    358.
    Zovoilis A., Cifuentes-Rojas C., Chu H.-P., Hernandez A.J. and Lee J.T. (2016) Destabilization of B2 RNA by EZH2 activates the stress response. Cell 167: 1788–1802. [PMC free article: PMC5552366] [PubMed: 27984727]
    359.
    Singh I. et al. (2018) MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolar organization. Nature Genetics 50: 990–1001. [PubMed: 29867223]
    360.
    Kang X., Zhao Y., Van Arsdell G., Nelson S.F. and Touma M. (2020) Ppp1r1b-lncRNA inhibits PRC2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human. RNA 26: 481–491. [PMC free article: PMC7075267] [PubMed: 31953255]
    361.
    Rosenberg M. et al. (2021) Motif-driven interactions between RNA and PRC2 are rheostats that regulate transcription elongation. Nature Structural & Molecular Biology 28: 103–117. [PMC free article: PMC8050941] [PubMed: 33398172]
    362.
    Guo Y., Zhao S. and Wang G.G. (2021) Polycomb gene silencing mechanisms: PRC2 chromatin targeting, H3K27me3 ‘readout’, and phase separation-based compaction. Trends in Genetics 37: 547–565. [PMC free article: PMC8119337] [PubMed: 33494958]
    363.
    Kraft K. et al. (2020) Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation. bioRxiv: 2020.07.27.223438. [PMC free article: PMC9295753] [PubMed: 35617427]
    364.
    Ringrose L. (2017) Noncoding RNAs in Polycomb and Trithorax regulation: A quantitative perspective. Annual Review of Genetics 51: 385–411. [PubMed: 28934594]
    365.
    Jantrapirom S. et al. (2021) Long noncoding RNA-dependent methylation of nonhistone proteins. WIREs RNA 12: e1661. [PubMed: 33913612]
    366.
    Butler A.A., Johnston D.R., Kaur S. and Lubin F.D. (2019) Long noncoding RNA NEAT1 mediates neuronal histone methylation and age-related memory impairment. Science Signaling 12: eaaw9277. [PMC free article: PMC7219525] [PubMed: 31266852]
    367.
    Budhavarapu V.N., Chavez M. and Tyler J.K. (2013) How is epigenetic information maintained through DNA replication? Epigenetics & Chromatin 6: 32. [PMC free article: PMC3852060] [PubMed: 24225278]
    368.
    Kanduri C., Whitehead J. and Mohammad F. (2009) The long and the short of it: RNA-directed chromatin asymmetry in mammalian X-chromosome inactivation. FEBS Letters 583: 857–864. [PubMed: 19302783]
    369.
    Gendrel A.-V. and Heard E. (2014) Noncoding RNAs and epigenetic mechanisms during X-chromosome inactivation. Annual Review of Cell and Developmental Biology 30: 561–580. [PubMed: 25000994]
    370.
    Brown C.J. et al. (1992) The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71: 527–542. [PubMed: 1423611]
    371.
    Chu C. et al. (2015) Systematic discovery of Xist RNA binding proteins. Cell 161: 404–416. [PMC free article: PMC4425988] [PubMed: 25843628]
    372.
    Minajigi A. et al. (2015) Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science 349: aab2276. [PMC free article: PMC4845908] [PubMed: 26089354]
    373.
    Smola M.J. et al. (2016) SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells. Proceedings of the National Academy of Sciences USA 113: 10322–10327. [PMC free article: PMC5027438] [PubMed: 27578869]
    374.
    Lu Z. et al. (2016) RNA duplex map in living cells reveals higher-order transcriptome structure. Cell 165: 1267–1279. [PMC free article: PMC5029792] [PubMed: 27180905]
    375.
    Sunwoo H., Wu J.Y. and Lee J.T. (2015) The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells. Proceedings of the National Academy of Sciences USA 112: E4216–25. [PMC free article: PMC4534268] [PubMed: 26195790]
    376.
    Markaki Y. et al. (2021) Xist nucleates local protein gradients to propagate silencing across the X chromosome. Cell 184: 6174–6192. [PMC free article: PMC8671326] [PubMed: 34813726]
    377.
    Chaumeil J., Le Baccon P., Wutz A. and Heard E. (2006) A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes & Development 20: 2223–2237. [PMC free article: PMC1553206] [PubMed: 16912274]
    378.
    Yamada N. et al. (2015) Xist exon 7 contributes to the stable localization of Xist RNA on the inactive X-chromosome. PLOS Genetics 11: e1005430. [PMC free article: PMC4526699] [PubMed: 26244333]
    379.
    Sunwoo H., Colognori D., Froberg J.E., Jeon Y. and Lee J.T. (2017) Repeat E anchors Xist RNA to the inactive X chromosomal compartment through CDKN1A-interacting protein (CIZ1). Proceedings of the National Academy of Sciences USA 114: 10654–10659. [PMC free article: PMC5635913] [PubMed: 28923964]
    380.
    Yue M. et al. (2017) Xist RNA repeat E is essential for ASH2L recruitment to the inactive X and regulates histone modifications and escape gene expression. PLOS Genetics 13: e1006890. [PMC free article: PMC5521851] [PubMed: 28686623]
    381.
    Wang Y. et al. (2019) Identification of a Xist silencing domain by tiling CRISPR. Scientific Reports 9: 2408. [PMC free article: PMC6382781] [PubMed: 30787302]
    382.
    Wei G., Almeida M., Bowness J.S., Nesterova T.B. and Brockdorff N. (2021) Xist Repeats B and C, but not Repeat A, mediate de novo recruitment of the Polycomb system in X chromosome inactivation. Developmental Cell 56: 1234–1235. [PubMed: 33945783]
    383.
    Csankovszki G., Nagy A. and Jaenisch R. (2001) Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. Journal of Cell Biology 153: 773–784. [PMC free article: PMC2192370] [PubMed: 11352938]
    384.
    McHugh C.A. et al. (2015) The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature 521: 232–236. [PMC free article: PMC4516396] [PubMed: 25915022]
    385.
    Yu B. et al. (2021) B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells. Cell 184: 1790–1803. [PMC free article: PMC9196326] [PubMed: 33735607]
    386.
    Plath K. et al. (2004) Developmentally regulated alterations in polycomb repressive complex 1 proteins on the inactive X chromosome. Journal of Cell Biology 167: 1025–1035. [PMC free article: PMC2172612] [PubMed: 15596546]
    387.
    Maenner S. et al. (2010) 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLOS Biology 8: e1000276. [PMC free article: PMC2796953] [PubMed: 20052282]
    388.
    Splinter E. et al. (2011) The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA. Genes & Development 25: 1371–1383. [PMC free article: PMC3134081] [PubMed: 21690198]
    389.
    Nora E.P. et al. (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485: 381–385. [PMC free article: PMC3555144] [PubMed: 22495304]
    390.
    Engreitz J.M. et al. (2013) The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341: 1237973. [PMC free article: PMC3778663] [PubMed: 23828888]
    391.
    van Bemmel J.G. et al. (2019) The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist. Nature Genetics 51: 1024–1034. [PMC free article: PMC6551226] [PubMed: 31133748]
    392.
    Kriz A.J., Colognori D., Sunwoo H., Nabet B. and Lee J.T. (2021) Balancing cohesin eviction and retention prevents aberrant chromosomal interactions, Polycomb-mediated repression, and X-inactivation. Molecular Cell 81: 1970–1987. [PMC free article: PMC8106664] [PubMed: 33725485]
    393.
    Cerase A. et al. (2019) Phase separation drives X-chromosome inactivation: A hypothesis. Nature Structural & Molecular Biology 26: 331–334. [PubMed: 31061525]
    394.
    Pandya-Jones A. et al. (2020) A protein assembly mediates Xist localization and gene silencing. Nature 587: 145–151. [PMC free article: PMC7644664] [PubMed: 32908311]
    395.
    Chow J.C. et al. (2010) LINE-1 activity in facultative heterochromatin formation during X chromosome inactivation. Cell 141: 956–969. [PubMed: 20550932]
    396.
    Tannan N.B. et al. (2014) DNA methylation profiling in X;autosome translocations supports a role for L1 repeats in the spread of X chromosome inactivation. Human Molecular Genetics 23: 1224–1236. [PMC free article: PMC3919006] [PubMed: 24186870]
    397.
    Brockdorff N. (2018) Local tandem repeat expansion in Xist RNA as a model for the functionalisation of ncRNA. Noncoding RNA 4: 28. [PMC free article: PMC6316617] [PubMed: 30347781]
    398.
    Carter A.C. et al. (2020) Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation. eLife 9: e54508. [PMC free article: PMC7282817] [PubMed: 32379046]
    399.
    Loda A. and Heard E. (2019) Xist RNA in action: Past, present, and future. PLOS Genetics 15: e1008333. [PMC free article: PMC6752956] [PubMed: 31537017]
    400.
    Lyon M.F. (1998) X-Chromosome inactivation: A repeat hypothesis. Cytogenetic and Genome Research 80: 133–137. [PubMed: 9678347]
    401.
    Lyon M.F. (2000) LINE-1 elements and X chromosome inactivation: A function for “junk” DNA? Proceedings of the National Academy of Sciences USA 97: 6248–6249. [PMC free article: PMC33995] [PubMed: 10841528]
    402.
    Matsuno Y., Yamashita T., Wagatsuma M. and Yamakage H. (2019) Convergence in LINE-1 nucleotide variations can benefit redundantly forming triplexes with lncRNA in mammalian X-chromosome inactivation. Mobile DNA 10: 33. [PMC free article: PMC6664574] [PubMed: 31384315]
    403.
    Yildirim E. et al. (2013) Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 152: 727–742. [PMC free article: PMC3875356] [PubMed: 23415223]
    404.
    Sado T., Wang Z., Sasaki H. and Li E. (2001) Regulation of imprinted X-chromosome inactivation in mice by Tsix. Development 128: 1275–1286. [PubMed: 11262229]
    405.
    Spencer R.J. et al. (2011) A boundary element between Tsix and Xist binds the chromatin insulator Ctcf and contributes to initiation of X-chromosome inactivation. Genetics 189: 441–454. [PMC free article: PMC3189804] [PubMed: 21840866]
    406.
    Morey C. et al. (2004) The region 3′ to Xist mediates X chromosome counting and H3 Lys-4 dimethylation within the Xist gene. EMBO Journal 23: 594–604. [PMC free article: PMC1271805] [PubMed: 14749728]
    407.
    Tian D., Sun S. and Lee J.T. (2010) The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 143: 390–403. [PMC free article: PMC2994261] [PubMed: 21029862]
    408.
    Chureau C. et al. (2011) Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region. Human Molecular Genetics 20: 705–718. [PubMed: 21118898]
    409.
    Sun S. et al. (2013) Jpx RNA activates Xist by evicting CTCF. Cell 153: 1537–1551. [PMC free article: PMC3777401] [PubMed: 23791181]
    410.
    Karner H. et al. (2020) Functional conservation of lncRNA JPX despite sequence and structural divergence. Journal of Molecular Biology 432: 283–300. [PubMed: 31518612]
    411.
    Casanova M. et al. (2019) A primate-specific retroviral enhancer wires the XACT lncRNA into the core pluripotency network in humans. Nature Communications 10: 5652. [PMC free article: PMC6906429] [PubMed: 31827084]
    412.
    Anguera M.C. et al. (2011) Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain. PLOS Genetics 7: e1002248. [PMC free article: PMC3164691] [PubMed: 21912526]
    413.
    Yang F. et al. (2015) The lncRNA Firre anchors the inactive X chromosome to the nucleolus by binding CTCF and maintains H3K27me3 methylation. Genome Biology 16: 52. [PMC free article: PMC4391730] [PubMed: 25887447]
    414.
    Hacisuleyman E. et al. (2014) Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nature Structural & Molecular Biology 21: 198–206. [PMC free article: PMC3950333] [PubMed: 24463464]
    415.
    Hacisuleyman E., Shukla C.J., Weiner C.L. and Rinn J.L. (2016) Function and evolution of local repeats in the Firre locus. Nature Communications 7: 11021. [PMC free article: PMC4820808] [PubMed: 27009974]
    416.
    Lewandowski J.P. et al. (2019) The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesis. Nature Communications 10: 5137. [PMC free article: PMC6853988] [PubMed: 31723143]
    417.
    Ogawa Y., Sun B.K. and Lee J.T. (2008) Intersection of the RNA interference and X-inactivation pathways. Science 320: 1336–1341. [PMC free article: PMC2584363] [PubMed: 18535243]
    418.
    Nesterova T.B. et al. (2008) Dicer regulates Xist promoter methylation in ES cells indirectly through transcriptional control of Dnmt3a. Epigenetics & Chromatin 1: 2. [PMC free article: PMC2577046] [PubMed: 19014663]
    419.
    Patil D.P. et al. (2016) m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537: 369–373. [PMC free article: PMC5509218] [PubMed: 27602518]
    420.
    Irvine D.V. et al. (2006) Argonaute slicing is required for heterochromatic silencing and spreading. Science 313: 1134–1137. [PubMed: 16931764]
    421.
    Li L.C. et al. (2006) Small dsRNAs induce transcriptional activation in human cells. Proceedings of the National Academy of Sciences USA 103: 17337–17342. [PMC free article: PMC1859931] [PubMed: 17085592]
    422.
    Kelley R.L. (2004) Path to equality strewn with roX. Developmental Biology 269: 18–25. [PubMed: 15081354]
    423.
    Park S.-W., Kuroda M.I. and Park Y. (2008) Regulation of histone H4 Lys16 acetylation by predicted alternative secondary structures in roX noncoding RNAs. Molecular and Cellular Biology 28: 4952–4962. [PMC free article: PMC2519712] [PubMed: 18541664]
    424.
    Valsecchi C.I.K. et al. (2020) RNA nucleation by MSL2 induces selective X chromosome compartmentalization. Nature 589: 137–142. [PubMed: 33208948]
    425.
    Ptashne M. (1988) How eukaryotic transcriptional activators work. Nature 335: 683–689. [PubMed: 3050531]
    426.
    Buecker C. and Wysocka J. (2012) Enhancers as information integration hubs in development: Lessons from genomics. Trends in Genetics 28: 276–284. [PMC free article: PMC5064438] [PubMed: 22487374]
    427.
    Smith E. and Shilatifard A. (2014) Enhancer biology and enhanceropathies. Nature Structural & Molecular Biology 21: 210–219. [PubMed: 24599251]
    428.
    Shlyueva D., Stampfel G. and Stark A. (2014) Transcriptional enhancers: From properties to genome-wide predictions. Nature Reviews Genetics 15: 272–286. [PubMed: 24614317]
    429.
    Krijger P.H.L. and de Laat W. (2016) Regulation of disease-associated gene expression in the 3D genome. Nature Reviews Molecular Cell Biology 17: 771–782. [PubMed: 27826147]
    430.
    Henriques T. et al. (2018) Widespread transcriptional pausing and elongation control at enhancers. Genes & Development 32: 26–41. [PMC free article: PMC5828392] [PubMed: 29378787]
    431.
    Souaid C., Bloyer S. and Noordermeer D. (2018) Promoter–enhancer looping and regulatory neighborhoods: Gene regulation in the framework of topologically associating domains, in C. Lavelle and J.-M. Victor (eds.) Nuclear Architecture and Dynamics (Academic Press, New York).
    432.
    Gribnau J., Diderich K., Pruzina S., Calzolari R. and Fraser P. (2000) Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus. Molecular Cell 5: 377–386. [PubMed: 10882078]
    433.
    Masternak K., Peyraud N., Krawczyk M., Barras E. and Reith W. (2003) Chromatin remodeling and extragenic transcription at the MHC class II locus control region. Nature Immunology 4: 132–137. [PubMed: 12524537]
    434.
    Ling J. et al. (2004) HS2 enhancer function is blocked by a transcriptional terminator inserted between the enhancer and the promoter. Journal of Biological Chemistry 279: 51704–51713. [PubMed: 15465832]
    435.
    Delpretti S. et al. (2013) Multiple enhancers regulate Hoxd genes and the Hotdog lncRNA during cecum budding. Cell Reports 5: 137–150. [PubMed: 24075990]
    436.
    Core L.J. et al. (2014) Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers. Nature Genetics 46: 1311–1320. [PMC free article: PMC4254663] [PubMed: 25383968]
    437.
    Kim T.-K., Hemberg M. and Gray J.M. (2015) Enhancer RNAs: A class of long noncoding RNAs synthesized at enhancers. Cold Spring Harbor Perspectives in Biology 7: a018622. [PMC free article: PMC4292161] [PubMed: 25561718]
    438.
    Dong X. et al. (2018) Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease. Nature Neuroscience 21: 1482–1492. [PMC free article: PMC6334654] [PubMed: 30224808]
    439.
    Azofeifa J.G. et al. (2018) Enhancer RNA profiling predicts transcription factor activity. Genome Research 28: 334–344. [PMC free article: PMC5848612] [PubMed: 29449408]
    440.
    Grossman S.R. et al. (2018) Positional specificity of different transcription factor classes within enhancers. Proceedings of the National Academy of Sciences USA 115: E7222–30. [PMC free article: PMC6065035] [PubMed: 29987030]
    441.
    Arnold P.R., Wells A.D. and Li X.C. (2020) Diversity and emerging roles of enhancer RNA in regulation of gene expression and cell fate. Frontiers in Cell and Developmental Biology 7: 377. [PMC free article: PMC6971116] [PubMed: 31993419]
    442.
    Li W., Notani D. and Rosenfeld M.G. (2016) Enhancers as non-coding RNA transcription units: Recent insights and future perspectives. Nature Reviews Genetics 17: 207–223. [PubMed: 26948815]
    443.
    Arner E. et al. (2015) Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science 347: 1010–1014. [PMC free article: PMC4681433] [PubMed: 25678556]
    444.
    Kim T.-K. et al. (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465: 182–187. [PMC free article: PMC3020079] [PubMed: 20393465]
    445.
    Hnisz D. et al. (2013) Super-enhancers in the control of cell identity and disease. Cell 155: 934–947. [PMC free article: PMC3841062] [PubMed: 24119843]
    446.
    Hon C.-C. et al. (2017) An atlas of human long non-coding RNAs with accurate 5′ ends. Nature 543: 199–204. [PMC free article: PMC6857182] [PubMed: 28241135]
    447.
    Lewis M.W., Li S. and Franco H.L. (2019) Transcriptional control by enhancers and enhancer RNAs. Transcription 10: 171–186. [PMC free article: PMC6948965] [PubMed: 31791217]
    448.
    De Santa F. et al. (2010) A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLOS Biology 8: e1000384. [PMC free article: PMC2867938] [PubMed: 20485488]
    449.
    Wang D. et al. (2011) Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474: 390–394. [PMC free article: PMC3117022] [PubMed: 21572438]
    450.
    Wu H. et al. (2014) Tissue-specific RNA expression marks distant-acting developmental enhancers. PLOS Genetics 10: e1004610. [PMC free article: PMC4154669] [PubMed: 25188404]
    451.
    Kim Y.W., Lee S., Yun J. and Kim A. (2015) Chromatin looping and eRNA transcription precede the transcriptional activation of gene in the beta-globin locus. Bioscience Reports 35: e00179. [PMC free article: PMC4370096] [PubMed: 25588787]
    452.
    Sartorelli V. and Lauberth S.M. (2020) Enhancer RNAs are an important regulatory layer of the epigenome. Nature Structural & Molecular Biology 27: 521–528. [PMC free article: PMC7343394] [PubMed: 32514177]
    453.
    Carullo N.V.N. et al. (2020) Enhancer RNAs predict enhancer–gene regulatory links and are critical for enhancer function in neuronal systems. Nucleic Acids Research 48: 9550–9570. [PMC free article: PMC7515708] [PubMed: 32810208]
    454.
    Lin C.Y. et al. (2016) Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature 530: 57–62. [PMC free article: PMC5168934] [PubMed: 26814967]
    455.
    Zhao Y. et al. (2016) Activation of P-TEFb by androgen receptor-regulated enhancer RNAs in castration-resistant prostate cancer. Cell Reports 15: 599–610. [PMC free article: PMC5395199] [PubMed: 27068475]
    456.
    Chen H. and Liang H. (2020) A high-resolution map of human enhancer RNA loci characterizes super-enhancer activities in cancer. Cancer Cell 38: 701–715. [PMC free article: PMC7658066] [PubMed: 33007258]
    457.
    Katsushima K. et al. (2021) The long noncoding RNA lnc-HLX-2–7 is oncogenic in Group 3 medulloblastomas. Neuro-Oncology 23: 572–585. [PMC free article: PMC8041340] [PubMed: 33844835]
    458.
    Thomas H.F. et al. (2021) Temporal dissection of an enhancer cluster reveals distinct temporal and functional contributions of individual elements. Molecular Cell 81: 969 –82. [PubMed: 33482114]
    459.
    Melgar M.F., Collins F.S. and Sethupathy P. (2011) Discovery of active enhancers through bidirectional expression of short transcripts. Genome Biology 12: R113. [PMC free article: PMC3334599] [PubMed: 22082242]
    460.
    Andersson R. et al. (2014) An atlas of active enhancers across human cell types and tissues. Nature 507: 455–461. [PMC free article: PMC5215096] [PubMed: 24670763]
    461.
    Pnueli L., Rudnizky S., Yosefzon Y. and Melamed P. (2015) RNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin alpha-subunit gene. Proceedings of the National Academy of Sciences USA 112: 4369–4374. [PMC free article: PMC4394321] [PubMed: 25810254]
    462.
    Kouno T. et al. (2019) C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution. Nature Communications 10: 360. [PMC free article: PMC6341120] [PubMed: 30664627]
    463.
    Seila A.C. et al. (2008) Divergent transcription from active promoters. Science 322: 1849–1851. [PMC free article: PMC2692996] [PubMed: 19056940]
    464.
    Young R.S., Kumar Y., Bickmore W.A. and Taylor M.S. (2017) Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers. Genome Biology 18: 242. [PMC free article: PMC5747114] [PubMed: 29284524]
    465.
    Mikhaylichenko O. et al. (2018) The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription. Genes & Development 32: 42–57. [PMC free article: PMC5828394] [PubMed: 29378788]
    466.
    Pefanis E. et al. (2015) RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell 161: 774–789. [PMC free article: PMC4428671] [PubMed: 25957685]
    467.
    Tippens N.D., Vihervaara A. and Lis J.T. (2018) Enhancer transcription: What, where, when, and why? Genes & Development 32: 1–3. [PMC free article: PMC5828389] [PubMed: 29440223]
    468.
    Harman C.C.D. et al. (2021) An in vivo screen of noncoding loci reveals that Daedalus is a gatekeeper of an Ikaros-dependent checkpoint during haematopoiesis. Proceedings of the National Academy of Sciences USA 118: e1918062118. [PMC free article: PMC7826330] [PubMed: 33446502]
    469.
    Drewell R.A., Bae E., Burr J. and Lewis E.B. (2002) Transcription defines the embryonic domains of cis-regulatory activity at the Drosophila bithorax complex. Proceedings of the National Academy of Sciences USA 99: 16853–16858. [PMC free article: PMC139233] [PubMed: 12477928]
    470.
    Orom U.A. et al. (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143: 46–58. [PMC free article: PMC4108080] [PubMed: 20887892]
    471.
    Orom U.A. and Shiekhattar R. (2011) Noncoding RNAs and enhancers: Complications of a long-distance relationship. Trends in Genetics 27: 433–439. [PMC free article: PMC4484734] [PubMed: 21831473]
    472.
    Alvarez-Dominguez J.R., Knoll M., Gromatzky A.A. and Lodish H.F. (2017) The super-enhancer-derived alncRNA-EC7/Bloodlinc potentiates red blood cell development in trans. Cell Reports 19: 2503–2514. [PMC free article: PMC6013260] [PubMed: 28636939]
    473.
    Cajigas I. et al. (2018) The Evf2 ultraconserved enhancer lncRNA functionally and spatially organizes megabase distant genes in the developing forebrain. Molecular Cell 71: 956–972. [PMC free article: PMC6428050] [PubMed: 30146317]
    474.
    Tsai P.-F. et al. (2018) A muscle-specific enhancer RNA mediates cohesin recruitment and regulates transcription in trans. Molecular Cell 71: 129–141. [PMC free article: PMC6082425] [PubMed: 29979962]
    475.
    Morrison T.A. et al. (2018) A long noncoding RNA from the HBS1L-MYB intergenic region on chr6q23 regulates human fetal hemoglobin expression. Blood Cells, Molecules, and Diseases 69: 1–9. [PMC free article: PMC5783741] [PubMed: 29227829]
    476.
    Ntini E. and Marsico A. (2019) Functional impacts of non-coding RNA processing on enhancer activity and target gene expression. Journal of Molecular Cell Biology 11: 868–879. [PMC free article: PMC6884709] [PubMed: 31169884]
    477.
    Fatima R., Choudhury S.R., Divya T. R., Bhaduri U. and Rao M.R.S. (2019) A novel enhancer RNA, Hmrhl, positively regulates its host gene, phkb, in chronic myelogenous leukemia. Noncoding RNA Research 4: 96–108. [PMC free article: PMC6926186] [PubMed: 31891018]
    478.
    Yan P. et al. (2020) LncRNA Platr22 promotes super-enhancer activity and stem cell pluripotency. Journal of Molecular Cell Biology 13: 295–313. [PMC free article: PMC8339366] [PubMed: 33049031]
    479.
    Allou L. et al. (2021) Non-coding deletions identify Maenli lncRNA as a limb-specific En1 regulator. Nature 592: 93–98. [PubMed: 33568816]
    480.
    Borsari B. et al. (2021) Enhancers with tissue-specific activity are enriched in intronic regions. Genome Research 31: 1325–1336. [PMC free article: PMC8327915] [PubMed: 34290042]
    481.
    Gibcus J.H. and Dekker J. (2013) The hierarchy of the 3D genome. Molecular Cell 49: 773–782. [PMC free article: PMC3741673] [PubMed: 23473598]
    482.
    Isoda T. et al. (2017) Non-coding transcription instructs chromatin folding and compartmentalization to dictate enhancer-promoter communication and T cell fate. Cell 171: 103–119. [PMC free article: PMC5621651] [PubMed: 28938112]
    483.
    Yang Y. et al. (2016) Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster. Scientific Reports 6: 20961. [PMC free article: PMC4750091] [PubMed: 26864944]
    484.
    Benabdallah N.S. et al. (2019) Decreased enhancer-promoter proximity accompanying enhancer activation. Molecular Cell 76: 473–484. [PMC free article: PMC6838673] [PubMed: 31494034]
    485.
    Crump N.T. et al. (2021) BET inhibition disrupts transcription but retains enhancer-promoter contact. Nature Communications 12: 223. [PMC free article: PMC7801379] [PubMed: 33431820]
    486.
    Kornienko A.E., Guenzl P.M., Barlow D.P. and Pauler F.M. (2013) Gene regulation by the act of long non-coding RNA transcription. BMC Biology 11: 59. [PMC free article: PMC3668284] [PubMed: 23721193]
    487.
    de Lara J.C.-F., Arzate-Mejía R.G. and Recillas-Targa F. (2019) Enhancer RNAs: Insights into their biological role. Epigenetics Insights 12: 1–7. [PMC free article: PMC6505235] [PubMed: 31106290]
    488.
    Levine M., Cattoglio C. and Tjian R. (2014) Looping back to leap forward: Transcription enters a new era. Cell 157: 13–25. [PMC free article: PMC4059561] [PubMed: 24679523]
    489.
    Halfon M.S. (2019) Studying transcriptional enhancers: The founder fallacy, validation creep, and other biases. Trends in Genetics 35: 93–103. [PMC free article: PMC6338480] [PubMed: 30553552]
    490.
    Engreitz J.M. et al. (2016) Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature 539: 452–455. [PMC free article: PMC6853796] [PubMed: 27783602]
    491.
    Paralkar Vikram R. et al. (2016) Unlinking an lncRNA from its associated cis element. Molecular Cell 62: 104–110. [PMC free article: PMC4877494] [PubMed: 27041223]
    492.
    Kioussis D. and Festenstein R. (1997) Locus control regions: Overcoming heterochromatin-induced gene inactivation in mammals. Current Opinion in Genetics and Development 7: 614–619. [PubMed: 9388777]
    493.
    Sipos L. et al. (1998) Transvection in the Drosophila Abd-B domain: Extensive upstream sequences are involved in anchoring distant cis-regulatory regions to the promoter. Genetics 149: 1031–1050. [PMC free article: PMC1460194] [PubMed: 9611211]
    494.
    Melo C.A. et al. (2013) eRNAs are required for p53-dependent enhancer activity and gene transcription. Molecular Cell 49: 524–535. [PubMed: 23273978]
    495.
    Lam M.T.Y., Li W., Rosenfeld M.G. and Glass C.K. (2014) Enhancer RNAs and regulated transcriptional programs. Trends in Biochemical Sciences 39: 170–182. [PMC free article: PMC4266492] [PubMed: 24674738]
    496.
    Yin Y. et al. (2015) Opposing roles for the lncRNA Haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation. Cell Stem Cell 16: 504–516. [PubMed: 25891907]
    497.
    Stafford D.A., Dichmann D.S., Chang J.K. and Harland R.M. (2017) Deletion of the sclerotome-enriched lncRNA PEAT augments ribosomal protein expression. Proceedings of the National Academy of Sciences USA 114: 101–106. [PMC free article: PMC5224379] [PubMed: 27986952]
    498.
    Andergassen D. et al. (2019) The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes. PLOS Genetics 15: e1008268. [PMC free article: PMC6675118] [PubMed: 31329595]
    499.
    Bond A.M. et al. (2009) Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. Nature Neuroscience 12: 1020–1027. [PMC free article: PMC3203213] [PubMed: 19620975]
    500.
    Aguilo F. et al. (2016) Deposition of 5-methylcytosine on enhancer RNAs enables the coactivator function of PGC-1a. Cell Reports 14: 479–492. [PMC free article: PMC4731243] [PubMed: 26774474]
    501.
    Cheng J.X. et al. (2018) RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia. Nature Communications 9: 1163. [PMC free article: PMC5862959] [PubMed: 29563491]
    502.
    Tan J.Y., Biasini A., Young R.S. and Marques A.C. (2020) Splicing of enhancer-associated lincRNAs contributes to enhancer activity. Life Science Alliance 3: e202000663. [PMC free article: PMC7035876] [PubMed: 32086317]
    503.
    Maass P.G. et al. (2012) A misplaced lncRNA causes brachydactyly in humans. Journal of Clinical Investigation 122: 3990–4002. [PMC free article: PMC3485082] [PubMed: 23093776]
    504.
    Li W. et al. (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498: 516–520. [PMC free article: PMC3718886] [PubMed: 23728302]
    505.
    Xiang J.F. et al. (2014) Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Research 24: 513–531. [PMC free article: PMC4011346] [PubMed: 24662484]
    506.
    Sun J. et al. (2014) A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies. Nucleic Acids Research 42: 9588–9601. [PMC free article: PMC4150754] [PubMed: 25092925]
    507.
    Paralkar V.R. et al. (2014) Lineage and species-specific long noncoding RNAs during erythro-megakaryocytic development. Blood 123: 1927–1937. [PMC free article: PMC3962165] [PubMed: 24497530]
    508.
    Lu L. et al. (2013) Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis. EMBO journal 32: 2575–2588. [PMC free article: PMC3791367] [PubMed: 23942234]
    509.
    Shii L., Song L., Maurer K., Zhang Z. and Sullivan K.E. (2017) SERPINB2 is regulated by dynamic interactions with pause-release proteins and enhancer RNAs. Molecular Immunology 88: 20–31. [PMC free article: PMC5535806] [PubMed: 28578223]
    510.
    Han X. et al. (2019) The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression of Hand2. Development 146: dev176198. [PubMed: 31273086]
    511.
    Andergassen D. and Rinn J.L. (2021) From genotype to phenotype: Genetics of mammalian long non-coding RNAs in vivo. Nature Reviews Genetics 23: 229–243. [PubMed: 34837040]
    512.
    Rahnamoun H. et al. (2018) RNAs interact with BRD4 to promote enhanced chromatin engagement and transcription activation. Nature Structural & Molecular Biology 25: 687–697. [PMC free article: PMC6859054] [PubMed: 30076409]
    513.
    Fang K. et al. (2020) Cis-acting lnc-eRNA SEELA directly binds histone H4 to promote histone recognition and leukemia progression. Genome Biology 21: 269. [PMC free article: PMC7607629] [PubMed: 33143730]
    514.
    Groff A.F., Barutcu A.R., Lewandowski J.P. and Rinn J.L. (2018) Enhancers in the Peril lincRNA locus regulate distant but not local genes. Genome Biology 19: 219. [PMC free article: PMC6290506] [PubMed: 30537984]
    515.
    Hu T. et al. (2017) Long non-coding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function. Nucleic Acids Research 45: 4479–4492. [PMC free article: PMC5416847] [PubMed: 28132025]
    516.
    Rothschild G. et al. (2020) Noncoding RNA transcription alters chromosomal topology to promote isotype-specific class switch recombination. Science Immunology 5: eaay5864. [PMC free article: PMC7608691] [PubMed: 32034089]
    517.
    Chen H., Du G., Song X. and Li L. (2017) Non-coding transcripts from enhancers: New insights into enhancer activity and gene expression regulation. Genomics, Proteomics & Bioinformatics 15: 201–207. [PMC free article: PMC5487526] [PubMed: 28599852]
    518.
    Cai Z. et al. (2020) RIC-seq for global in situ profiling of RNA–RNA spatial interactions. Nature 582: 432–437. [PubMed: 32499643]
    519.
    Lim B. and Levine M.S. (2021) Enhancer-promoter communication: Hubs or loops? Current Opinion in Genetics & Development 67: 5–9. [PMC free article: PMC8653970] [PubMed: 33202367]
    520.
    Zhu I., Song W., Ovcharenko I. and Landsman D. (2021) A model of active transcription hubs that unifies the roles of active promoters and enhancers. Nucleic Acids Research 49: 4493–4505. [PMC free article: PMC8096258] [PubMed: 33872375]
    521.
    Mele M. and Rinn J.L. (2016) “Cat’s cradling” the 3D genome by the act of lncRNA transcription. Molecular Cell 62: 657–664. [PubMed: 27259198]
    522.
    Morf J., Basu S. and Amaral P.P. (2020) RNA, genome output and input. Frontiers in Genetics 11: 1330. [PMC free article: PMC7652816] [PubMed: 33193726]
    523.
    Berry J., Weber S.C., Vaidya N., Haataja M. and Brangwynne C.P. (2015) RNA transcription modulates phase transition-driven nuclear body assembly. Proceedings of the National Academy of Sciences USA 112: E5237–45. [PMC free article: PMC4586886] [PubMed: 26351690]
    524.
    Creamer K.M., Kolpa H.J. and Lawrence J.B. (2021) Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction. Molecular Cell 81: 3509–3525. [PMC free article: PMC8419111] [PubMed: 34320406]
    525.
    Cusanovich D.A. et al. (2018) A single-cell atlas of in vivo mammalian chromatin accessibility. Cell 174: 1309–1324. [PMC free article: PMC6158300] [PubMed: 30078704]
    526.
    Fang R. et al. (2021) Comprehensive analysis of single cell ATAC-seq data with SnapATAC. Nature Communications 12: 1337. [PMC free article: PMC7910485] [PubMed: 33637727]
    527.
    Shen Y. et al. (2012) A map of the cis-regulatory sequences in the mouse genome. Nature 488: 116–120. [PMC free article: PMC4041622] [PubMed: 22763441]
    528.
    Thurman R.E. et al. (2012) The accessible chromatin landscape of the human genome. Nature 489: 75–82. [PMC free article: PMC3721348] [PubMed: 22955617]
    529.
    The Encode Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74. [PMC free article: PMC3439153] [PubMed: 22955616]
    530.
    Zhu J. et al. (2013) Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell 152: 642–654. [PMC free article: PMC3563935] [PubMed: 23333102]
    531.
    Heidari N. et al. (2014) Genome-wide map of regulatory interactions in the human genome. Genome Research 24: 1905–1917. [PMC free article: PMC4248309] [PubMed: 25228660]
    532.
    Pott S. and Lieb J.D. (2015) What are super-enhancers? Nature Genetics 47: 8–12. [PubMed: 25547603]
    533.
    Li S. and Ovcharenko I. (2020) Enhancer jungles establish robust tissue-specific regulatory control in the human genome. Genomics 112: 2261–2270. [PMC free article: PMC7082202] [PubMed: 31887344]
    534.
    Austenaa L.M.I. et al. (2021) A first exon termination checkpoint preferentially suppresses extragenic transcription. Nature Structural & Molecular Biology 28: 337–346. [PMC free article: PMC7610630] [PubMed: 33767452]
    535.
    Gil N. and Ulitsky I. (2021) Inefficient splicing curbs noncoding RNA transcription. Nature Structural & Molecular Biology 28: 327–328. [PubMed: 33767453]
    536.
    Laffleur B. et al. (2021) Noncoding RNA processing by DIS3 regulates chromosomal architecture and somatic hypermutation in B cells. Nature Genetics 53: 230–242. [PMC free article: PMC8011275] [PubMed: 33526923]
    537.
    Anderson P. and Kedersha N. (2009) RNA granules: Post-transcriptional and epigenetic modulators of gene expression. Nature Reviews Molecular Cell Biology 10: 430–436. [PubMed: 19461665]
    538.
    Buchan J.R. (2014) mRNP granules. RNA Biology 11: 1019–1030. [PMC free article: PMC4615263] [PubMed: 25531407]
    539.
    Wright P.E. and Dyson H.J. (2015) Intrinsically disordered proteins in cellular signalling and regulation. Nature Reviews Molecular Cell Biology 16: 18–29. [PMC free article: PMC4405151] [PubMed: 25531225]
    540.
    Brangwynne C.P., Mitchison T.J. and Hyman A.A. (2011) Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proceedings of the National Academy of Sciences USA 108: 4334–4339. [PMC free article: PMC3060270] [PubMed: 21368180]
    541.
    Hyman A.A., Weber C.A. and Jülicher F. (2014) Liquid-liquid phase separation in biology. Annual Review of Cell and Developmental Biology 30: 39–58. [PubMed: 25288112]
    542.
    Polymenidou M. (2018) The RNA face of phase separation. Science 360: 859–860. [PubMed: 29798872]
    543.
    Narlikar G.J. et al. (2021) Is transcriptional regulation just going through a phase? Molecular Cell 81: 1579–1585. [PubMed: 33861943]
    544.
    Shin Y. and Brangwynne C.P. (2017) Liquid phase condensation in cell physiology and disease. Science 357: eaaf4382. [PubMed: 28935776]
    545.
    Yoshizawa T., Nozawa R.-S., Jia T.Z., Saio T. and Mori E. (2020) Biological phase separation: Cell biology meets biophysics. Biophysical Reviews 12: 519–539. [PMC free article: PMC7242575] [PubMed: 32189162]
    546.
    Lin Y., Protter D.S.W., Rosen M.K. and Parker R. (2015) Formation and maturation of phase-separated liquid droplets by RNA-binding proteins. Molecular Cell 60: 208–219. [PMC free article: PMC4609299] [PubMed: 26412307]
    547.
    Zhang H. et al. (2015) RNA controls polyQ protein phase transitions. Molecular Cell 60: 220–230. [PMC free article: PMC5221516] [PubMed: 26474065]
    548.
    Järvelin A.I., Noerenberg M., Davis I. and Castello A. (2016) The new (dis)order in RNA regulation. Cell Communication and Signaling 14: 9. [PMC free article: PMC4822317] [PubMed: 27048167]
    549.
    Fay M.M. and Anderson P.J. (2018) The role of RNA in biological phase separations. Journal of Molecular Biology 430: 4685–4701. [PMC free article: PMC6204303] [PubMed: 29753780]
    550.
    Protter D.S.W. et al. (2018) Intrinsically disordered regions can contribute promiscuous interactions to RNP granule assembly. Cell Reports 22: 1401–1412. [PMC free article: PMC5824733] [PubMed: 29425497]
    551.
    Hahn S. (2018) Phase separation, protein disorder, and enhancer function. Cell 175: 1723–1725. [PubMed: 30550782]
    552.
    Sanders D.W. et al. (2020) Competing protein-RNA interaction networks control multiphase intracellular organization. Cell 181: 306–324. [PMC free article: PMC7816278] [PubMed: 32302570]
    553.
    Roden C. and Gladfelter A.S. (2021) RNA contributions to the form and function of biomolecular condensates. Nature Reviews Molecular Cell Biology 22: 183–195. [PMC free article: PMC7785677] [PubMed: 32632317]
    554.
    Uversky V.N. (2013) A decade and a half of protein intrinsic disorder: Biology still waits for physics. Protein Science 22: 693–724. [PMC free article: PMC3690711] [PubMed: 23553817]
    555.
    Uversky V.N. (2016) Dancing protein clouds: The strange biology and chaotic physics of intrinsically disordered proteins. Journal of Biological Chemistry 291: 6681–6688. [PMC free article: PMC4807255] [PubMed: 26851286]
    556.
    Uversky V.N. (2019) Intrinsically disordered proteins and their “mysterious” (meta)physics. Frontiers in Physics 7: 10.
    557.
    Kulkarni P. and Uversky V.N. (2018) Intrinsically disordered proteins: The dark horse of the dark proteome. Proteomics 18: 1800061. [PubMed: 30218496]
    558.
    Cumberworth A., Lamour G., Babu M.M. and Gsponer J. (2013) Promiscuity as a functional trait: Intrinsically disordered regions as central players of interactomes. Biochemical Journal 454: 361–369. [PubMed: 23988124]
    559.
    Niklas K.J., Bondos S.E., Dunker A.K. and Newman S.A. (2015) Rethinking gene regulatory networks in light of alternative splicing, intrinsically disordered protein domains, and post-translational modifications. Frontiers in Cell and Developmental Biology 3: 8. [PMC free article: PMC4341551] [PubMed: 25767796]
    560.
    Niklas K.J., Dunker A.K. and Yruela I. (2018) The evolutionary origins of cell type diversification and the role of intrinsically disordered proteins. Journal of Experimental Botany 69: 1437–1446. [PubMed: 29394379]
    561.
    Macossay-Castillo M. et al. (2019) The balancing act of intrinsically disordered proteins: Enabling functional diversity while minimizing promiscuity. Journal of Molecular Biology 431: 1650–1670. [PMC free article: PMC6453724] [PubMed: 30878482]
    562.
    Ozdilek B.A. et al. (2017) Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding. Nucleic Acids Research 45: 7984–7996. [PMC free article: PMC5570134] [PubMed: 28575444]
    563.
    Balcerak A., Trebinska-Stryjewska A., Konopinski R., Wakula M. and Grzybowska E.A. (2019) RNA–protein interactions: Disorder, moonlighting and junk contribute to eukaryotic complexity. Open Biology 9: 190096. [PMC free article: PMC6597761] [PubMed: 31213136]
    564.
    Robertson N.O. et al. (2018) Disparate binding kinetics by an intrinsically disordered domain enables temporal regulation of transcriptional complex formation. Proceedings of the National Academy of Sciences USA 115: 4643–4648. [PMC free article: PMC5939062] [PubMed: 29666277]
    565.
    Peeters E., Driessen R.P.C., Werner F. and Dame R.T. (2015) The interplay between nucleoid organization and transcription in archaeal genomes. Nature Reviews Microbiology 13: 333–341. [PubMed: 25944489]
    566.
    Monterroso B. et al. (2019) Bacterial FtsZ protein forms phase-separated condensates with its nucleoid-associated inhibitor SlmA. EMBO Reports 20: e45946. [PMC free article: PMC6322363] [PubMed: 30523075]
    567.
    Ladouceur A.-M. et al. (2020) Clusters of bacterial RNA polymerase are biomolecular condensates that assemble through liquid–liquid phase separation. Proceedings of the National Academy of Sciences USA 117: 18540–18549. [PMC free article: PMC7414142] [PubMed: 32675239]
    568.
    Guilhas B. et al. (2020) ATP-driven separation of liquid phase condensates in bacteria. Molecular Cell 79: 293–303. [PubMed: 32679076]
    569.
    Niklas K.J. (2014) The evolutionary-developmental origins of multicellularity. American Journal of Botany 101: 6–25. [PubMed: 24363320]
    570.
    Korneta I. and Bujnicki J.M. (2012) Intrinsic disorder in the human spliceosomal proteome. PLOS Computational Biology 8: e1002641. [PMC free article: PMC3415423] [PubMed: 22912569]
    571.
    Tantos A., Han K.-H. and Tompa P. (2012) Intrinsic disorder in cell signaling and gene transcription. Molecular and Cellular Endocrinology 348: 457–465. [PubMed: 21782886]
    572.
    Chen W. and Moore M.J. (2014) The spliceosome: Disorder and dynamics defined. Current Opinion in Structural Biology 24: 141–149. [PMC free article: PMC3987960] [PubMed: 24530854]
    573.
    Lazar T. et al. (2016) Intrinsic protein disorder in histone lysine methylation. Biology Direct 11: 30. [PMC free article: PMC4928265] [PubMed: 27356874]
    574.
    Peng Z., Mizianty M.J., Xue B., Kurgan L. and Uversky V.N. (2012) More than just tails: Intrinsic disorder in histone proteins. Molecular BioSystems 8: 1886–1901. [PubMed: 22543956]
    575.
    Watson M. and Stott K. (2019) Disordered domains in chromatin-binding proteins. Essays in Biochemistry 63: 147–156. [PubMed: 30940742]
    576.
    Quintero-Cadena P., Lenstra T.L. and Sternberg P.W. (2020) RNA Pol II length and disorder enable cooperative scaling of transcriptional bursting. Molecular Cell 79: 207–220. [PubMed: 32544389]
    577.
    Musselman C.A. and Kutateladze T.G. (2021) Characterization of functional disordered regions within chromatin-associated proteins. iScience 24: 102070. [PMC free article: PMC7873657] [PubMed: 33604523]
    578.
    Romero P.R. et al. (2006) Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms. Proceedings of the National Academy of Sciences USA 103: 8390–8395. [PMC free article: PMC1482503] [PubMed: 16717195]
    579.
    Buljan M. et al. (2012) Tissue-specific splicing of disordered segments that embed binding motifs rewires protein interaction networks. Molecular Cell 46: 871–883. [PMC free article: PMC3437557] [PubMed: 22749400]
    580.
    Ellis J.D. et al. (2012) Tissue-specific alternative splicing remodels protein-protein interaction networks. Molecular Cell 46: 884–892. [PubMed: 22749401]
    581.
    Barbosa-Morais N.L. et al. (2012) The evolutionary landscape of alternative splicing in vertebrate species. Science 338: 1587–1593. [PubMed: 23258890]
    582.
    Gueroussov S. et al. (2017) Regulatory expansion in mammals of multivalent hnRNP assemblies that globally control alternative splicing. Cell 170: 324–339. [PubMed: 28709000]
    583.
    Weatheritt R.J., Davey N.E. and Gibson T.J. (2012) Linear motifs confer functional diversity onto splice variants. Nucleic Acids Research 40: 7123–7131. [PMC free article: PMC3424572] [PubMed: 22638587]
    584.
    Weatheritt R.J. and Gibson T.J. (2012) Linear motifs: Lost in (pre)translation. Trends in Biochemical Sciences 37: 333–341. [PubMed: 22705166]
    585.
    Guillén-Boixet J. et al. (2020) RNA-Induced conformational switching and clustering of G3BP drive stress granule assembly by condensation. Cell 181: 346–361. [PMC free article: PMC7181197] [PubMed: 32302572]
    586.
    Meyer K. et al. (2018) Mutations in disordered regions can cause disease by creating dileucine motifs. Cell 175: 239–253. [PubMed: 30197081]
    587.
    Pechstein A. et al. (2020) Vesicle clustering in a living synapse depends on a synapsin region that mediates phase separation. Cell Reports 30: 2594–2602. [PubMed: 32101738]
    588.
    Iakoucheva L.M. et al. (2004) The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Research 32: 1037–1049. [PMC free article: PMC373391] [PubMed: 14960716]
    589.
    Pejaver V. et al. (2014) The structural and functional signatures of proteins that undergo multiple events of post-translational modification. Protein Science 23: 1077–1093. [PMC free article: PMC4116656] [PubMed: 24888500]
    590.
    Bah A. and Forman-Kay J.D. (2016) Modulation of intrinsically disordered protein function by post-translational modifications. Journal of Biological Chemistry 291: 6696–6705. [PMC free article: PMC4807257] [PubMed: 26851279]
    591.
    Wei H.-M. et al. (2014) Arginine methylation of the cellular nucleic acid binding protein does not affect its subcellular localization but impedes RNA binding. FEBS Letters 588: 1542–1548. [PubMed: 24726729]
    592.
    Nott T.J. et al. (2015) Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Molecular Cell 57: 936–947. [PMC free article: PMC4352761] [PubMed: 25747659]
    593.
    Castello A. et al. (2016) Comprehensive identification of RNA-binding domains in human cells. Molecular Cell 63: 696–710. [PMC free article: PMC5003815] [PubMed: 27453046]
    594.
    Chong P.A., Vernon R.M. and Forman-Kay J.D. (2018) RGG/RG motif regions in RNA binding and phase separation. Journal of Molecular Biology 430: 4650–4665. [PubMed: 29913160]
    595.
    Wesseling H. et al. (2020) Tau PTM profiles identify patient heterogeneity and stages of Alzheimer’s Disease. Cell 183: 1699–1713. [PMC free article: PMC8168922] [PubMed: 33188775]
    596.
    Loughlin F.E. et al. (2021) Tandem RNA binding sites induce self-association of the stress granule marker protein TIA-1. Nucleic Acids Research 49: 2403–2417. [PMC free article: PMC7969032] [PubMed: 33621982]
    597.
    Apicco D.J. et al. (2018) Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo. Nature Neuroscience 21: 72–80. [PMC free article: PMC5745051] [PubMed: 29273772]
    598.
    White M.R. et al. (2019) C9orf72 poly(PR) dipeptide repeats disturb biomolecular phase separation and disrupt nucleolar function. Molecular Cell 74: 713–728. [PMC free article: PMC6525025] [PubMed: 30981631]
    599.
    Kim T.H. et al. (2019) Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates regulation of translation and deadenylation. Science 365: 825–829. [PubMed: 31439799]
    600.
    Loganathan S., Lehmkuhl E.M., Eck R.J. and Zarnescu D.C. (2020) To be or not to be…toxic — is RNA association with TDP-43 complexes deleterious or protective in neurodegeneration? Frontiers in Molecular Biosciences 6: 154. [PMC free article: PMC6965497] [PubMed: 31998750]
    601.
    Yu H. et al. (2021) HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science 371: eabb4309. [PMC free article: PMC8286096] [PubMed: 33335017]
    602.
    Bakthavachalu B. et al. (2018) RNP-granule assembly via ataxin-2 disordered domains is required for long-term memory and neurodegeneration. Neuron 98: 754–766. [PubMed: 29772202]
    603.
    Gonatopoulos-Pournatzis T. et al. (2020) Autism-misregulated eIF4G microexons control synaptic translation and higher order cognitive functions. Molecular Cell 77: 1176–1192. [PubMed: 31999954]
    604.
    Gsponer J., Futschik M.E., Teichmann S.A. and Babu M.M. (2008) Tight regulation of unstructured proteins: From transcript synthesis to protein degradation. Science 322: 1365–1368. [PMC free article: PMC2803065] [PubMed: 19039133]
    605.
    Vavouri T., Semple J.I., Garcia-Verdugo R. and Lehner B. (2009) Intrinsic protein disorder and interaction promiscuity are widely associated with dosage sensitivity. Cell 138: 198–208. [PubMed: 19596244]
    606.
    Jain A. and Vale R.D. (2017) RNA phase transitions in repeat expansion disorders. Nature 546: 243–247. [PMC free article: PMC5555642] [PubMed: 28562589]
    607.
    Ray S. et al. (2020) α-Synuclein aggregation nucleates through liquid–liquid phase separation. Nature Chemistry 12: 705–716. [PubMed: 32514159]
    608.
    Castello A., Fischer B., Hentze M.W. and Preiss T. (2013) RNA-binding proteins in Mendelian disease. Trends in Genetics 29: 318–327. [PubMed: 23415593]
    609.
    Strom A.R. et al. (2017) Phase separation drives heterochromatin domain formation. Nature 547: 241–245. [PMC free article: PMC6022742] [PubMed: 28636597]
    610.
    Hnisz D., Shrinivas K., Young R.A., Chakraborty A.K. and Sharp P.A. (2017) A phase separation model for transcriptional control. Cell 169: 13–23. [PMC free article: PMC5432200] [PubMed: 28340338]
    611.
    Garcia-Jove Navarro M. et al. (2019) RNA is a critical element for the sizing and the composition of phase-separated RNA–protein condensates. Nature Communications 10: 3230. [PMC free article: PMC6642089] [PubMed: 31324804]
    612.
    Frank L. and Rippe K. (2020) Repetitive RNAs as regulators of chromatin-associated subcompartment formation by phase separation. Journal of Molecular Biology 432: 4270–4286. [PubMed: 32320688]
    613.
    Jacq A. et al. (2021) Direct RNA–RNA interaction between Neat1 and RNA targets, as a mechanism for RNAs paraspeckle retention. RNA Biology 18: 1–12. [PMC free article: PMC8583173] [PubMed: 33573434]
    614.
    Quinodoz S.A. et al. (2021) RNA promotes the formation of spatial compartments in the nucleus. Cell 184: 5775–5790. [PMC free article: PMC9115877] [PubMed: 34739832]
    615.
    Courchaine E.M., Lu A. and Neugebauer K.M. (2016) Droplet organelles? EMBO Journal 35: 1603–1612. [PMC free article: PMC4969579] [PubMed: 27357569]
    616.
    Parker M.W. et al. (2019) A new class of disordered elements controls DNA replication through initiator self-assembly. eLife 8: e48562. [PMC free article: PMC6764820] [PubMed: 31560342]
    617.
    Zhang H. et al. (2020) Nuclear body phase separation drives telomere clustering in ALT cancer cells. Molecular Biology of the Cell 31: 2048–2056. [PMC free article: PMC7543070] [PubMed: 32579423]
    618.
    Zwicker D., Decker M., Jaensch S., Hyman A.A. and Jülicher F. (2014) Centrosomes are autocatalytic droplets of pericentriolar material organized by centrioles. Proceedings of the National Academy of Sciences USA 111: E2636–45. [PMC free article: PMC4084434] [PubMed: 24979791]
    619.
    Shimada T., Yamashita A. and Yamamoto M. (2003) The fission yeast meiotic regulator Mei2p forms a dot structure in the horse-tail nucleus in association with the sme2 locus on chromosome II. Molecular Biology of the Cell 14: 2461–2469. [PMC free article: PMC194894] [PubMed: 12808043]
    620.
    Hiraoka Y. (2020) Phase separation drives pairing of homologous chromosomes. Current Genetics 66: 881–887. [PubMed: 32285141]
    621.
    Kistler K.E. et al. (2018) Phase transitioned nuclear Oskar promotes cell division of Drosophila primordial germ cells. eLife 7: e37949. [PMC free article: PMC6191285] [PubMed: 30260314]
    622.
    Trinkle-Mulcahy L. and Sleeman J.E. (2017) The Cajal body and the nucleolus: “In a relationship” or “It’s complicated”? RNA Biology 14: 739–751. [PMC free article: PMC5519233] [PubMed: 27661468]
    623.
    Hur W. et al. (2020) CDK-regulated phase separation seeded by histone genes ensures precise growth and function of histone locus bodies. Developmental Cell 54: 379–394. [PMC free article: PMC7423771] [PubMed: 32579968]
    624.
    Yamazaki T. and Hirose T. (2021) Control of condensates dictates nucleolar architecture. Science 373: 486–487. [PubMed: 34326220]
    625.
    Alexander K.A. et al. (2021) p53 mediates target gene association with nuclear speckles for amplified RNA expression. Molecular Cell 81: 1666–1681. [PMC free article: PMC8830378] [PubMed: 33823140]
    626.
    Liu S. et al. (2021) USP42 drives nuclear speckle mRNA splicing via directing dynamic phase separation to promote tumorigenesis. Cell Death & Differentiation 28: 2482–2498. [PMC free article: PMC8329168] [PubMed: 33731873]
    627.
    Sone M. et al. (2007) The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons. Journal of Cell Science 120: 2498–2506. [PubMed: 17623775]
    628.
    Ishizuka A., Hasegawa Y., Ishida K., Yanaka K. and Nakagawa S. (2014) Formation of nuclear bodies by the lncRNA Gomafu-associating proteins Celf3 and SF1. Genes to Cells 19: 704–721. [PMC free article: PMC4255692] [PubMed: 25145264]
    629.
    Tripathi V. et al. (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Molecular Cell 39: 925–938. [PMC free article: PMC4158944] [PubMed: 20797886]
    630.
    Sasaki Y.T., Ideue T., Sano M., Mituyama T. and Hirose T. (2009) MEN epsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proceedings of the National Academy of Sciences USA 106: 2525–2530. [PMC free article: PMC2650297] [PubMed: 19188602]
    631.
    Fox A.H., Nakagawa S., Hirose T. and Bond C.S. (2018) Paraspeckles: Where long noncoding RNA meets phase separation. Trends in Biochemical Sciences 43: 124–135. [PubMed: 29289458]
    632.
    Fox A.H. et al. (2002) Paraspeckles: A novel nuclear domain. Current Biology 12: 13–25. [PubMed: 11790299]
    633.
    Yamazaki T. et al. (2018) Functional domains of NEAT1 architectural lncRNA induce paraspeckle assembly through phase separation. Molecular Cell 70: 1038–1053. [PubMed: 29932899]
    634.
    Yamazaki T. et al. (2021) Paraspeckles are constructed as block copolymer micelles. The EMBO Journal 40: e107270. [PMC free article: PMC8204865] [PubMed: 33885174]
    635.
    Keenen M.M. et al. (2021) HP1 proteins compact DNA into mechanically and positionally stable phase separated domains. eLife 10: e64563. [PMC free article: PMC7932698] [PubMed: 33661100]
    636.
    Biamonti G. and Vourc’h C. (2010) Nuclear stress bodies. Cold Spring Harbor Perspectives in Biology 2: a000695. [PMC free article: PMC2869524] [PubMed: 20516127]
    637.
    Ninomiya K. et al. (2020) LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation. EMBO Journal 39: e102729. [PMC free article: PMC6996502] [PubMed: 31782550]
    638.
    Stortz M., Pecci A., Presman D.M. and Levi V. (2020) Unraveling the molecular interactions involved in phase separation of glucocorticoid receptor. BMC Biology 18: 59. [PMC free article: PMC7268505] [PubMed: 32487073]
    639.
    Chen H. et al. (2020) Liquid–liquid phase separation by SARS-CoV-2 nucleocapsid protein and RNA. Cell Research 30: 1143–1145. [PMC free article: PMC7477871] [PubMed: 32901111]
    640.
    Emenecker R.J., Holehouse A.S. and Strader L.C. (2020) Emerging roles for phase separation in plants. Developmental Cell 55: 69–83. [PMC free article: PMC7577370] [PubMed: 33049212]
    641.
    Anderson P. and Kedersha N. (2006) RNA granules. Journal of Cell Biology 172: 803–808. [PMC free article: PMC2063724] [PubMed: 16520386]
    642.
    Mateu-Regué À., Nielsen F.C. and Christiansen J. (2020) Cytoplasmic mRNPs revisited: Singletons and condensates. BioEssays 42: 2000097. [PubMed: 33145808]
    643.
    Brangwynne C.P. et al. (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324: 1729–1732. [PubMed: 19460965]
    644.
    Smith J. et al. (2016) Spatial patterning of P granules by RNA-induced phase separation of the intrinsically-disordered protein MEG-3. eLife 5: e21337. [PMC free article: PMC5262379] [PubMed: 27914198]
    645.
    Jin M. et al. (2017) Glycolytic enzymes coalesce in G bodies under hypoxic stress. Cell Reports 20: 895–908. [PMC free article: PMC5586494] [PubMed: 28746874]
    646.
    Molliex A. et al. (2015) Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163: 123–133. [PMC free article: PMC5149108] [PubMed: 26406374]
    647.
    Nakamura A., Amikura R., Mukai M., Kobayashi S. and Lasko P.F. (1996) Requirement for a noncoding RNA in Drosophila polar granules for germ cell establishment. Science 274: 2075–2079. [PubMed: 8953037]
    648.
    Sankaranarayanan M. and Weil T.T. (2020) Granule regulation by phase separation during Drosophila oogenesis. Emerging Topics in Life Sciences 4: 355–364. [PMC free article: PMC7733668] [PubMed: 32573699]
    649.
    Weatheritt R.J., Gibson T.J. and Babu M.M. (2014) Asymmetric mRNA localization contributes to fidelity and sensitivity of spatially localized systems. Nature Structural & Molecular Biology 21: 833–839. [PMC free article: PMC4167633] [PubMed: 25150862]
    650.
    Chouaib R. et al. (2020) A dual protein-mRNA localization screen reveals compartmentalized translation and widespread co-translational RNA targeting. Developmental Cell 54: 773–791. [PubMed: 32783880]
    651.
    Chen X., Wu X., Wu H. and Zhang M. (2020) Phase separation at the synapse. Nature Neuroscience 23: 301–310. [PubMed: 32015539]
    652.
    Mao Y.S., Sunwoo H., Zhang B. and Spector D.L. (2011) Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nature Cell Biology 13: 95–101. [PMC free article: PMC3007124] [PubMed: 21170033]
    653.
    Henninger J.E. et al. (2021) RNA-mediated feedback control of transcriptional condensates. Cell 184: 207–225. [PMC free article: PMC8128340] [PubMed: 33333019]
    654.
    Luo J. et al. (2021) LncRNAs: Architectural scaffolds or more potential roles in phase separation. Frontiers in Genetics 12: 369. [PMC free article: PMC8044363] [PubMed: 33868368]
    655.
    Quinodoz S.A. and Guttman M. (2021) Essential roles for RNA in shaping nuclear organization. Cold Spring Harbor Perspectives in Biology. epub ahead of print: https:​//cshperspectives​.cshlp.org/content​/early/2021/08/16/cshperspect​.a039719.long. [PMC free article: PMC9159268] [PubMed: 34400555]
    656.
    Klosin A. et al. (2020) Phase separation provides a mechanism to reduce noise in cells. Science 367: 464–468. [PubMed: 31974256]
    657.
    Ahn J.H. et al. (2021) Phase separation drives aberrant chromatin looping and cancer development. Nature 595: 591–595. [PMC free article: PMC8647409] [PubMed: 34163069]
    658.
    Sabari B.R. et al. (2018) Coactivator condensation at super-enhancers links phase separation and gene control. Science 361: eaar3958. [PMC free article: PMC6092193] [PubMed: 29930091]
    659.
    Nair S.J. et al. (2019) Phase separation of ligand-activated enhancers licenses cooperative chromosomal enhancer assembly. Nature Structural & Molecular Biology 26: 193–203. [PMC free article: PMC6709854] [PubMed: 30833784]
    660.
    Shrinivas K. et al. (2019) Enhancer features that drive formation of transcriptional condensates. Molecular Cell 75: 549–561. [PMC free article: PMC6690378] [PubMed: 31398323]
    661.
    Boija A. et al. (2018) Transcription factors activate genes through the phase-separation capacity of their activation domains. Cell 175: 1842–1855. [PMC free article: PMC6295254] [PubMed: 30449618]
    662.
    Chong S. et al. (2018) Imaging dynamic and selective low-complexity domain interactions that control gene transcription. Science 361: eaar2555. [PMC free article: PMC6961784] [PubMed: 29930090]
    663.
    Cho W.-K. et al. (2018) Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science 361: 412–415. [PMC free article: PMC6543815] [PubMed: 29930094]
    664.
    Shao W. et al. (2022) Phase separation of RNA-binding protein promotes polymerase binding and transcription. Nature Chemical Biology 18: 70–80. [PubMed: 34916619]
    665.
    Falk M. et al. (2019) Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature 570: 395–399. [PMC free article: PMC7206897] [PubMed: 31168090]
    666.
    Rawal C.C., Caridi C.P. and Chiolo I. (2019) Actin’ between phase separated domains for heterochromatin repair. DNA Repair 81: 102646. [PMC free article: PMC6764897] [PubMed: 31522911]
    667.
    Hofmann J.W., Seeley W.W. and Huang E.J. (2019) RNA binding proteins and the pathogenesis of frontotemporal lobar degeneration. Annual Review of Pathology: Mechanisms of Disease 14: 469–495. [PMC free article: PMC6731550] [PubMed: 30355151]
    668.
    Williams J.F. et al. (2020) Phase separation enables heterochromatin domains to do mechanical work. bioRxiv: 2020.07.02.184127.
    669.
    Novo C.L. et al. (2020) Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells. bioRxiv: 2020.06.08.139642. [PMC free article: PMC9209518] [PubMed: 35725842]
    670.
    Hilbert L. et al. (2021) Transcription organizes euchromatin via microphase separation. Nature Communications 12: 1360. [PMC free article: PMC7921102] [PubMed: 33649325]
    671.
    Caudron-Herger M. et al. (2015) Alu element-containing RNAs maintain nucleolar structure and function. EMBO Journal 34: 2758–2774. [PMC free article: PMC4682651] [PubMed: 26464461]
    672.
    Xing Y.-H. et al. (2017) SLERT regulates DDX21 rings associated with Pol I transcription. Cell 169: 664–678. [PubMed: 28475895]
    673.
    Wang X. et al. (2021) Mutual dependency between lncRNA LETN and protein NPM1 in controlling the nucleolar structure and functions sustaining cell proliferation. Cell Research 31: 664–683. [PMC free article: PMC8169757] [PubMed: 33432115]
    674.
    Wu M. et al. (2021) lncRNA SLERT controls phase separation of FC/DFCs to facilitate Pol I transcription. Science 373: 547–555. [PubMed: 34326237]
    675.
    Yap K. et al. (2018) A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival. Molecular Cell 72: 525–540. [PMC free article: PMC6224606] [PubMed: 30318443]
    676.
    Pessina F. et al. (2019) Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors. Nature Cell Biology 21: 1286–1299. [PMC free article: PMC6859070] [PubMed: 31570834]
    677.
    Pessina F. et al. (2021) DNA damage triggers a new phase in neurodegeneration. Trends in Genetics 37: 337–354. [PubMed: 33020022]
    678.
    Thapar R. et al. (2020) Mechanism of efficient double-strand break repair by a long non-coding RNA. Nucleic Acids Research 48: 10953–10972. [PMC free article: PMC7641761] [PubMed: 33045735]
    679.
    Cabili M.N. et al. (2015) Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution. Genome Biology 16: 20. [PMC free article: PMC4369099] [PubMed: 25630241]
    680.
    Goldstrohm A.C., Hall T.M.T. and McKenney K.M. (2018) Post-transcriptional regulatory functions of mammalian Pumilio proteins. Trends in Genetics 34: 972–990. [PMC free article: PMC6251728] [PubMed: 30316580]
    681.
    Tichon A. et al. (2016) A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells. Nature Communications 7: 12209. [PMC free article: PMC4947167] [PubMed: 27406171]
    682.
    Lee S. et al. (2016) Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins. Cell 164: 69–80. [PMC free article: PMC4715682] [PubMed: 26724866]
    683.
    Tichon A., Perry R.B.-T., Stojic L. and Ulitsky I. (2018) SAM68 is required for regulation of Pumilio by the NORAD long noncoding RNA. Genes & Development 32: 70–78. [PMC free article: PMC5828396] [PubMed: 29386330]
    684.
    Elguindy M.M. and Mendell J.T. (2021) NORAD-induced Pumilio phase separation is required for genome stability. Nature 595: 303–308. [PMC free article: PMC8266761] [PubMed: 34108682]
    685.
    Kopp F. et al. (2019) PUMILIO hyperactivity drives premature aging of Norad-deficient mice. eLife 8: e42650. [PMC free article: PMC6407921] [PubMed: 30735131]
    686.
    Brecht R.M. et al. (2020) Nucleolar localization of RAG1 modulates V(D)J recombination activity. Proceedings of the National Academy of Sciences USA 117: 4300–4309. [PMC free article: PMC7049140] [PubMed: 32047031]
    687.
    Simone R. et al. (2021) MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration. Nature 594: 117–123. [PMC free article: PMC7610982] [PubMed: 34012113]
    688.
    Amé J.-C., Spenlehauer C. and de Murcia G. (2004) The PARP superfamily. BioEssays 26: 882–893. [PubMed: 15273990]
    689.
    Citarelli M., Teotia S. and Lamb R.S. (2010) Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes. BMC Evolutionary Biology 10: 308. [PMC free article: PMC2964712] [PubMed: 20942953]
    690.
    Ray Chaudhuri A. and Nussenzweig A. (2017) The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nature Reviews Molecular Cell Biology 18: 610–621. [PMC free article: PMC6591728] [PubMed: 28676700]
    691.
    Höfer K. et al. (2021) Viral ADP-ribosyltransferases attach RNA chains to host proteins. bioRxiv: 446905.
    692.
    Guetg C., Scheifele F., Rosenthal F., Hottiger M.O. and Santoro R. (2012) Inheritance of silent rDNA chromatin is mediated by PARP1 via noncoding RNA. Molecular Cell 45: 790–800. [PubMed: 22405650]
    693.
    Qi H. et al. (2018) The long noncoding RNA lncPARP1 contributes to progression of hepatocellular carcinoma through up-regulation of PARP1. Bioscience Reports 38: BSR20180703. [PMC free article: PMC6013699] [PubMed: 29776974]
    694.
    Wang Y., Zhou P., Li P., Yang F. and Gao X.-Q. (2020) Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1. Bioengineered 11: 536–546. [PMC free article: PMC8291873] [PubMed: 32345117]
    695.
    Stapleton K. et al. (2020) Novel long noncoding RNA, macrophage inflammation-suppressing transcript (MIST), regulates macrophage activation during obesity. Arteriosclerosis, Thrombosis, and Vascular Biology 40: 914–928. [PMC free article: PMC7098442] [PubMed: 32078363]
    696.
    Melikishvili M., Chariker J.H., Rouchka E.C. and Fondufe-Mittendorf Y.N. (2017) Transcriptome-wide identification of the RNA-binding landscape of the chromatin-associated protein PARP1 reveals functions in RNA biogenesis. Cell Discovery 3: 17043. [PMC free article: PMC5787697] [PubMed: 29387452]
    697.
    Ke Y., Zhang J., Lv X., Zeng X. and Ba X. (2019) Novel insights into PARPs in gene expression: Regulation of RNA metabolism. Cellular and Molecular Life Sciences 76: 3283–3299. [PMC free article: PMC6697709] [PubMed: 31055645]
    698.
    Altmeyer M. et al. (2015) Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). Nature Communications 6: 8088. [PMC free article: PMC4560800] [PubMed: 26286827]
    699.
    Duan Y. et al. (2019) PARylation regulates stress granule dynamics, phase separation, and neurotoxicity of disease-related RNA-binding proteins. Cell Research 29: 233–247. [PMC free article: PMC6460439] [PubMed: 30728452]
    700.
    Murakami K., Oshimura M. and Kugoh H. (2007) Suggestive evidence for chromosomal localization of non-coding RNA from imprinted LIT1. Journal of Human Genetics 52: 926–933. [PubMed: 17917697]
    701.
    Royo H. et al. (2007) Bsr, a nuclear-retained RNA with monoallelic expression. Molecular Biology of the Cell 18: 2817–2827. [PMC free article: PMC1949380] [PubMed: 17507654]
    702.
    Alessio E. et al. (2019) Single cell analysis reveals the involvement of the long non-coding RNA Pvt1 in the modulation of muscle atrophy and mitochondrial network. Nucleic Acids Research 47: 1653–1670. [PMC free article: PMC6393313] [PubMed: 30649422]
    703.
    Jonkhout N. et al. (2021) Subcellular relocalization and nuclear redistribution of the RNA methyltransferases TRMT1 and TRMT1L upon neuronal activation. RNA Biology 18: 1905–1919. [PMC free article: PMC8583002] [PubMed: 33499731]
    704.
    de Laat W. and Grosveld F. (2003) Spatial organization of gene expression: The active chromatin hub. Chromosome Research 11: 447–459. [PubMed: 12971721]
    705.
    Poudyal R.R., Pir Cakmak F., Keating C.D. and Bevilacqua P.C. (2018) Physical principles and extant biology reveal roles for RNA-containing membraneless compartments in origins of life chemistry. Biochemistry 57: 2509–2519. [PMC free article: PMC7276092] [PubMed: 29560725]
    706.
    Strulson C.A., Molden R.C., Keating C.D. and Bevilacqua P.C. (2012) RNA catalysis through compartmentalization. Nature Chemistry 4: 941–946. [PubMed: 23089870]
    707.
    Drobot B. et al. (2018) Compartmentalised RNA catalysis in membrane-free coacervate protocells. Nature Communications 9: 3643. [PMC free article: PMC6128941] [PubMed: 30194374]
    708.
    Blanco C., Bayas M., Yan F. and Chen I.A. (2018) Analysis of evolutionarily independent protein-RNA complexes yields a criterion to evaluate the relevance of prebiotic scenarios. Current Biology 28: 526–537. [PubMed: 29398222]
    709.
    Son A., Horowitz S. and Seong B.L. (2021) Chaperna: Linking the ancient RNA and protein worlds. RNA Biology 18: 16–23. [PMC free article: PMC7834078] [PubMed: 32781880]
    710.
    Deveson I.W. et al. (2018) Universal alternative splicing of noncoding exons. Cell Systems 6: 245–255. [PubMed: 29396323]
    711.
    Furuno M. et al. (2006) Clusters of internally primed transcripts reveal novel long noncoding RNAs. PLOS Genetics 2: e37. [PMC free article: PMC1449886] [PubMed: 16683026]
    712.
    Koziol M.J. and Rinn J.L. (2010) RNA traffic control of chromatin complexes. Current Opinion in Genetics and Development 20: 142–148. [PMC free article: PMC2895502] [PubMed: 20362426]
    713.
    Guttman M. and Rinn J.L. (2012) Modular regulatory principles of large non-coding RNAs. Nature 482: 339–346. [PMC free article: PMC4197003] [PubMed: 22337053]
    714.
    Mercer T.R. and Mattick J.S. (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nature Structural & Molecular Biology 20: 300–307. [PubMed: 23463315]
    715.
    Ross C.J. et al. (2021) Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences. Genome Biology 22: 29. [PMC free article: PMC7798263] [PubMed: 33430943]
    716.
    Smith M.A., Gesell T., Stadler P.F. and Mattick J.S. (2013) Widespread purifying selection on RNA structure in mammals. Nucleic Acids Research 41: 8220–8236. [PMC free article: PMC3783177] [PubMed: 23847102]
    717.
    Uroda T. et al. (2019) Conserved pseudoknots in lncRNA MEG3 are essential for stimulation of the p53 pathway. Molecular Cell 75: 982–995. [PMC free article: PMC6739425] [PubMed: 31444106]
    718.
    Smith M.A., Seemann S.E., Quek X.C. and Mattick J.S. (2017) DotAligner: Identification and clustering of RNA structure motifs. Genome Biology 18: 244. [PMC free article: PMC5747123] [PubMed: 29284541]
    719.
    Seemann S.E. et al. (2017) The identification and functional annotation of RNA structures conserved in vertebrates. Genome Research 27: 1371–1383. [PMC free article: PMC5538553] [PubMed: 28487280]
    720.
    Miladi M. et al. (2017) RNAscClust: Clustering RNA sequences using structure conservation and graph based motifs. Bioinformatics 33: 2089–2096. [PMC free article: PMC5870858] [PubMed: 28334186]
    721.
    Johnson R. and Guigo R. (2014) The RIDL hypothesis: Transposable elements as functional domains of long noncoding RNAs. RNA 20: 959–976. [PMC free article: PMC4114693] [PubMed: 24850885]
    722.
    Nesterova T.B. et al. (2001) Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence. Genome Research 11: 833–849. [PMC free article: PMC311126] [PubMed: 11337478]
    723.
    Sprague D. et al. (2019) Nonlinear sequence similarity between the Xist and Rsx long noncoding RNAs suggests shared functions of tandem repeat domains. RNA 25: 1004–1019. [PMC free article: PMC6633197] [PubMed: 31097619]
    724.
    Quinn J.J. et al. (2016) Rapid evolutionary turnover underlies conserved lncRNA-genome interactions. Genes & Development 30: 191–207. [PMC free article: PMC4719309] [PubMed: 26773003]
    725.
    Alfeghaly C. et al. (2021) Implication of repeat insertion domains in the trans-activity of the long non-coding RNA ANRIL. Nucleic Acids Research 49: 4954–4970. [PMC free article: PMC8136789] [PubMed: 33872355]
    726.
    Kelley D.R., Hendrickson D.G., Tenen D. and Rinn J.L. (2014) Transposable elements modulate human RNA abundance and splicing via specific RNA-protein interactions. Genome Biology 15: 537. [PMC free article: PMC4272801] [PubMed: 25572935]
    727.
    Ilik I.A. et al. (2013) Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila. Molecular Cell 51: 156–173. [PMC free article: PMC3804161] [PubMed: 23870142]
    728.
    Kapusta A. et al. (2013) Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLOS Genetics 9: e1003470. [PMC free article: PMC3636048] [PubMed: 23637635]
    729.
    McClintock M.A. et al. (2018) RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs. eLife 7: e36312. [PMC free article: PMC6056234] [PubMed: 29944118]
    730.
    Somarowthu S. et al. (2015) HOTAIR forms an intricate and modular secondary structure. Molecular Cell 58: 353–361. [PMC free article: PMC4406478] [PubMed: 25866246]
    731.
    Spitale R.C. et al. (2015) Structural imprints in vivo decode RNA regulatory mechanisms. Nature 519: 486–490. [PMC free article: PMC4376618] [PubMed: 25799993]
    732.
    Chowdhury I.H. et al. (2017) Expression profiling of long noncoding RNA splice variants in human microvascular endothelial cells: Lipopolysaccharide effects in vitro. Mediators of Inflammation 2017: 3427461. [PMC free article: PMC5632992] [PubMed: 29147069]
    733.
    Kiegle E.A., Garden A., Lacchini E. and Kater M.M. (2018) A genomic view of alternative splicing of long non-coding RNAs during rice seed development reveals extensive splicing and lncRNAgene families. Frontiers in Plant Science 9: 115. [PMC free article: PMC5808331] [PubMed: 29467783]
    734.
    Ma X. et al. (2019) Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers. Frontiers of Medicine 13: 330–343. [PubMed: 29808251]
    735.
    Khan M.R., Wellinger R.J. and Laurent B. (2021) Exploring the alternative splicing of long noncoding RNAs. Trends in Genetics 37: 695–698. [PubMed: 33892960]
    736.
    Li P., Tao Z. and Dean C. (2015) Phenotypic evolution through variation in splicing of the noncoding RNA COOLAIR. Genes & Development 29: 696–701. [PMC free article: PMC4387712] [PubMed: 25805848]
    737.
    Wu H. et al. (2016) Unusual processing generates SPA LncRNAs that sequester multiple RNA binding proteins. Molecular Cell 64: 534–548. [PubMed: 27871485]
    738.
    Guo C.-J. et al. (2020) Distinct processing of lncRNAs contributes to non-conserved functions in stem cells. Cell 181: 621–636. [PubMed: 32259487]
    739.
    Rauzan B. et al. (2013) Kinetics and thermodynamics of DNA, RNA, and hybrid duplex formation. Biochemistry 52: 765–772. [PubMed: 23356429]
    740.
    Zhou J. et al. (2015) H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase. Nature Communications 6: 10221. [PMC free article: PMC4703905] [PubMed: 26687445]
    741.
    Mercer T.R. et al. (2013) DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements. Nature Genetics 45: 852–859. [PMC free article: PMC4405174] [PubMed: 23793028]
    742.
    Torarinsson E. et al. (2008) Comparative genomics beyond sequence-based alignments: RNA structures in the ENCODE regions. Genome Research 18: 242–251. [PMC free article: PMC2203622] [PubMed: 18096747]
    743.
    Will S., Yu M. and Berger B. (2013) Structure-based whole genome realignment reveals many novel non-coding RNAs. Genome Research 23: 1018–1027. [PMC free article: PMC3668356] [PubMed: 23296921]
    744.
    Miao Z. et al. (2015) RNA-Puzzles Round II: Assessment of RNA structure prediction programs applied to three large RNA structures. RNA 21: 1066–1084. [PMC free article: PMC4436661] [PubMed: 25883046]
    745.
    Vandivier L.E., Anderson S.J., Foley S.W. and Gregory B.D. (2016) The conservation and function of RNA secondary structure in plants. Annual Review of Plant Biology 67: 463–488. [PMC free article: PMC5125251] [PubMed: 26865341]
    746.
    Zhao Q. et al. (2021) Review of machine learning methods for RNA secondary structure prediction. PLOS Computational Biology 17: e1009291. [PMC free article: PMC8389396] [PubMed: 34437528]
    747.
    Townshend R.J.L. et al. (2021) Geometric deep learning of RNA structure. Science 373: 1047–1051. [PMC free article: PMC9829186] [PubMed: 34446608]
    748.
    Licatalosi D.D. et al. (2008) HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456: 464–469. [PMC free article: PMC2597294] [PubMed: 18978773]
    749.
    Hafner M. et al. (2010) Transcriptome-wide Identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141: 129–141. [PMC free article: PMC2861495] [PubMed: 20371350]
    750.
    König J. et al. (2010) iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nature Structural & Molecular Biology 17: 909–915. [PMC free article: PMC3000544] [PubMed: 20601959]
    751.
    Zarnegar B.J. et al. (2016) irCLIP platform for efficient characterization of protein-RNA interactions. Nature Methods 13: 489–492. [PMC free article: PMC5477425] [PubMed: 27111506]
    752.
    McFadden E.J. and Hargrove A.E. (2016) Biochemical methods to investigate lncRNA and the influence of lncRNA: Protein complexes on chromatin. Biochemistry 55: 1615–1630. [PMC free article: PMC5010801] [PubMed: 26859437]
    753.
    Bridges M.C., Daulagala A.C. and Kourtidis A. (2021) LNCcation: lncRNA localization and function. Journal of Cell Biology 220: e202009045. [PMC free article: PMC7816648] [PubMed: 33464299]
    754.
    Fan Y. et al. (2021) Genome-wide detection and quantitation of RNA distribution by ChIRC13a-seq. Protocol Exchange. Online publication: https:​//protocolexchange​.researchsquare.com​/article/pex–1416/v1.
    755.
    Van Nostrand E.L. et al. (2020) A large-scale binding and functional map of human RNA-binding proteins. Nature 583: 711–719. [PMC free article: PMC7410833] [PubMed: 32728246]
    756.
    Kalvari I. et al. (2018) Rfam 13.0: Shifting to a genome-centric resource for non-coding RNA families. Nucleic Acids Research 46: D335–42. [PMC free article: PMC5753348] [PubMed: 29112718]
    757.
    El-Gebali S. et al. (2019) The Pfam protein families database in 2019. Nucleic Acids Research 47: D427–32. [PMC free article: PMC6324024] [PubMed: 30357350]
    758.
    Taft R.J., Pheasant M. and Mattick J.S. (2007) The relationship between non-protein-coding DNA and eukaryotic complexity. BioEssays 29: 288–299. [PubMed: 17295292]
    759.
    Liu G., Mattick J.S. and Taft R.J. (2013) A meta-analysis of the genomic and transcriptomic composition of complex life. Cell Cycle 12: 2061–2072. [PMC free article: PMC3737309] [PubMed: 23759593]

    Chapter 17

    1.
    D‘Alessandro A. et al. (2016) AltitudeOmics: Red blood cell metabolic adaptation to high altitude hypoxia. Journal of Proteome Research 15: 3883–3895. [PMC free article: PMC5512539] [PubMed: 27646145]
    2.
    Julian C.G. (2017) Epigenomics and human adaptation to high altitude. Journal of Applied Physiology 123: 1362–1370. [PMC free article: PMC6157641] [PubMed: 28819001]
    3.
    Childebayeva A. et al. (2019) DNA methylation changes are associated with an incremental ascent to high altitude. Frontiers in Genetics 10: 1062. [PMC free article: PMC6828981] [PubMed: 31737045]
    4.
    Ling C. and Rönn T. (2019) Epigenetics in human obesity and type 2 diabetes. Cell Metabolism 29: 1028–1044. [PMC free article: PMC6509280] [PubMed: 30982733]
    5.
    Khera A.V. et al. (2018) Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nature Genetics 50: 1219–1224. [PMC free article: PMC6128408] [PubMed: 30104762]
    6.
    Christensen B.C. et al. (2009) Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLOS Genetics 5: e1000602. [PMC free article: PMC2718614] [PubMed: 19680444]
    7.
    Day J.J. and Sweatt J.D. (2011) Cognitive neuroepigenetics: A role for epigenetic mechanisms in learning and memory. Neurobiology of Learning and Memory 96: 2–12. [PMC free article: PMC3111867] [PubMed: 21195202]
    8.
    Martin E.M. and Fry R.C. (2018) Environmental influences on the epigenome: Exposure- associated DNA methylation in human populations. Annual Review of Public Health 39: 309–333. [PubMed: 29328878]
    9.
    Kim S. and Kaang B.-K. (2017) Epigenetic regulation and chromatin remodeling in learning and memory. Experimental & Molecular Medicine 49: e281. [PMC free article: PMC5291841] [PubMed: 28082740]
    10.
    Collins B.E., Greer C.B., Coleman B.C. and Sweatt J.D. (2019) Histone H3 lysine K4 methylation and its role in learning and memory. Epigenetics & Chromatin 12: 7. [PMC free article: PMC6322263] [PubMed: 30616667]
    11.
    Mattick J.S., Amaral P.P., Dinger M.E., Mercer T.R. and Mehler M.F. (2009) RNA regulation of epigenetic processes. BioEssays 31: 51–59. [PubMed: 19154003]
    12.
    Mattick J.S. (2010) RNA as the substrate for epigenome-environment interactions. BioEssays 32: 548–552. [PubMed: 20544741]
    13.
    Dias B.G., Maddox S., Klengel T. and Ressler K.J. (2015) Epigenetic mechanisms underlying learning and the inheritance of learned behaviors. Trends in Neuroscience 38: 96–107. [PMC free article: PMC4323865] [PubMed: 25544352]
    14.
    Duempelmann L., Skribbe M. and Bühler M. (2020) Small RNAs in the transgenerational inheritance of epigenetic information. Trends in Genetics 36: 203–214. [PubMed: 31952840]
    15.
    Ramanathan A., Robb G.B. and Chan S.-H. (2016) mRNA capping: Biological functions and applications. Nucleic Acids Research 44: 7511–7526. [PMC free article: PMC5027499] [PubMed: 27317694]
    16.
    Galloway A. and Cowling V.H. (2019) mRNA cap regulation in mammalian cell function and fate. Biochimica et Biophysica Acta 1862: 270–279. [PMC free article: PMC6414751] [PubMed: 30312682]
    17.
    Wang J. et al. (2019) Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA. Nucleic Acids Research 47: e130. [PMC free article: PMC6847653] [PubMed: 31504804]
    18.
    Bird J.G. et al. (2016) The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA. Nature 535: 444–447. [PMC free article: PMC4961592] [PubMed: 27383794]
    19.
    Jonkhout N. et al. (2017) The RNA modification landscape in human disease. RNA 23: 1754–1769. [PMC free article: PMC5688997] [PubMed: 28855326]
    20.
    Roundtree I.A., Evans M.E., Pan T. and He C. (2017) Dynamic RNA modifications in gene expression regulation. Cell 169: 1187–1200. [PMC free article: PMC5657247] [PubMed: 28622506]
    21.
    Boccaletto P. et al. (2018) MODOMICS: A database of RNA modification pathways. 2017 update. Nucleic Acids Research 46: D303–7. [PMC free article: PMC5753262] [PubMed: 29106616]
    22.
    Behrens A., Rodschinka G. and Nedialkova D.D. (2021) High-resolution quantitative profiling of tRNA abundance and modification status in eukaryotes by mim-tRNAseq. Molecular Cell 81: 1802–1815. [PMC free article: PMC8062790] [PubMed: 33581077]
    23.
    Wolk S.K. et al. (2020) Modified nucleotides may have enhanced early RNA catalysis. Proceedings of the National Academy of Sciences USA 117: 8236–8242. [PMC free article: PMC7165471] [PubMed: 32229566]
    24.
    Sloan K.E. et al. (2017) Tuning the ribosome: The influence of rRNA modification on eukaryotic ribosome biogenesis and function. RNA Biology 14: 1138–1152. [PMC free article: PMC5699541] [PubMed: 27911188]
    25.
    Dominissini D. et al. (2012) Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485: 201–206. [PubMed: 22575960]
    26.
    Meyer K.D. et al. (2012) Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149: 1635–1646. [PMC free article: PMC3383396] [PubMed: 22608085]
    27.
    Squires J.E. et al. (2012) Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Research 40: 5023–5033. [PMC free article: PMC3367185] [PubMed: 22344696]
    28.
    Hussain S. et al. (2013) NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Reports 4: 255–261. [PMC free article: PMC3730056] [PubMed: 23871666]
    29.
    Khoddami V. and Cairns B.R. (2013) Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nature Biotechnology 31: 458–464. [PMC free article: PMC3791587] [PubMed: 23604283]
    30.
    Carlile T.M. et al. (2014) Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 515: 143–146. [PMC free article: PMC4224642] [PubMed: 25192136]
    31.
    Schwartz S. et al. (2014) Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159: 148–162. [PMC free article: PMC4180118] [PubMed: 25219674]
    32.
    Schwartz S. et al. (2014) Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5′ sites. Cell Reports 8: 284 –96. [PMC free article: PMC4142486] [PubMed: 24981863]
    33.
    Dominissini D. et al. (2016) The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA. Nature 530: 441–446. [PMC free article: PMC4842015] [PubMed: 26863196]
    34.
    Alarcon C.R., Lee H., Goodarzi H., Halberg N. and Tavazoie S.F. (2015) N6-methyladenosine marks primary microRNAs for processing. Nature 519: 482–485. [PMC free article: PMC4475635] [PubMed: 25799998]
    35.
    Esteller M. and Pandolfi P.P. (2017) The epitranscriptome of noncoding RNAs in cancer. Cancer Discovery 7: 359–368. [PMC free article: PMC5997407] [PubMed: 28320778]
    36.
    Bohnsack K.E., Höbartner C. and Bohnsack M.T. (2019) Eukaryotic 5-methylcytosine (m5C) RNA methyltransferases: Mechanisms, cellular functions, and links to disease. Genes 10: 102. [PMC free article: PMC6409601] [PubMed: 30704115]
    37.
    Adachi H., De Zoysa M.D. and Yu Y.-T. (2019) Post-transcriptional pseudouridylation in mRNA as well as in some major types of noncoding RNAs. Biochimica et Biophysica Acta 1862: 230–239. [PMC free article: PMC6401265] [PubMed: 30414851]
    38.
    Jia G. et al. (2011) N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nature Chemical Biology 7: 885–887. [PMC free article: PMC3218240] [PubMed: 22002720]
    39.
    Zhao X. et al. (2014) FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Research 24: 1403–1419. [PMC free article: PMC4260349] [PubMed: 25412662]
    40.
    Liu F. et al. (2016) ALKBH1-mediated tRNA demethylation regulates translation. Cell 167: 816–828. [PMC free article: PMC5119773] [PubMed: 27745969]
    41.
    Saletore Y. et al. (2012) The birth of the Epitranscriptome: Deciphering the function of RNA modifications. Genome Biology 13: 175. [PMC free article: PMC3491402] [PubMed: 23113984]
    42.
    Novoa E.M., Mason C.E. and Mattick J.S. (2017) Charting the unknown epitranscriptome. Nature Reviews Molecular Cell Biology 18: 339–340. [PubMed: 28488699]
    43.
    Linder B. et al. (2015) Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nature Methods 12: 767–772. [PMC free article: PMC4487409] [PubMed: 26121403]
    44.
    Batista P.J. et al. (2014) m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15: 707–719. [PMC free article: PMC4278749] [PubMed: 25456834]
    45.
    Li S. and Mason C.E. (2014) The pivotal regulatory landscape of RNA modifications. Annual Review of Genomics and Human Genetics 15: 127–150. [PubMed: 24898039]
    46.
    Trixl L. and Lusser A. (2019) The dynamic RNA modification 5-methylcytosine and its emerging role as an epitranscriptomic mark. WIREs RNA 10: e1510. [PMC free article: PMC6492194] [PubMed: 30311405]
    47.
    Mikutis S. et al. (2020) meCLICK-Seq, a substrate-hijacking and RNA degradation strategy for the study of RNA methylation. ACS Central Science 6: 2196–2208. [PMC free article: PMC7760485] [PubMed: 33376781]
    48.
    Alarcón C.R. et al. (2015) HNRNPA2B1 Is a mediator of m6A-dependent nuclear RNA processing events. Cell 162: 1299–1308. [PMC free article: PMC4673968] [PubMed: 26321680]
    49.
    Fustin J.-M. et al. (2013) RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell 155: 793–806. [PubMed: 24209618]
    50.
    Zheng G. et al. (2013) ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Molecular Cell 49: 18–29. [PMC free article: PMC3646334] [PubMed: 23177736]
    51.
    Wang X. et al. (2014) N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505: 117–120. [PMC free article: PMC3877715] [PubMed: 24284625]
    52.
    Wang Y. et al. (2014) N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nature Cell Biology 16: 191–198. [PMC free article: PMC4640932] [PubMed: 24394384]
    53.
    Wang X. et al. (2015) N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell 161: 1388–1399. [PMC free article: PMC4825696] [PubMed: 26046440]
    54.
    Geula S. et al. (2015) m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation. Science 347: 1002–1006. [PubMed: 25569111]
    55.
    Knuckles P. et al. (2017) RNA fate determination through cotranscriptional adenosine methylation and microprocessor binding. Nature Structural & Molecular Biology 24: 561–569. [PubMed: 28581511]
    56.
    Tang C. et al. (2018) ALKBH5-dependent m6A demethylation controls splicing and stability of long 3′-UTR mRNAs in male germ cells. Proceedings of the National Academy of Sciences USA 115: E325–33. [PMC free article: PMC5777073] [PubMed: 29279410]
    57.
    Kasowitz S.D. et al. (2018) Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development. PLOS Genetics 14: e1007412. [PMC free article: PMC5991768] [PubMed: 29799838]
    58.
    Louloupi A., Ntini E., Conrad T. and Ørom U.A.V. (2018) Transient N-6-methyladenosine transcriptome sequencing reveals a regulatory role of m6A in splicing efficiency. Cell Reports 23: 3429–3437. [PubMed: 29924987]
    59.
    Zaccara S., Ries R.J. and Jaffrey S.R. (2019) Reading, writing and erasing mRNA methylation. Nature Reviews Molecular Cell Biology 20: 608–624. [PubMed: 31520073]
    60.
    Liu N. et al. (2015) N6-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 518: 560–564. [PMC free article: PMC4355918] [PubMed: 25719671]
    61.
    Spitale R.C. et al. (2015) Structural imprints in vivo decode RNA regulatory mechanisms. Nature 519: 486–490. [PMC free article: PMC4376618] [PubMed: 25799993]
    62.
    Mendel M. et al. (2021) Splice site m6A methylation prevents binding of U2AF35 to inhibit RNA splicing. Cell 184: 3125–3142. [PMC free article: PMC8208822] [PubMed: 33930289]
    63.
    Yang X. et al. (2019) m6A promotes R-loop formation to facilitate transcription termination. Cell Research 29: 1035–1038. [PMC free article: PMC6951339] [PubMed: 31606733]
    64.
    Liu J. et al. (2020) N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367: 580–586. [PMC free article: PMC7213019] [PubMed: 31949099]
    65.
    Ries R.J. et al. (2019) m6A enhances the phase separation potential of mRNA. Nature 571: 424–428. [PMC free article: PMC6662915] [PubMed: 31292544]
    66.
    Abakir A. et al. (2020) N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nature Genetics 52: 48–55. [PMC free article: PMC6974403] [PubMed: 31844323]
    67.
    Zhang C. et al. (2020) METTL3 and N6-methyladenosine promote homologous recombination-mediated repair of DSBs by modulating DNA-RNA hybrid accumulation. Molecular Cell 79: 425–442. [PubMed: 32615088]
    68.
    Wei J. and He C. (2021) Chromatin and transcriptional regulation by reversible RNA methylation. Current Opinion in Cell Biology 70: 109–115. [PMC free article: PMC8119380] [PubMed: 33706173]
    69.
    Kan R.L., Chen J. and Sallam T. (2021) Crosstalk between epitranscriptomic and epigenetic mechanisms in gene regulation. Trends in Genetics 38: 182–193. [PMC free article: PMC9093201] [PubMed: 34294427]
    70.
    Schwartz S. et al. (2013) High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell 155: 1409–1421. [PMC free article: PMC3956118] [PubMed: 24269006]
    71.
    Chelmicki T. et al. (2021) m6A RNA methylation regulates the fate of endogenous retroviruses. Nature 591: 312–316. [PubMed: 33442060]
    72.
    Xu W. et al. (2021) METTL3 regulates heterochromatin in mouse embryonic stem cells. Nature 591: 317–321. [PubMed: 33505026]
    73.
    Chen C. et al. (2021) Nuclear m6A reader Ythdc1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos. Protein & Cell 12: 455–474. [PMC free article: PMC8160034] [PubMed: 33886094]
    74.
    Duda K.J. et al. (2021) m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin. Nucleic Acids Research 49: 5568–5587. [PMC free article: PMC8191757] [PubMed: 33999208]
    75.
    Blanco S. et al. (2011) The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLOS Genetics 7: e1002403. [PMC free article: PMC3228827] [PubMed: 22144916]
    76.
    Frye M. and Blanco S. (2016) Post-transcriptional modifications in development and stem cells. Development 143: 3871–3881. [PubMed: 27803056]
    77.
    Frye M., Harada B.T., Behm M. and He C. (2018) RNA modifications modulate gene expression during development. Science 361: 1346–1349. [PMC free article: PMC6436390] [PubMed: 30262497]
    78.
    Wang Y. et al. (2018) N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nature Neuroscience 21: 195–206. [PMC free article: PMC6317335] [PubMed: 29335608]
    79.
    Hongay C.F. and Orr-Weaver T.L. (2011) Drosophila Inducer of MEiosis 4 (IME4) is required for Notch signaling during oogenesis. Proceedings of the National Academy of Sciences USA 108: 14855–14860. [PMC free article: PMC3169142] [PubMed: 21873203]
    80.
    Lin Z. and Tong M.-H. (2019) m6A mRNA modification regulates mammalian spermatogenesis. Biochimica et Biophysica Acta 1862: 403–411. [PubMed: 30391644]
    81.
    Sánchez-Vásquez E., Alata Jimenez N., Vázquez N.A. and Strobl-Mazzulla P.H. (2018) Emerging role of dynamic RNA modifications during animal development. Mechanisms of Development 154: 24–32. [PubMed: 29654887]
    82.
    Mendel M. et al. (2018) Methylation of structured RNA by the m6A writer METTL16 Is essential for mouse embryonic development. Molecular Cell 71: 986–1000. [PMC free article: PMC6162343] [PubMed: 30197299]
    83.
    Fustin J.-M. et al. (2018) Two Ck1 transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock. Proceedings of the National Academy of Sciences USA 115: 5980–5985. [PMC free article: PMC6003373] [PubMed: 29784786]
    84.
    Zhong X. et al. (2018) Circadian clock regulation of hepatic lipid metabolism by modulation of m6A mRNA methylation. Cell Reports 25: 1816–1828. [PMC free article: PMC6532766] [PubMed: 30428350]
    85.
    Schaefer M. et al. (2010) RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes & Development 24: 1590–1595. [PMC free article: PMC2912555] [PubMed: 20679393]
    86.
    Zhou J. et al. (2018) N6-methyladenosine guides mRNA alternative translation during integrated stress response. Molecular Cell 69: 636–647. [PMC free article: PMC5816726] [PubMed: 29429926]
    87.
    Alriquet M. et al. (2020) The protective role of m1A during stress-induced granulation. Journal of Molecular Cell Biology 12: 870–880. [PMC free article: PMC7883823] [PubMed: 32462207]
    88.
    Vu L.P. et al. (2017) The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nature Medicine 23: 1369–1376. [PMC free article: PMC5677536] [PubMed: 28920958]
    89.
    Wang Y.-N., Yu C.-Y. and Jin H.-Z. (2020) RNA N6-methyladenosine modifications and the immune response. Journal of Immunology Research 2020: 6327614. [PMC free article: PMC7204177] [PubMed: 32411802]
    90.
    Wu C. et al. (2020) Interplay of m6A and H3K27 trimethylation restrains inflammation during bacterial infection. Science Advances 6: eaba0647. [PMC free article: PMC7438091] [PubMed: 32875102]
    91.
    Li S.-X., Yan W., Liu J.-P., Zhao Y.-J. and Chen L. (2021) Long noncoding RNA SNHG4 remits lipopolysaccharide-engendered inflammatory lung damage by inhibiting METTL3 – Mediated m6A level of STAT2 mRNA. Molecular Immunology 139: 10–22. [PubMed: 34450538]
    92.
    Nair L. et al. (2021) Mechanism of noncoding RNA-associated N6-methyladenosine recognition by an RNA processing complex during IgH DNA recombination. Molecular Cell 81: 3949–3964. [PMC free article: PMC8571800] [PubMed: 34450044]
    93.
    Yoon K.J. et al. (2017) Temporal control of mammalian cortical neurogenesis by m6A methylation. Cell 171: 877–889. [PMC free article: PMC5679435] [PubMed: 28965759]
    94.
    Li L. et al. (2017) Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis. Human Molecular Genetics 26: 2398–2411. [PMC free article: PMC6192412] [PubMed: 28398475]
    95.
    Weng Y.-L. et al. (2018) Epitranscriptomic m6A regulation of axon regeneration in the adult mammalian nervous system. Neuron 97: 313–325. [PMC free article: PMC5777326] [PubMed: 29346752]
    96.
    Flores J.V. et al. (2017) Cytosine-5 RNA methylation regulates neural stem cell differentiation and motility. Stem Cell Reports 8: 112–124. [PMC free article: PMC5233436] [PubMed: 28041877]
    97.
    Wu R. et al. (2019) A novel m6A reader Prrc2a controls oligodendroglial specification and myelination. Cell Research 29: 23–41. [PMC free article: PMC6318280] [PubMed: 30514900]
    98.
    Hess M.E. et al. (2013) The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nature Neuroscience 16: 1042–1048. [PubMed: 23817550]
    99.
    Merkurjev D. et al. (2018) Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts. Nature Neuroscience 21: 1004–1014. [PubMed: 29950670]
    100.
    Hussain S. and Bashir Z.I. (2015) The epitranscriptome in modulating spatiotemporal RNA translation in neuronal post-synaptic function. Frontiers in Cellular Neuroscience 9: 420. [PMC free article: PMC4628113] [PubMed: 26582006]
    101.
    Yu J. et al. (2018) Dynamic m6A modification regulates local translation of mRNA in axons. Nucleic Acids Research 46: 1412–1423. [PMC free article: PMC5815124] [PubMed: 29186567]
    102.
    Ma C. et al. (2018) RNA m6A methylation participates in regulation of postnatal development of the mouse cerebellum. Genome Biology 19: 68. [PMC free article: PMC5984455] [PubMed: 29855379]
    103.
    Wang C.-X. et al. (2018) METTL3-mediated m6A modification is required for cerebellar development. PLOS Biology 16: e2004880. [PMC free article: PMC6021109] [PubMed: 29879109]
    104.
    Widagdo J. et al. (2016) Experience-dependent accumulation of N-methyladenosine in the prefrontal cortex is associated with memory processes in mice. Journal of Neuroscience 36: 6771–6777. [PMC free article: PMC4916251] [PubMed: 27335407]
    105.
    Walters B.J. et al. (2017) The role of the RNA demethylase FTO (fat mass and obesity-associated) and mRNA methylation in hippocampal memory formation. Neuropsychopharmacology 42: 1502–1510. [PMC free article: PMC5436121] [PubMed: 28205605]
    106.
    Koranda J.L. et al. (2018) Mettl14 Is essential for epitranscriptomic regulation of striatal function and learning. Neuron 99: 283–292. [PMC free article: PMC6082022] [PubMed: 30056831]
    107.
    Engel M. et al. (2018) The role of m6A/m-RNA methylation in stress response regulation. Neuron 99: 389–403. [PMC free article: PMC6069762] [PubMed: 30048615]
    108.
    Zhang Z. et al. (2018) METTL3-mediated N6- methyladenosine mRNA modification enhances long-term memory consolidation. Cell Research 28: 1050–1061. [PMC free article: PMC6218447] [PubMed: 30297870]
    109.
    Shi H. et al. (2018) m6A facilitates hippocampus-dependent learning and memory through YTHDF1. Nature 563: 249–253. [PMC free article: PMC6226095] [PubMed: 30401835]
    110.
    Xu Y. et al. (2020) Regulation of N6-methyladenosine in the differentiation of cancer stem cells and their fate. Frontiers in Cell and Developmental Biology 8: 950. [PMC free article: PMC7536555] [PubMed: 33072746]
    111.
    Haussmann I.U. et al. (2016) m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature 540: 301–304. [PubMed: 27919081]
    112.
    Lence T. et al. (2016) m6A modulates neuronal functions and sex determination in Drosophila. Nature 540: 242–247. [PubMed: 27919077]
    113.
    Kan L. et al. (2017) The m6A pathway facilitates sex determination in Drosophila. Nature Communications 8: 15737. [PMC free article: PMC5500889] [PubMed: 28675155]
    114.
    Yu Q. et al. (2021) RNA demethylation increases the yield and biomass of rice and potato plants in field trials. Nature Biotechnology 39: 1581–1588. [PubMed: 34294912]
    115.
    Xiao S. et al. (2019) The RNA N6-methyladenosine modification landscape of human fetal tissues. Nature Cell Biology 21: 651–661. [PubMed: 31036937]
    116.
    Zhou K.I. et al. (2016) N(6)-methyladenosine modification in a long noncoding RNA hairpin predisposes its conformation to protein binding. Journal of Molecular Biology 428: 822–833. [PMC free article: PMC4779075] [PubMed: 26343757]
    117.
    Wang X. et al. (2021) N6-methyladenosine modification of MALAT1 promotes metastasis via reshaping nuclear speckles. Developmental Cell 56: 702–715. [PubMed: 33609462]
    118.
    Patil D.P. et al. (2016) m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537: 369–373. [PMC free article: PMC5509218] [PubMed: 27602518]
    119.
    Yoneda R., Ueda N., Uranishi K., Hirasaki M. and Kurokawa R. (2020) Long noncoding RNA pncRNA-D reduces cyclin D1 gene expression and arrests cell cycle through RNA m6A modification. Journal of Biological Chemistry 295: 5626–5639. [PMC free article: PMC7186179] [PubMed: 32165496]
    120.
    Xhemalce B., Robson S.C. and Kouzarides T. (2012) Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell 151: 278–288. [PMC free article: PMC3640255] [PubMed: 23063121]
    121.
    Blanco S. et al. (2014) Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO Journal 33: 2020–2039. [PMC free article: PMC4195770] [PubMed: 25063673]
    122.
    Shi H., Chai P., Jia R. and Fan X. (2020) Novel insight into the regulatory roles of diverse RNA modifications: Re-defining the bridge between transcription and translation. Molecular Cancer 19: 78. [PMC free article: PMC7164178] [PubMed: 32303268]
    123.
    Mauer J. et al. (2017) Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature 541: 371–375. [PMC free article: PMC5513158] [PubMed: 28002401]
    124.
    Cheng J.X. et al. (2018) RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia. Nature Communications 9: 1163. [PMC free article: PMC5862959] [PubMed: 29563491]
    125.
    Schumann U. et al. (2020) Multiple links between 5-methylcytosine content of mRNA and translation. BMC Biology 18: 40. [PMC free article: PMC7158060] [PubMed: 32293435]
    126.
    Ali A.T., Idaghdour Y. and Hodgkinson A. (2020) Analysis of mitochondrial m1A/G RNA modification reveals links to nuclear genetic variants and associated disease processes. Communications Biology 3: 147. [PMC free article: PMC7101319] [PubMed: 32221480]
    127.
    Zhao X. et al. (2004) Regulation of nuclear receptor activity by a pseudouridine synthase through posttranscriptional modification of steroid receptor RNA activator. Molecular Cell 15: 549–558. [PubMed: 15327771]
    128.
    Liu W. et al. (2013) Brd4 and JMJD6-associated anti-pause enhancers in regulation of transcriptional pause release. Cell 155: 1581–1595. [PMC free article: PMC3886918] [PubMed: 24360279]
    129.
    Zhao Y., Karijolich J., Glaunsinger B. and Zhou Q. (2016) Pseudouridylation of 7SK snRNA promotes 7SK snRNP formation to suppress HIV-1 transcription and escape from latency. EMBO Reports 17: 1441–1451. [PMC free article: PMC5048380] [PubMed: 27558685]
    130.
    Barbieri I. and Kouzarides T. (2020) Role of RNA modifications in cancer. Nature Reviews Cancer 20: 303–322. [PubMed: 32300195]
    131.
    Chen S., Zhou L. and Wang Y. (2020) ALKBH5-mediated m6A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma. Cancer Cell International 20: 34. [PMC free article: PMC6993345] [PubMed: 32021563]
    132.
    Miano V., Codino A., Pandolfini L. and Barbieri I. (2021) The non-coding epitranscriptome in cancer. Briefings in Functional Genomics 20: 94–105. [PMC free article: PMC8479548] [PubMed: 33564819]
    133.
    Begik O. et al. (2020) Integrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures. Genome Biology 21: 97. [PMC free article: PMC7204298] [PubMed: 32375858]
    134.
    Liu J. et al. (2014) A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nature Chemical Biology 10: 93–95. [PMC free article: PMC3911877] [PubMed: 24316715]
    135.
    Meyer K.D. and Jaffrey S.R. (2017) Rethinking m6A readers, writers, and erasers. Annual Review of Cell and Developmental Biology 33: 319–342. [PMC free article: PMC5963928] [PubMed: 28759256]
    136.
    Pendleton K.E. et al. (2017) The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell 169: 824–835. [PMC free article: PMC5502809] [PubMed: 28525753]
    137.
    Chi L. and Delgado-Olguín P. (2013) Expression of NOL1/NOP2/sun domain (Nsun) RNA methyltransferase family genes in early mouse embryogenesis. Gene Expression Patterns 13: 319–327. [PubMed: 23816522]
    138.
    Heissenberger C. et al. (2019) Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth. Nucleic Acids Research 47: 11807–11825. [PMC free article: PMC7145617] [PubMed: 31722427]
    139.
    Chen P., Zhang T., Yuan Z., Shen B. and Chen L. (2019) Expression of the RNA methyltransferase Nsun5 is essential for developing cerebral cortex. Molecular Brain 12: 74. [PMC free article: PMC6714381] [PubMed: 31462248]
    140.
    Haag S. et al. (2015) NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. RNA (New York, N.Y.) 21: 1532–1543. [PMC free article: PMC4536315] [PubMed: 26160102]
    141.
    Selmi T. et al. (2020) Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6. Nucleic Acids Research 49: 1006–1022. [PMC free article: PMC7826283] [PubMed: 33330931]
    142.
    Jonkhout N. et al. (2021) Subcellular relocalization and nuclear redistribution of the RNA methyltransferases TRMT1 and TRMT1L upon neuronal activation. RNA Biology 18: 1905–1919. [PMC free article: PMC8583002] [PubMed: 33499731]
    143.
    Hauenschild R. et al. (2015) The reverse transcription signature of N-1-methyladenosine in RNA-Seq is sequence dependent. Nucleic Acids Research 43: 9950–9964. [PMC free article: PMC4787781] [PubMed: 26365242]
    144.
    Brinkerhoff H., Kang A.S.W., Liu J., Aksimentiev A. and Dekker C. (2021) Multiple rereads of single proteins at single-amino acid resolution using nanopores. Science 374: 1509–1513. [PMC free article: PMC8811723] [PubMed: 34735217]
    145.
    Bošković F. and Keyser U.F. (2021) Toward single-molecule proteomics. Science 374: 1443–1444. [PubMed: 34914497]
    146.
    Garalde D.R. et al. (2018) Highly parallel direct RNA sequencing on an array of nanopores. Nature Methods 15: 201–206. [PubMed: 29334379]
    147.
    Smith A.M., Jain M., Mulroney L., Garalde D.R. and Akeson M. (2019) Reading canonical and modified nucleobases in 16S ribosomal RNA using nanopore native RNA sequencing. PLOS ONE 14: e0216709. [PMC free article: PMC6522004] [PubMed: 31095620]
    148.
    Liu H. et al. (2019) Accurate detection of m6A RNA modifications in native RNA sequences. Nature Communications 10: 4079. [PMC free article: PMC6734003] [PubMed: 31501426]
    149.
    Workman R.E. et al. (2019) Nanopore native RNA sequencing of a human poly(A) transcriptome. Nature Methods 16: 1297–1305. [PMC free article: PMC7768885] [PubMed: 31740818]
    150.
    Leger A. et al. (2021) RNA modifications detection by comparative Nanopore direct RNA sequencing. Nature Communications 12: 7198. [PMC free article: PMC8664944] [PubMed: 34893601]
    151.
    Karikó K. et al. (2008) Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular Therapy 16: 1833–1840. [PMC free article: PMC2775451] [PubMed: 18797453]
    152.
    Karikó K., Buckstein M., Ni H. and Weissman D. (2005) Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23: 165–175. [PubMed: 16111635]
    153.
    Linares-Fernández S., Lacroix C., Exposito J.-Y. and Verrier B. (2020) Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends in Molecular Medicine 26: 311–323. [PubMed: 31699497]
    154.
    Pardi N., Hogan M.J., Porter F.W. and Weissman D. (2018) mRNA vaccines — a new era in vaccinology. Nature Reviews Drug Discovery 17: 261–279. [PMC free article: PMC5906799] [PubMed: 29326426]
    155.
    Krienke C. et al. (2021) A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science 371: 145–153. [PubMed: 33414215]
    156.
    Wardell C.M. and Levings M.K. (2021) mRNA vaccines take on immune tolerance. Nature Biotechnology 39: 419–421. [PubMed: 33785909]
    157.
    Zangi L. et al. (2013) Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction. Nature Biotechnology 31: 898–907. [PMC free article: PMC4058317] [PubMed: 24013197]
    158.
    Collén A. et al. (2022) VEGFA mRNA for regenerative treatment of heart failure. Nature Reviews Drug Discovery 21: 79–80. [PMC free article: PMC8646349] [PubMed: 34873303]
    159.
    Hou X., Zaks T., Langer R. and Dong Y. (2021) Lipid nanoparticles for mRNA delivery. Nature Reviews Materials 6: 1078–1094. [PMC free article: PMC8353930] [PubMed: 34394960]
    160.
    Winkle M., El-Daly S.M., Fabbri M. and Calin G.A. (2021) Noncoding RNA therapeutics — challenges and potential solutions. Nature Reviews Drug Discovery 20: 629–651. [PMC free article: PMC8212082] [PubMed: 34145432]
    161.
    Sletten A.C. et al. (2021) Loss of SNORA73 reprograms cellular metabolism and protects against steatohepatitis. Nature Communications 12: 5214. [PMC free article: PMC8410784] [PubMed: 34471131]
    162.
    Li Y. et al. (2021) A noncoding RNA modulator potentiates phenylalanine metabolism in mice. Science 373: 662–673. [PMC free article: PMC9714245] [PubMed: 34353949]
    163.
    Wei H. et al. (2021) Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis. Cell Reports 34: 108721. [PMC free article: PMC7920574] [PubMed: 33535036]
    164.
    Benne R. et al. (1986) Major transcript of the frameshifted coxll gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell 46: 819–826. [PubMed: 3019552]
    165.
    Blum B., Bakalara N. and Simpson L. (1990) A model for RNA editing in kinetoplastid mitochondria: “guide” RNA molecules transcribed from maxicircle DNA provide the edited information. Cell 60: 189–198. [PubMed: 1688737]
    166.
    Simpson L., Sbicego S. and Aphasizhev R. (2003) Uridine insertion/deletion RNA editing in trypanosome mitochondria: A complex business. RNA 9: 265–276. [PMC free article: PMC1370392] [PubMed: 12591999]
    167.
    Paz N. et al. (2007) Altered adenosine-to-inosine RNA editing in human cancer. Genome Research 17: 1586–1595. [PMC free article: PMC2045141] [PubMed: 17908822]
    168.
    Nishikura K. (2015) A-to-I editing of coding and non-coding RNAs by ADARs. Nature Reviews Molecular Cell Biology 17: 83–96. [PMC free article: PMC4824625] [PubMed: 26648264]
    169.
    Paz-Yaacov N. et al. (2015) Elevated RNA editing activity is a major contributor to transcriptomic diversity in tumors. Cell Reports 13: 267–276. [PubMed: 26440895]
    170.
    Kung C.-P., Maggi L.B. and Weber J.D. (2018) The role of RNA editing in cancer development and metabolic disorders. Frontiers in Endocrinology 9: 762. [PMC free article: PMC6305585] [PubMed: 30619092]
    171.
    Ishizuka J.J. et al. (2019) Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade. Nature 565: 43–48. [PMC free article: PMC7241251] [PubMed: 30559380]
    172.
    Bass B.L. and Weintraub H. (1988) An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55: 1089–1098. [PubMed: 3203381]
    173.
    Kimelman D. and Kirschner M.W. (1989) An antisense mRNA directs the covalent modification of the transcript encoding fibroblast growth factor in Xenopus oocytes. Cell 59: 687–696. [PubMed: 2479482]
    174.
    Bass B.L., Weintraub H., Cattaneo R. and Billeter M.A. (1989) Biased hypermutation of viral RNA genomes could be due to unwinding/modification of double-stranded RNA. Cell 56: 331. [PubMed: 2914324]
    175.
    Keegan L.P., Leroy A., Sproul D. and O‘Connell M.A. (2004) Adenosine deaminases acting on RNA (ADARs): RNA-editing enzymes. Genome Biology 5: 209. [PMC free article: PMC395743] [PubMed: 14759252]
    176.
    Valente L. and Nishikura K. (2005) ADAR gene family and A-to-I RNA editing: Diverse roles in posttranscriptional gene regulation. Progress in Nucleic Acid Research and Molecular Biology 79: 299–338. [PubMed: 16096031]
    177.
    Nishikura K. (2010) Functions and regulation of RNA editing by ADAR deaminases. Annual Review of Biochemistry 79: 321–349. [PMC free article: PMC2953425] [PubMed: 20192758]
    178.
    Farajollahi S. and Maas S. (2010) Molecular diversity through RNA editing: A balancing act. Trends in Genetics 26: 221–230. [PMC free article: PMC2865426] [PubMed: 20395010]
    179.
    Savva Y.A., Rieder L.E. and Reenan R.A. (2012) The ADAR protein family. Genome Biology 13: 252. [PMC free article: PMC3580408] [PubMed: 23273215]
    180.
    Walkley C.R. and Li J.B. (2017) Rewriting the transcriptome: Adenosine-to-inosine RNA editing by ADARs. Genome Biology 18: 205. [PMC free article: PMC5663115] [PubMed: 29084589]
    181.
    Tan M.H. et al. (2017) Dynamic landscape and regulation of RNA editing in mammals. Nature 550: 249–254. [PMC free article: PMC5723435] [PubMed: 29022589]
    182.
    Laurencikiene J., Kallman A.M., Fong N., Bentley D.L. and Ohman M. (2006) RNA editing and alternative splicing: The importance of co-transcriptional coordination. EMBO Reports 7: 303–307. [PMC free article: PMC1456888] [PubMed: 16440002]
    183.
    Rodriguez J., Menet J.S. and Rosbash M. (2012) Nascent-seq indicates widespread cotranscriptional RNA editing in Drosophila. Molecular Cell 47: 27–37. [PMC free article: PMC3409466] [PubMed: 22658416]
    184.
    Wong S.K., Sato S. and Lazinski D.W. (2001) Substrate recognition by ADAR1 and ADAR2. RNA 7: 846–858. [PMC free article: PMC1370134] [PubMed: 11421361]
    185.
    Uzonyi A. et al. (2021) Deciphering the principles of the RNA editing code via large-scale systematic probing. Molecular Cell 81: 2374–2387. [PubMed: 33905683]
    186.
    Stefl R. and Allain F.H. (2005) A novel RNA pentaloop fold involved in targeting ADAR2. RNA 11: 592–597. [PMC free article: PMC1370747] [PubMed: 15840813]
    187.
    Bass B.L. (2002) RNA editing by adenosine deaminases that act on RNA. Annual Review of Biochemistry 71: 817–846. [PMC free article: PMC1823043] [PubMed: 12045112]
    188.
    Sapiro A.L. et al. (2019) Illuminating spatial A-to-I RNA editing signatures within the Drosophila brain. Proceedings of the National Academy of Sciences USA 116: 2318–2327. [PMC free article: PMC6369821] [PubMed: 30659150]
    189.
    Anantharaman A. et al. (2017) ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins. Nucleic Acids Research 45: 4189–4201. [PMC free article: PMC5397167] [PubMed: 28053121]
    190.
    Gong C. and Maquat L.E. (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470: 284–288. [PMC free article: PMC3073508] [PubMed: 21307942]
    191.
    Wagner R.W., Smith J.E., Cooperman B.S. and Nishikura K. (1989) A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proceedings of the National Academy of Sciences USA 86: 2647–2651. [PMC free article: PMC286974] [PubMed: 2704740]
    192.
    Sommer B., Köhler M., Sprengel R. and Seeburg P.H. (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67: 11–19. [PubMed: 1717158]
    193.
    Melcher T. et al. (1996) A mammalian RNA editing enzyme. Nature 379: 460–464. [PubMed: 8559253]
    194.
    Seeburg P.H. (2002) A-to-I editing: New and old sites, functions and speculations. Neuron 35: 17–20. [PubMed: 12123604]
    195.
    Hoopengardner B., Bhalla T., Staber C. and Reenan R. (2003) Nervous system targets of RNA editing identified by comparative genomics. Science 301: 832–836. [PubMed: 12907802]
    196.
    Schmauss C. (2003) Serotonin 2C receptors: Suicide, serotonin, and runaway RNA editing. Neuroscientist 9: 237–242. [PubMed: 12934707]
    197.
    Barlati S. and Barbon A. (2005) RNA editing: A molecular mechanism for the fine modulation of neuronal transmission. Acta Neurochirurgica Supplementum 93: 53–57. [PubMed: 15986727]
    198.
    Behm M., Wahlstedt H., Widmark A., Eriksson M. and Öhman M. (2017) Accumulation of nuclear ADAR2 regulates adenosine-to-inosine RNA editing during neuronal development. Journal of Cell Science 130: 745–753. [PubMed: 28082424]
    199.
    Yablonovitch A.L., Deng P., Jacobson D. and Li J.B. (2017) The evolution and adaptation of A-to-I RNA editing. PLOS Genetics 13: e1007064. [PMC free article: PMC5705066] [PubMed: 29182635]
    200.
    Mattick J.S. and Mehler M.F. (2008) RNA editing, DNA recoding and the evolution of human cognition. Trends in Neuroscience 31: 227–233. [PubMed: 18395806]
    201.
    Palladino M.J., Keegan L.P., O‘Connell M.A. and Reenan R.A. (2000) dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing. RNA 6: 1004–1018. [PMC free article: PMC1369976] [PubMed: 10917596]
    202.
    Slavov D. and Gardiner K. (2002) Phylogenetic comparison of the pre-mRNA adenosine deaminase ADAR2 genes and transcripts: Conservation and diversity in editing site sequence and alternative splicing patterns. Gene 299: 83–94. [PubMed: 12459255]
    203.
    Dawson T.R., Sansam C.L. and Emeson R.B. (2004) Structure and sequence determinants required for the RNA editing of ADAR2 substrates. Journal of Biological Chemistry 279: 4941–4951. [PubMed: 14660658]
    204.
    Xiang J.-F. et al. (2018) N6-methyladenosines modulate A-to-I RNA editing. Molecular Cell 69: 126–135. [PubMed: 29304330]
    205.
    Rueter S.M., Dawson T.R. and Emeson R.B. (1999) Regulation of alternative splicing by RNA editing. Nature 399: 75–80. [PubMed: 10331393]
    206.
    Zhang Z. and Carmichael G.G. (2001) The fate of dsRNA in the nucleus: A p54nrb-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell 106: 465–476. [PubMed: 11525732]
    207.
    DeCerbo J. and Carmichael G.G. (2005) Retention and repression: Fates of hyperedited RNAs in the nucleus. Current Opinion in Cell Biology 17: 302–308. [PubMed: 15901501]
    208.
    Blow M.J. et al. (2006) RNA editing of human microRNAs. Genome Biology 7: R27. [PMC free article: PMC1557993] [PubMed: 16594986]
    209.
    Yang W. et al. (2006) Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nature Structural & Molecular Biology 13: 13–21. [PMC free article: PMC2950615] [PubMed: 16369484]
    210.
    Kawahara Y., Zinshteyn B., Chendrimada T.P., Shiekhattar R. and Nishikura K. (2007) RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Reports 8: 763–769. [PMC free article: PMC1978079] [PubMed: 17599088]
    211.
    Kawahara Y. et al. (2007) Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 315: 1137–1140. [PMC free article: PMC2953418] [PubMed: 17322061]
    212.
    Macbeth M.R. et al. (2005) Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science 309: 1534–1539. [PMC free article: PMC1850959] [PubMed: 16141067]
    213.
    Valastro B. et al. (2001) Inositol hexakisphosphate-mediated regulation of glutamate receptors in rat brain sections. Hippocampus 11: 673–682. [PubMed: 11811661]
    214.
    Chalk A.M., Taylor S., Heraud-Farlow J.E. and Walkley C.R. (2019) The majority of A-to-I RNA editing is not required for mammalian homeostasis. Genome Biology 20: 268. [PMC free article: PMC6900863] [PubMed: 31815657]
    215.
    Tan B.Z., Huang H., Lam R. and Soong T.W. (2009) Dynamic regulation of RNA editing of ion channels and receptors in the mammalian nervous system. Molecular Brain 2: 13. [PMC free article: PMC2694175] [PubMed: 19480689]
    216.
    Herbert A., Lowenhaupt K., Spitzner J. and Rich A. (1995) Chicken double-stranded RNA adenosine deaminase has apparent specificity for Z-DNA. Proceedings of the National Academy of Sciences USA 92: 7550–7554. [PMC free article: PMC41377] [PubMed: 7638229]
    217.
    Herbert A. et al. (1997) A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase. Proceedings of the National Academy of Sciences USA 94: 8421–8426. [PMC free article: PMC22942] [PubMed: 9237992]
    218.
    Herbert A. et al. (1998) The Zalpha domain from human ADAR1 binds to the Z-DNA conformer of many different sequences. Nucleic Acids Research 26: 3486–3493. [PMC free article: PMC147729] [PubMed: 9671809]
    219.
    Herbert A. and Rich A. (1999) Left-handed Z-DNA: Structure and function. Genetica 106: 37–47. [PubMed: 10710708]
    220.
    Herbert A. and Rich A. (2001) The role of binding domains for dsRNA and Z-DNA in the in vivo editing of minimal substrates by ADAR1. Proceedings of the National Academy of Sciences USA 98: 12132–12137. [PMC free article: PMC59780] [PubMed: 11593027]
    221.
    Mirkin S.M. (2008) Discovery of alternative DNA structures: A heroic decade (1979–1989). Frontiers in Bioscience 13: 1064–1071. [PubMed: 17981612]
    222.
    Herbert A. (1996) RNA editing, introns and evolution. Trends in Genetics 12: 6–9. [PubMed: 8741851]
    223.
    Herbert A. (2019) Z-DNA and Z-RNA in human disease. Communications Biology 2: 7. [PMC free article: PMC6323056] [PubMed: 30729177]
    224.
    Kim J.I. et al. (2021) RNA editing at a limited number of sites is sufficient to prevent MDA5 activation in the mouse brain. PLOS Genetics 17: e1009516. [PMC free article: PMC8118328] [PubMed: 33983932]
    225.
    Liddicoat B.J. et al. (2015) RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science 349: 1115–1120. [PMC free article: PMC5444807] [PubMed: 26275108]
    226.
    Ahmad S. et al. (2018) Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation. Cell 172: 797–810. [PMC free article: PMC5807104] [PubMed: 29395326]
    227.
    Chung H. et al. (2018) Human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell 172: 811–824. [PMC free article: PMC5831367] [PubMed: 29395325]
    228.
    Terajima H. et al. (2021) N6-methyladenosine promotes induction of ADAR1-mediated A-to-I RNA editing to suppress aberrant antiviral innate immune responses. PLOS Biology 19: e3001292. [PMC free article: PMC8320976] [PubMed: 34324489]
    229.
    Marshall P.R. et al. (2020) Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction. Nature Neuroscience 23: 718–729. [PMC free article: PMC7269834] [PubMed: 32367065]
    230.
    McFadden M.J. and Horner S.M. (2021) N6-methyladenosine regulates host responses to viral infection. Trends in Biochemical Sciences 46: 366–377. [PMC free article: PMC8052259] [PubMed: 33309325]
    231.
    Hartner J.C. et al. (2004) Liver disintegration in the mouse embryocaused by deficiency in the RNA-editing enzyme ADAR1. Journal of Biological Chemistry 279: 4894–4902. [PubMed: 14615479]
    232.
    Hartner J.C., Walkley C.R., Lu J. and Orkin S.H. (2009) ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nature Immunology 10: 109–115. [PMC free article: PMC2701568] [PubMed: 19060901]
    233.
    Rice G.I. et al. (2012) Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nature Genetics 44: 1243–1248. [PMC free article: PMC4154508] [PubMed: 23001123]
    234.
    Crow Y.J. and Manel N. (2015) Aicardi–Goutières syndrome and the type I interferonopathies. Nature Reviews Immunology 15: 429–440. [PubMed: 26052098]
    235.
    Heraud-Farlow J.E. et al. (2017) Protein recoding by ADAR1-mediated RNA editing is not essential for normal development and homeostasis. Genome Biology 18: 166. [PMC free article: PMC5585977] [PubMed: 28874170]
    236.
    Tariq A. and Jantsch M. (2012) Transcript diversification in the nervous system: A to I RNA-editing in CNS function and disease development. Frontiers in Neuroscience 6: 99. [PMC free article: PMC3391646] [PubMed: 22787438]
    237.
    Sansam C.L., Wells K.S. and Emeson R.B. (2003) Modulation of RNA editing by functional nucleolar sequestration of ADAR2. Proceedings of the National Academy of Sciences USA 100: 14018–14023. [PMC free article: PMC283538] [PubMed: 14612560]
    238.
    Vitali P. et al. (2005) ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs. Journal of Cell Biology 169: 745–753. [PMC free article: PMC2171610] [PubMed: 15939761]
    239.
    Tan T.Y. et al. (2020) Bi-allelic ADARB1 variants associated with microcephaly, intellectual disability, and seizures. American Journal of Human Genetics 106: 467–483. [PMC free article: PMC7118584] [PubMed: 32220291]
    240.
    Maroofian R. et al. (2021) Biallelic variants in ADARB1, encoding a dsRNA-specific adenosine deaminase, cause a severe developmental and epileptic encephalopathy. Journal of Medical Genetics 58: 495–504. [PMC free article: PMC8327408] [PubMed: 32719099]
    241.
    Higuchi M. et al. (2000) Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 406: 78–81. [PubMed: 10894545]
    242.
    Aruscavage P.J. and Bass B.L. (2000) A phylogenetic analysis reveals an unusual sequence conservation within introns involved in RNA editing. RNA 6: 257–269. [PMC free article: PMC1369911] [PubMed: 10688364]
    243.
    Maas S., Patt S., Schrey M. and Rich A. (2001) Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proceedings of the National Academy of Sciences USA 98: 14687–14692. [PMC free article: PMC64742] [PubMed: 11717408]
    244.
    Seifert G., Zhou M. and Steinhäuser C. (1997) Analysis of AMPA receptor properties during postnatal development of mouse hippocampal astrocytes. Journal of Neurophysiology 78: 2916–2923. [PubMed: 9405512]
    245.
    Jakowec M.W., Jackson-Lewis V., Chen X., Langston J.W. and Przedborski S. (1998) The postnatal development of AMPA receptor subunits in the basal ganglia of the rat. Developmental Neuroscience 20: 19–33. [PubMed: 9600387]
    246.
    Petralia R.S. et al. (1999) Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nature Neuroscience 2: 31–36. [PubMed: 10195177]
    247.
    Gordon S., Akopyan G., Garban H. and Bonavida B. (2006) Transcription factor YY1: Structure, function, and therapeutic implications in cancer biology. Oncogene 25: 1125–1142. [PubMed: 16314846]
    248.
    Yoon Y.J., White S.L., Ni X., Gokin A.P. and Martin-Caraballo M. (2012) Downregulation of GluA2 AMPA receptor subunits reduces the dendritic arborization of developing spinal motoneurons. PLOS ONE 7: e49879. [PMC free article: PMC3511505] [PubMed: 23226228]
    249.
    Tzakis N. and Holahan M.R. (2020) Investigation of GluA1 and GluA2 AMPA receptor subtype distribution in the hippocampus and anterior cingulate cortex of Long Evans rats during development. IBRO Reports 8: 91–100. [PMC free article: PMC7152689] [PubMed: 32300670]
    250.
    Khan A. et al. (2020) Membrane and synaptic defects leading to neurodegeneration in Adar mutant Drosophila are rescued by increased autophagy. BMC Biology 18: 15. [PMC free article: PMC7020516] [PubMed: 32059717]
    251.
    Vallecillo-Viejo I.C. et al. (2020) Spatially regulated editing of genetic information within a neuron. Nucleic Acids Research 48: 3999–4012. [PMC free article: PMC7192619] [PubMed: 32201888]
    252.
    Horsch M. et al. (2011) Requirement of the RNA-editing enzyme ADAR2 for normal physiology in mice. Journal of Biological Chemistry 286: 18614–18622. [PMC free article: PMC3099677] [PubMed: 21467037]
    253.
    Maas S. and Gommans W.M. (2009) Novel exon of mammalian ADAR2 extends open reading frame. PLOS ONE 4: e4225. [PMC free article: PMC2626628] [PubMed: 19156214]
    254.
    Gerber A., O‘Connell M.A. and Keller W. (1997) Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette. RNA 3: 453–463. [PMC free article: PMC1369496] [PubMed: 9149227]
    255.
    Keegan L.P. et al. (2005) Tuning of RNA editing by ADAR is required in Drosophila. EMBO Journal 24: 2183–2193. [PMC free article: PMC1150885] [PubMed: 15920480]
    256.
    Deng P. et al. (2020) Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila. Nature Communications 11: 1580. [PMC free article: PMC7101428] [PubMed: 32221286]
    257.
    Palladino M.J., Keegan L.P., O‘Connell M.A. and Reenan R.A. (2000) A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell 102: 437–449. [PubMed: 10966106]
    258.
    Porath H.T. et al. (2019) RNA editing is abundant and correlates with task performance in a social bumblebee. Nature Communications 10: 1605. [PMC free article: PMC6453909] [PubMed: 30962428]
    259.
    Tonkin L.A. et al. (2002) RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans. EMBO Journal 21: 6025–6035. [PMC free article: PMC137199] [PubMed: 12426375]
    260.
    Sebastiani P. et al. (2009) RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. PLOS ONE 4: e8210. [PMC free article: PMC2788130] [PubMed: 20011587]
    261.
    Goldstein B. et al. (2017) A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression. Genome Research 27: 462–470. [PMC free article: PMC5340973] [PubMed: 28031250]
    262.
    Melcher T. et al. (1996) RED2, a brain-specific member of the RNA-specific adenosine deaminase family. Journal of Biological Chemistry 271: 31795–31798. [PubMed: 8943218]
    263.
    Chen C.-X. et al. (2000) A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. RNA 6: 755–767. [PMC free article: PMC1369955] [PubMed: 10836796]
    264.
    Cho D.-S.C. et al. (2003) Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. Journal of Biological Chemistry 278: 17093–17102. [PubMed: 12618436]
    265.
    Mladenova D. et al. (2018) Adar3 Is Involved in learning and memory in mice. Frontiers in Neuroscience 12: 243. [PMC free article: PMC5914295] [PubMed: 29719497]
    266.
    Patton D.E., Silva T. and Bezanilla F. (1997) RNA editing generates a diverse array of transcripts encoding squid Kv2 K+ channels with altered functional properties. Neuron 19: 711–722. [PubMed: 9331360]
    267.
    Alon S. et al. (2015) The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing. eLife 4: e05198. [PMC free article: PMC4384741] [PubMed: 25569156]
    268.
    Albertin C.B. et al. (2015) The octopus genome and the evolution of cephalopod neural and morphological novelties. Nature 524: 220–224. [PMC free article: PMC4795812] [PubMed: 26268193]
    269.
    Liscovitch-Brauer N. et al. (2017) Trade-off between transcriptome plasticity and genome evolution in cephalopods. Cell 169: 191–202. [PMC free article: PMC5499236] [PubMed: 28388405]
    270.
    Levanon E.Y. et al. (2004) Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nature Biotechnology 22: 1001–1005. [PubMed: 15258596]
    271.
    Athanasiadis A., Rich A. and Maas S. (2004) Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLOS Biology 2: e391. [PMC free article: PMC526178] [PubMed: 15534692]
    272.
    Kim D.D. et al. (2004) Widespread RNA editing of embedded alu elements in the human transcriptome. Genome Research 14: 1719–1725. [PMC free article: PMC515317] [PubMed: 15342557]
    273.
    Blow M., Futreal P.A., Wooster R. and Stratton M.R. (2004) A survey of RNA editing in human brain. Genome Research 14: 2379–2387. [PMC free article: PMC534661] [PubMed: 15545495]
    274.
    Porath H.T., Carmi S. and Levanon E.Y. (2014) A genome-wide map of hyper-edited RNA reveals numerous new sites. Nature Communications 5: 4726. [PMC free article: PMC4365171] [PubMed: 25158696]
    275.
    Solomon O. et al. (2017) RNA editing by ADAR1 leads to context-dependent transcriptome-wide changes in RNA secondary structure. Nature Communications 8: 1440. [PMC free article: PMC5682290] [PubMed: 29129909]
    276.
    Paz-Yaacov N. et al. (2010) Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates. Proceedings of the National Academy of Sciences USA 107: 12174–12179. [PMC free article: PMC2901480] [PubMed: 20566853]
    277.
    Britten R.J., Baron W.F., Stout D.B. and Davidson E.H. (1988) Sources and evolution of human Alu repeated sequences. Proceedings of the National Academy of Sciences USA 85: 4770–4774. [PMC free article: PMC280517] [PubMed: 3387437]
    278.
    Liu G.E., Alkan C., Jiang L., Zhao S. and Eichler E.E. (2009) Comparative analysis of Alu repeats in primate genomes. Genome Research 19: 876–885. [PMC free article: PMC2675976] [PubMed: 19411604]
    279.
    Bazak L. et al. (2014) A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes. Genome Research 24: 365–376. [PMC free article: PMC3941102] [PubMed: 24347612]
    280.
    Liu W.M., Chu W.M., Choudary P.V. and Schmid C.W. (1995) Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts. Nucleic Acids Research 23: 1758–1765. [PMC free article: PMC306933] [PubMed: 7784180]
    281.
    Lev-Maor G., Sorek R., Shomron N. and Ast G. (2003) The birth of an alternatively spliced exon: 3′ splice-site selection in Alu exons. Science 300: 1288–1291. [PubMed: 12764196]
    282.
    Jurka J. (2004) Evolutionary impact of human Alu repetitive elements. Current Opinion in Genetics and Development 14: 603–608. [PubMed: 15531153]
    283.
    Krull M., Brosius J. and Schmitz J. (2005) Alu-SINE exonization: En route to protein-coding function. Molecular Biology and Evolution 22: 1702–1711. [PubMed: 15901843]
    284.
    Hasler J. and Strub K. (2006) Alu elements as regulators of gene expression. Nucleic Acids Research 34: 5491–5497. [PMC free article: PMC1636486] [PubMed: 17020921]
    285.
    Britten R.J. (2010) Transposable element insertions have strongly affected human evolution. Proceedings of the National Academy of Sciences USA 107: 19945–19948. [PMC free article: PMC2993358] [PubMed: 21041622]
    286.
    Jády B.E., Ketele A. and Kiss T. (2012) Human intron-encoded Alu RNAs are processed and packaged into Wdr79-associated nucleoplasmic box H/ACA RNPs. Genes & Development 26: 1897–1910. [PMC free article: PMC3435494] [PubMed: 22892240]
    287.
    Lubelsky Y. and Ulitsky I. (2018) Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells. Nature 555: 107–111. [PMC free article: PMC6047738] [PubMed: 29466324]
    288.
    Cheng Y. et al. (2020) Increased processing of SINE B2 ncRNAs unveils a novel type of transcriptome deregulation in amyloid beta neuropathology. eLife 9: e61265. [PMC free article: PMC7717908] [PubMed: 33191914]
    289.
    Hernandez A.J. et al. (2020) B2 and ALU retrotransposons are self-cleaving ribozymes whose activity is enhanced by EZH2. Proceedings of the National Academy of Sciences USA 117: 415–425. [PMC free article: PMC6955291] [PubMed: 31871160]
    290.
    Cheng Y. et al. (2021) Increased Alu RNA processing in Alzheimer brains is linked to gene expression changes. EMBO Reports 22: e52255. [PMC free article: PMC8097388] [PubMed: 33645898]
    291.
    Li W.Y., Reddy R., Henning D., Epstein P. and Busch H. (1982) Nucleotide sequence of 7S RNA. Homology to Alu DNA and La 4.5S RNA. Journal of Biological Chemistry 257: 5136–5142. [PubMed: 6802847]
    292.
    Labuda D. and Zietkiewicz E. (1994) Evolution of secondary structure in the family of 7SL-like RNAs. Journal of Molecular Evolution 39: 506–518. [PubMed: 7528809]
    293.
    Navaratnam N. and Sarwar R. (2006) An overview of cytidine deaminases. International Journal of Hematology 83: 195–200. [PubMed: 16720547]
    294.
    Conticello S.G. (2008) The AID/APOBEC family of nucleic acid mutators. Genome Biology 9: 229. [PMC free article: PMC2481415] [PubMed: 18598372]
    295.
    Münk C., Willemsen A. and Bravo I.G. (2012) An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals. BMC Evolutionary Biology 12: 71. [PMC free article: PMC3495650] [PubMed: 22640020]
    296.
    Salter J.D., Bennett R.P. and Smith H.C. (2016) The APOBEC protein family: United by structure, divergent in function. Trends in Biochemical Sciences 41: 578–594. [PMC free article: PMC4930407] [PubMed: 27283515]
    297.
    Chen S. et al. (1987) Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon. Science 238: 363–366. [PubMed: 3659919]
    298.
    Powell L.M. et al. (1987) A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell 50: 831–840. [PubMed: 3621347]
    299.
    Davidson N.O. and Shelness G.S. (2000) Apolipoprotein B: mRNA editing, lipoprotein assembly, and presecretory degradation. Annual Review of Nutrition 20: 169–193. [PubMed: 10940331]
    300.
    Liu M.-C. et al. (2018) AID/APOBEC-like cytidine deaminases are ancient innate immune mediators in invertebrates. Nature Communications 9: 1948. [PMC free article: PMC5956068] [PubMed: 29769532]
    301.
    Schutsky E.K., Nabel C.S., Davis A.K.F., DeNizio J.E. and Kohli R.M. (2017) APOBEC3A efficiently deaminates methylated, but not TET-oxidized, cytosine bases in DNA. Nucleic Acids Research 45: 7655–7665. [PMC free article: PMC5570014] [PubMed: 28472485]
    302.
    Chahwan R., Wontakal S.N. and Roa S. (2010) Crosstalk between genetic and epigenetic information through cytosine deamination. Trends in Genetics 26: 443–448. [PubMed: 20800313]
    303.
    Nelson V.R., Heaney J.D., Tesar P.J., Davidson N.O. and Nadeau J.H. (2012) Transgenerational epigenetic effects of the Apobec1 cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability. Proceedings of the National Academy of Sciences USA 109: E2766–73. [PMC free article: PMC3478648] [PubMed: 22923694]
    304.
    Severi F., Chicca A. and Conticello S.G. (2010) Analysis of reptilian APOBEC1 suggests that RNA editing may not be its ancestral function. Molecular Biology and Evolution 28: 1125–1129. [PubMed: 21172829]
    305.
    Rogozin I.B., Basu M.K., Jordan I.K., Pavlov Y.I. and Koonin E.V. (2005) APOBEC4, a new member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases predicted by computational analysis. Cell Cycle 4: 1281–1285. [PubMed: 16082223]
    306.
    Ito J., Gifford R.J. and Sato K. (2020) Retroviruses drive the rapid evolution of mammalian APOBEC3 genes. Proceedings of the National Academy of Sciences USA 117: 610–618. [PMC free article: PMC6955324] [PubMed: 31843890]
    307.
    Sawyer S.L., Emerman M. and Malik H.S. (2004) Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G. PLOS Biology 2: e275. [PMC free article: PMC479043] [PubMed: 15269786]
    308.
    Zhang J. and Webb D.M. (2004) Rapid evolution of primate antiviral enzyme APOBEC3G. Human Molecular Genetics 13: 1785–1791. [PubMed: 15198990]
    309.
    LaRue R.S. et al. (2009) Guidelines for naming nonprimate APOBEC3 genes and proteins. Journal of Virology 83: 494–497. [PMC free article: PMC2612408] [PubMed: 18987154]
    310.
    Krishnan A., Iyer L.M., Holland S.J., Boehm T. and Aravind L. (2018) Diversification of AID/APOBEC-like deaminases in metazoa: Multiplicity of clades and widespread roles in immunity. Proceedings of the National Academy of Sciences USA 115: E3201–10. [PMC free article: PMC5889660] [PubMed: 29555751]
    311.
    Koning F.A. et al. (2009) Defining APOBEC3 expression patterns in human tissues and hematopoietic cell subsets. Journal of Virology 83: 9474–9485. [PMC free article: PMC2738220] [PubMed: 19587057]
    312.
    Hill M.S. et al. (2006) APOBEC3G expression is restricted to neurons in the brains of pigtailed macaques. AIDS Research and Human Retroviruses 22: 541–550. [PubMed: 16796529]
    313.
    Harris R.S. and Dudley J.P. (2015) APOBECs and virus restriction. Virology 479: 131–145. [PMC free article: PMC4424171] [PubMed: 25818029]
    314.
    Chiu Y.-L. and Greene W.C. (2008) The APOBEC3 cytidine deaminases: An innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annual Review of Immunology 26: 317–353. [PubMed: 18304004]
    315.
    Koyama T. et al. (2013) APOBEC3G oligomerization is associated with the inhibition of both Alu and Line-1 retrotransposition. PLOS ONE 8: e84228. [PMC free article: PMC3868573] [PubMed: 24367644]
    316.
    Mustafin R.N. and Khusnutdinova E.K. (2020) Involvement of transposable elements in neurogenesis. Vavilov Journal of Genetics and Breeding 24: 209–218. [PMC free article: PMC7893149] [PubMed: 33659801]
    317.
    Muotri A.R. et al. (2005) Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition. Nature 435: 903–910. [PubMed: 15959507]
    318.
    Coufal N.G. et al. (2009) L1 retrotransposition in human neural progenitor cells. Nature 460: 1127–1131. [PMC free article: PMC2909034] [PubMed: 19657334]
    319.
    Muotri A.R. et al. (2010) L1 retrotransposition in neurons is modulated by MeCP2. Nature 468: 443–446. [PMC free article: PMC3059197] [PubMed: 21085180]
    320.
    Salvador-Palomeque C. et al. (2019) Dynamic methylation of an L1 transduction family during reprogramming and neurodifferentiation. Molecular and Cellular Biology 39: e00499. [PMC free article: PMC6425141] [PubMed: 30692270]
    321.
    Sanchez-Luque F.J. et al. (2019) LINE-1 evasion of epigenetic repression in humans. Molecular Cell 75: 590–604. [PubMed: 31230816]
    322.
    Baillie J.K. et al. (2011) Somatic retrotransposition alters the genetic landscape of the human brain. Nature 479: 534–537. [PMC free article: PMC3224101] [PubMed: 22037309]
    323.
    Rowe H.M. et al. (2010) KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463: 237–240. [PubMed: 20075919]
    324.
    Thomas C.A. et al. (2017) Modeling of TREX1-dependent autoimmune disease using human stem cells highlights L1 accumulation as a source of neuroinflammation. Cell Stem Cell 21: 319–331. [PMC free article: PMC5591075] [PubMed: 28803918]
    325.
    Jönsson M.E., Garza R., Johansson P.A. and Jakobsson J. (2020) Transposable elements: A common feature of neurodevelopmental and neurodegenerative disorders. Trends in Genetics 36: 610–623. [PubMed: 32499105]
    326.
    Turelli P. et al. (2020) Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons. Science Advances 6: eaba3200. [PMC free article: PMC7455193] [PubMed: 32923624]
    327.
    Jönsson M.E. et al. (2021) Activation of endogenous retroviruses during brain development causes an inflammatory response. EMBO Journal 40: e106423. [PMC free article: PMC8090857] [PubMed: 33644903]
    328.
    Marchetto M.C.N. et al. (2013) Differential L1 regulation in pluripotent stem cells of humans and apes. Nature 503: 525–529. [PMC free article: PMC4064720] [PubMed: 24153179]
    329.
    Jönsson M.E. et al. (2019) Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors. Nature Communications 10: 3182. [PMC free article: PMC6639357] [PubMed: 31320637]
    330.
    Swanson L., Newman E., Araque A. and Dubinsky J.M.A., Katie (2017) The Beautiful Brain: The Drawings of Santiago Ramón y Cajal (Abrams, New York).
    331.
    Tan L. et al. (2021) Changes in genome architecture and transcriptional dynamics progress independently of sensory experience during post-natal brain development. Cell 184: 741–758. [PubMed: 33484631]
    332.
    Edelman G.M. (1978) The Mindful Brain: Cortical Organization and the Group-Selective Theory of Higher Brain Function (MIT Press, New York).
    333.
    Edelman G.M. (1988) Topobiology: An Introduction to Molecular Embryology (Basic Books, New York). [PubMed: 17808269]
    334.
    Mateos-Aparicio P. and Rodríguez-Moreno A. (2019) The impact of studying brain plasticity. Frontiers in Cellular Neuroscience 13: 66. [PMC free article: PMC6400842] [PubMed: 30873009]
    335.
    Niemi M.E.K. et al. (2018) Common genetic variants contribute to risk of rare severe neurodevelopmental disorders. Nature 562: 268–271. [PMC free article: PMC6726472] [PubMed: 30258228]
    336.
    Asgari Y., Heng J.I.T., Lovell N., Forrest A.R.R. and Alinejad-Rokny H. (2020) Evidence for enhancer noncoding RNAs (enhancer-ncRNAs) with gene regulatory functions relevant to neurodevelopmental disorders. bioRxiv: 2020.05.16.087395v2.
    337.
    Sicot G. and Gomes-Pereira M. (2013) RNA toxicity in human disease and animal models: From the uncovering of a new mechanism to the development of promising therapies. Biochimica et Biophysica Acta 1832: 1390–1409. [PubMed: 23500957]
    338.
    Riva P., Ratti A. and Venturin M. (2016) The long non-coding RNAs in neurodegenerative diseases: Novel mechanisms of pathogenesis. Current Alzheimer Research 13: 1219–1231. [PubMed: 27338628]
    339.
    Wan P., Su W. and Zhuo Y. (2017) The role of long noncoding RNAs in neurodegenerative diseases. Molecular Neurobiology 54: 2012–2021. [PubMed: 26910817]
    340.
    Prabhakar S., Noonan J.P., Paabo S. and Rubin E.M. (2006) Accelerated evolution of conserved noncoding sequences in humans. Science 314: 786. [PubMed: 17082449]
    341.
    Xu A.G. et al. (2010) Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq. PLOS Computational Biology 6: e1000843. [PMC free article: PMC2895644] [PubMed: 20617162]
    342.
    Liu S.J. et al. (2016) Single-cell analysis of long non-coding RNAs in the developing human neocortex. Genome Biology 17: 67. [PMC free article: PMC4831157] [PubMed: 27081004]
    343.
    Ma Q. and Chang H.Y. (2016) Single-cell profiling of lncRNAs in the developing human brain. Genome Biology 17: 68. [PMC free article: PMC4831122] [PubMed: 27079200]
    344.
    Eze U.C., Bhaduri A., Haeussler M., Nowakowski T.J. and Kriegstein A.R. (2021) Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia. Nature Neuroscience 24: 584–594. [PMC free article: PMC8012207] [PubMed: 33723434]
    345.
    Bocchi V.D. et al. (2021) The coding and long noncoding single-cell atlas of the developing human fetal striatum. Science 372: eabf5759. [PubMed: 33958447]
    346.
    Briggs J.A., Wolvetang E.J., Mattick J.S., Rinn J.L. and Barry G. (2015) Mechanisms of long non-coding RNAs in mammalian nervous system development, plasticity, disease, and evolution. Neuron 88: 861–877. [PubMed: 26637795]
    347.
    Zwir I. et al. (2022) Evolution of genetic networks for human creativity. Molecular Psychiatry 27: 354–376. [PMC free article: PMC8960414] [PubMed: 33879864]
    348.
    Sas-Nowosielska H. and Magalska A. (2021) Long noncoding RNAs—crucial players organizing the landscape of the neuronal nucleus. International Journal of Molecular Sciences 22: 3478. [PMC free article: PMC8037058] [PubMed: 33801737]
    349.
    Trizzino M. et al. (2017) Transposable elements are the primary source of novelty in primate gene regulation. Genome Research 27: 1623–1633. [PMC free article: PMC5630026] [PubMed: 28855262]
    350.
    Cosby R.L. et al. (2021) Recurrent evolution of vertebrate transcription factors by transposase capture. Science 371: eabc6405. [PMC free article: PMC8186458] [PubMed: 33602827]
    351.
    Mercer T.R. et al. (2011) Expression of distinct RNAs from 3′ untranslated regions. Nucleic Acids Research 39: 2393–2403. [PMC free article: PMC3064787] [PubMed: 21075793]
    352.
    Kocabas A., Duarte T., Kumar S. and Hynes M.A. (2015) Widespread differential expression of coding region and 3′UTR sequences in neurons and other tissues. Neuron 88: 1149–1156. [PubMed: 26687222]
    353.
    Andreassi C. et al. (2021) Cytoplasmic cleavage of IMPA1 3′ UTR is necessary for maintaining axon integrity. Cell Reports 34: 108778. [PMC free article: PMC7918530] [PubMed: 33626357]
    354.
    Smalheiser N.R. (2014) The RNA-centred view of the synapse: Non-coding RNAs and synaptic plasticity. Philosophical Transactions of the Royal Society B: Biological Sciences 369: 20130504. [PMC free article: PMC4142025] [PubMed: 25135965]
    355.
    Rogelj B. and Giese K.P. (2004) Expression and function of brain specific small RNAs. Reviews in Neuroscience 15: 185–198. [PubMed: 15357141]
    356.
    Rajasethupathy P. et al. (2012) A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 149: 693–707. [PMC free article: PMC3442366] [PubMed: 22541438]
    357.
    Zuo L., Wang Z., Tan Y., Chen X. and Luo X. (2016) piRNAs and their functions in the brain. International Journal of Human Genetics 16: 53–60. [PMC free article: PMC4976825] [PubMed: 27512315]
    358.
    Gasperini C. et al. (2020) The piRNA pathway sustains adult neurogenesis by repressing protein synthesis. bioRxiv: 2020.09.15.297739.
    359.
    Ashraf S.I. and Kunes S. (2006) A trace of silence: Memory and microRNA at the synapse. Current Opinion in Neurobiology 16: 535–539. [PubMed: 16962314]
    360.
    Sambandan S. et al. (2017) Activity-dependent spatially localized miRNA maturation in neuronal dendrites. Science 355: 634–637. [PubMed: 28183980]
    361.
    Zimmer-Bensch G. (2019) Emerging roles of long non-coding RNAs as drivers of brain evolution. Cells 8: 1399. [PMC free article: PMC6912723] [PubMed: 31698782]
    362.
    Ng S.-Y., Lin L., Soh B.S. and Stanton L.W. (2013) Long noncoding RNAs in development and disease of the central nervous system. Trends in Genetics 29: 461–468. [PubMed: 23562612]
    363.
    Clark B.S. and Blackshaw S. (2017) Understanding the role of lncRNAs in nervous system development. Advances in Experimental Medicine and Biology 1008: 253–282. [PMC free article: PMC5890441] [PubMed: 28815543]
    364.
    Korneev S.A. et al. (2013) Axonal trafficking of an antisense RNA transcribed from a pseudogene is regulated by classical conditioning. Scientific Reports 3: 1027. [PMC free article: PMC3537157] [PubMed: 23293742]
    365.
    Kleaveland B., Shi C.Y., Stefano J. and Bartel D.P. (2018) A network of noncoding regulatory RNAs acts in the mammalian brain. Cell 174: 350–362. [PMC free article: PMC6559361] [PubMed: 29887379]
    366.
    Maag J.L.V. et al. (2015) Dynamic expression of long noncoding RNAs and repeat elements in synaptic plasticity. Frontiers in Neuroscience 9: 351. [PMC free article: PMC4589673] [PubMed: 26483626]
    367.
    Bernard D. et al. (2010) A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO Journal 29: 3082–3093. [PMC free article: PMC2944070] [PubMed: 20729808]
    368.
    Barry G. et al. (2014) The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Molecular Psychiatry 19: 486–494. [PubMed: 23628989]
    369.
    Ip J.Y. et al. (2016) Gomafu lncRNA knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine. Scientific Reports 6: 27204. [PMC free article: PMC4890022] [PubMed: 27251103]
    370.
    Barry G. et al. (2017) The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states. Scientific Reports 7: 40127. [PMC free article: PMC5214838] [PubMed: 28054653]
    371.
    Butler A.A., Johnston D.R., Kaur S. and Lubin F.D. (2019) Long noncoding RNA NEAT1 mediates neuronal histone methylation and age-related memory impairment. Science Signaling 12: eaaw9277. [PMC free article: PMC7219525] [PubMed: 31266852]
    372.
    Kukharsky M.S. et al. (2020) Long non-coding RNA Neat1 regulates adaptive behavioural response to stress in mice. Translational Psychiatry 10: 171. [PMC free article: PMC7256041] [PubMed: 32467583]
    373.
    Xu H. et al. (2020) Role of long noncoding RNA Gas5 in cocaine action. Biological Psychiatry 88: 758–766. [PMC free article: PMC7584769] [PubMed: 32711952]
    374.
    Volff J.N. and Brosius J. (2007) Modern genomes with retro-look: Retrotransposed elements, retroposition and the origin of new genes. Gene and Protein Evolution 3: 175–190. [PubMed: 18753792]
    375.
    Centonze D. et al. (2007) The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum. Journal of Neuroscience 27: 8885–8892. [PMC free article: PMC6672174] [PubMed: 17699670]
    376.
    Zalfa F. et al. (2003) The Fragile X Syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses. Cell 112: 317–327. [PubMed: 12581522]
    377.
    Lewejohann L. et al. (2004) Role of a neuronal small non-messenger RNA: Behavioural alterations in BC1 RNA-deleted mice. Behavioural Brain Research 154: 273–289. [PubMed: 15302134]
    378.
    Chung A., Dahan N., Alarcon J.M. and Fenton A.A. (2017) Effects of regulatory BC1 RNA deletion on synaptic plasticity, learning, and memory. Learning & Memory 24: 646–649. [PMC free article: PMC5688958] [PubMed: 29142061]
    379.
    Labonté B. et al. (2021) Regulation of impulsive and aggressive behaviours by a novel lncRNA. Molecular Psychiatry 26: 3751–3764. [PMC free article: PMC7436429] [PubMed: 31907380]
    380.
    Issler O. et al. (2020) Sex-specific role for the long non-coding RNA LINC00473 in depression. Neuron 106: 912–926. [PMC free article: PMC7305959] [PubMed: 32304628]
    381.
    Tan M.C. et al. (2017) The activity-induced long non-coding RNA Meg3 modulates AMPA receptor surface expression in primary cortical neurons. Frontiers in Cellular Neuroscience 11: 124. [PMC free article: PMC5413565] [PubMed: 28515681]
    382.
    Anguera M.C. et al. (2011) Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain. PLOS Genetics 7: e1002248. [PMC free article: PMC3164691] [PubMed: 21912526]
    383.
    Li D. et al. (2018) Activity dependent LoNA regulates translation by coordinating rRNA transcription and methylation. Nature Communications 9: 1726. [PMC free article: PMC5928123] [PubMed: 29712923]
    384.
    Ma M. et al. (2020) A novel pathway regulates social hierarchy via lncRNA AtLAS and postsynaptic synapsin IIb. Cell Research 30: 105–118. [PMC free article: PMC7015055] [PubMed: 31959917]
    385.
    Zhang X., X.U. Yn, Chen B. and Kang L. (2020) Long noncoding RNA PAHAL modulates locust behavioural plasticity through the feedback regulation of dopamine biosynthesis. PLOS Genetics 16: e1008771. [PMC free article: PMC7241820] [PubMed: 32348314]
    386.
    Liu F. et al. (2019) lncRNA profile of Apis mellifera and its possible role in behavioural transition from nurses to foragers. BMC Genomics 20: 393. [PMC free article: PMC6528240] [PubMed: 31113365]
    387.
    Levenson J.M. and Sweatt J.D. (2005) Epigenetic mechanisms in memory formation. Nature Reviews Neuroscience 6: 108–118. [PubMed: 15654323]
    388.
    Graff J. and Mansuy I.M. (2008) Epigenetic codes in cognition and behaviour. Behavioural Brain Research 192: 70–87. [PubMed: 18353453]
    389.
    Jarome T.J. and Lubin F.D. (2014) Epigenetic mechanisms of memory formation and reconsolidation. Neurobiology of Learning and Memory 115: 116–127. [PMC free article: PMC4250295] [PubMed: 25130533]
    390.
    Marshall P. and Bredy T.W. (2016) Cognitive neuroepigenetics: The next evolution in our understanding of the molecular mechanisms underlying learning and memory? npj Science of Learning 1: 16014. [PMC free article: PMC4977095] [PubMed: 27512601]
    391.
    Pachter J.S., de Vries H.E. and Fabry Z. (2003) The blood-brain barrier and its role in immune privilege in the central nervous system. Journal of Neuropathology & Experimental Neurology 62: 593–604. [PubMed: 12834104]
    392.
    Banks W.A. and Erickson M.A. (2010) The blood–brain barrier and immune function and dysfunction. Neurobiology of Disease 37: 26–32. [PubMed: 19664708]
    393.
    Majerova P. et al. (2019) Trafficking of immune cells across the blood-brain barrier is modulated by neurofibrillary pathology in tauopathies. PLOS ONE 14: e0217216. [PMC free article: PMC6532920] [PubMed: 31120951]
    394.
    Crockett A.M. et al. (2020) Immune activation of the blood brain barrier and implications for neuroinflammation in schizophrenia. Journal of Immunology 204(1 Supplement): 158.23.
    395.
    Yoshihara Y., Oka S., Ikeda J. and Mori K. (1991) Immunoglobulin superfamily molecules in the nervous system. Neuroscience Research 10: 83–105. [PubMed: 1710044]
    396.
    Martin M.U. and Wesche H. (2002) Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochimica et Biophysica Acta 1592: 265–280. [PubMed: 12421671]
    397.
    Rougon G. and Hobert O. (2003) New insights into the diversity and function of neuronal immunoglobulin superfamily molecules. Annual Review of Neuroscience 26: 207–238. [PubMed: 12598678]
    398.
    Steinman L. (2004) Elaborate interactions between the immune and nervous systems. Nature Immunology 5: 575–581. [PubMed: 15164017]
    399.
    Maness P.F. and Schachner M. (2007) Neural recognition molecules of the immunoglobulin superfamily: Signaling transducers of axon guidance and neuronal migration. Nature Neuroscience 10: 19–26. [PubMed: 17189949]
    400.
    Zinn K. and Özkan E. (2017) Neural immunoglobulin superfamily interaction networks. Current Opinion in Neurobiology 45: 99–105. [PMC free article: PMC5554755] [PubMed: 28558267]
    401.
    Morimoto K. and Nakajima K. (2019) Role of the immune system in the development of the central nervous system. Frontiers in Neuroscience 13: 916. [PMC free article: PMC6735264] [PubMed: 31551681]
    402.
    Anthoney N., Foldi I. and Hidalgo A. (2018) Toll and Toll-like receptor signalling in development. Development 145: dev156018. [PubMed: 29695493]
    403.
    Chen C.-Y., Shih Y.-C., Hung Y.-F. and Hsueh Y.-P. (2019) Beyond defense: Regulation of neuronal morphogenesis and brain functions via Toll-like receptors. Journal of Biomedical Science 26: 90. [PMC free article: PMC6827257] [PubMed: 31684953]
    404.
    Foldi I. et al. (2017) Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila. Journal of Cell Biology 216: 1421–1438. [PMC free article: PMC5412559] [PubMed: 28373203]
    405.
    Paemen L.R. et al. (1992) Glial localization of interleukin-1α in invertebrate ganglia. Cellular and Molecular Neurobiology 12: 463–472. [PubMed: 1468116]
    406.
    Galic M.A., Riazi K. and Pittman Q.J. (2012) Cytokines and brain excitability. Frontiers in Neuroendocrinology 33: 116–125. [PMC free article: PMC3547977] [PubMed: 22214786]
    407.
    Miller A.H., Haroon E., Raison C.L. and Felger J.C. (2013) Cytokine targets in the brain: Impact on neurotransmitters and neurocircuits. Depression and Anxiety 30: 297–306. [PMC free article: PMC4141874] [PubMed: 23468190]
    408.
    Chun J.J.M., Schatz D.G., Oettinger M.A., Jaenisch R. and Baltimore D. (1991) The recombination activating gene-1 (RAG-1) transcript is present in the murine central nervous system. Cell 64: 189–200. [PubMed: 1986864]
    409.
    Fugmann S.D., Lee A.I., Shockett P.E., Villey I.J. and Schatz D.G. (2000) The RAG proteins and V(D)J recombination: Complexes, ends, and transposition. Annual Review of Immunology 18: 495–527. [PubMed: 10837067]
    410.
    Jessen J.R., Jessen T.N., Vogel S.S. and Lin S. (2001) Concurrent expression of recombination activating genes 1 and 2 in zebrafish olfactory sensory neurons. Genesis 29: 156–162. [PubMed: 11309848]
    411.
    Álvarez-Lindo N., Baleriola J., de los Ríos V., Suárez T. and de la Rosa E.J. (2019) RAG-2 deficiency results in fewer phosphorylated histone H2AX foci, but increased retinal ganglion cell death and altered axonal growth. Scientific Reports 9: 18486. [PMC free article: PMC6898044] [PubMed: 31811168]
    412.
    Abarrategui I. and Krangel M.S. (2007) Noncoding transcription controls downstream promoters to regulate T-cell receptor alpha recombination. EMBO Journal 26: 4380–4390. [PMC free article: PMC2034674] [PubMed: 17882258]
    413.
    Storici F., Bebenek K., Kunkel T.A., Gordenin D.A. and Resnick M.A. (2007) RNA-templated DNA repair. Nature 447: 338–341. [PMC free article: PMC2121219] [PubMed: 17429354]
    414.
    Nowacki M. et al. (2007) RNA-mediated epigenetic programming of a genome-rearrangement pathway. Nature 451: 153–158. [PMC free article: PMC2647009] [PubMed: 18046331]
    415.
    McGowan P.O., Hope T.A., Meck W.H., Kelsoe G. and Williams C.L. (2011) Impaired social recognition memory in recombination activating gene 1-deficient mice. Brain Research 1383: 187–195. [PMC free article: PMC3436067] [PubMed: 21354115]
    416.
    Matthews A.G. et al. (2007) RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature 450: 1106–1110. [PMC free article: PMC2988437] [PubMed: 18033247]
    417.
    Lee M.-H. et al. (2018) Somatic APP gene recombination in Alzheimer’s disease and normal neurons. Nature 563: 639–645. [PMC free article: PMC6391999] [PubMed: 30464338]
    418.
    Kaeser G. and Chun J. (2020) Brain cell somatic gene recombination and its phylogenetic foundations. Journal of Biological Chemistry 295: 12786–12795. [PMC free article: PMC7476723] [PubMed: 32699111]
    419.
    Eyman M. et al. (2007) Local synthesis of axonal and presynaptic RNA in squid model systems. European Journal of Neuroscience 25: 341–350. [PubMed: 17284174]
    420.
    Sotelo J.R. et al. (2014) Glia to axon RNA transfer. Developmental Neurobiology 74: 292–302. [PubMed: 23997031]
    421.
    Kiebler M.A. and Bassell G.J. (2006) Neuronal RNA granules: Movers and makers. Neuron 51: 685–690. [PubMed: 16982415]
    422.
    Carson J.H. et al. (2008) Multiplexed RNA trafficking in oligodendrocytes and neurons. Biochimica et Biophysica Acta 1779: 453–458. [PMC free article: PMC2584806] [PubMed: 18442491]
    423.
    Garner C.C., Tucker R.P. and Matus A. (1988) Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites. Nature 336: 674–677. [PubMed: 3200318]
    424.
    Burgin K.E. et al. (1990) In situ hybridization histochemistry of Ca2+/calmodulin-dependent protein kinase in developing rat brain. Journal of Neuroscience 10: 1788–1798. [PMC free article: PMC6570308] [PubMed: 2162385]
    425.
    Kanai Y., Dohmae N. and Hirokawa N. (2004) Kinesin transports RNA: Isolation and characterization of an RNA-transporting granule. Neuron 43: 513–525. [PubMed: 15312650]
    426.
    Hirokawa N. (2006) mRNA transport in dendrites: RNA granules, motors, and tracks. Journal of Neuroscience 26: 7139–7142. [PMC free article: PMC6673940] [PubMed: 16822968]
    427.
    Bramham C.R. and Wells D.G. (2007) Dendritic mRNA: Transport, translation and function. Nature Reviews Neuroscience 8: 776–789. [PubMed: 17848965]
    428.
    Yoon Y.J. et al. (2016) Glutamate-induced RNA localization and translation in neurons. Proceedings of the National Academy of Sciences USA 113: E6877–86. [PMC free article: PMC5098659] [PubMed: 27791158]
    429.
    Terenzio M., Schiavo G. and Fainzilber M. (2017) Compartmentalized signaling in neurons: From cell biology to neuroscience. Neuron 96: 667–679. [PubMed: 29096079]
    430.
    Madugalle S.U., Meyer K., Wang D.O. and Bredy T.W. (2020) RNA N6-methyladenosine and the regulation of RNA localization and function in the brain. Trends in Neurosciences 43: 1011–1023. [PMC free article: PMC7688512] [PubMed: 33041062]
    431.
    Raveendra B.L. et al. (2018) Long noncoding RNA GM12371 acts as a transcriptional regulator of synapse function. Proceedings of the National Academy of Sciences USA 115: E10197–205. [PMC free article: PMC6205475] [PubMed: 30297415]
    432.
    Grinman E. et al. (2021) Activity-regulated synaptic targeting of lncRNA ADEPTR mediates structural plasticity by localizing Sptn1 and AnkB in dendrites. Science Advances 7: eabf0605. [PMC free article: PMC8051873] [PubMed: 33863727]
    433.
    Wang F. et al. (2021) The long noncoding RNA Synage regulates synapse stability and neuronal function in the cerebellum. Cell Death & Differentiation 28: 2634–2650. [PMC free article: PMC8408218] [PubMed: 33762741]
    434.
    Liau W.-S., Samaddar S., Banerjee S. and Bredy T.W. (2021) On the functional relevance of spatiotemporally-specific patterns of experience-dependent long noncoding RNA expression in the brain. RNA Biology 18: 1025–1036. [PMC free article: PMC8216188] [PubMed: 33397182]
    435.
    McCurry C.L. et al. (2010) Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation. Nature Neuroscience 13: 450–457. [PMC free article: PMC2864583] [PubMed: 20228806]
    436.
    Guzowski J.F. et al. (2000) Inhibition of activity-dependent Arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. Journal of Neuroscience 20: 3993–4001. [PMC free article: PMC6772617] [PubMed: 10818134]
    437.
    Plath N. et al. (2006) Arc/Arg3.1 Is essential for the consolidation of synaptic plasticity and memories. Neuron 52: 437–444. [PubMed: 17088210]
    438.
    Pastuzyn E.D. et al. (2018) The neuronal gene Arc encodes a repurposed retrotransposon Gag protein that mediates intercellular RNA transfer. Cell 172: 275–288. [PMC free article: PMC5884693] [PubMed: 29328916]
    439.
    Ashraf S.I., McLoon A.L., Sclarsic S.M. and Kunes S. (2006) Synaptic protein synthesis associated with memory is regulated by the RISC pathway in Drosophila. Cell 124: 191–205. [PubMed: 16413491]
    440.
    Moazed D. (2012) A piRNA to remember. Cell 149: 512–514. [PubMed: 22541425]
    441.
    Ghosheh Y. et al. (2016) Characterization of piRNAs across postnatal development in mouse brain. Scientific Reports 6: 25039. [PMC free article: PMC4844963] [PubMed: 27112104]
    442.
    Huang X. and Wong G. (2021) An old weapon with a new function: PIWI-interacting RNAs in neurodegenerative diseases. Translational Neurodegeneration 10: 9. [PMC free article: PMC7938595] [PubMed: 33685517]
    443.
    Perrat P.N. et al. (2013) Transposition-driven genomic heterogeneity in the Drosophila brain. Science 340: 91–95. [PMC free article: PMC3887341] [PubMed: 23559253]
    444.
    Nandi S. et al. (2016) Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain. Proceedings of the National Academy of Sciences USA 113: 12697–12702. [PMC free article: PMC5111663] [PubMed: 27791114]
    445.
    Knowles R.B. et al. (1996) Translocation of RNA granules in living neurons. Journal of Neuroscience 16: 7812–7820. [PMC free article: PMC6579227] [PubMed: 8987809]
    446.
    Doyle M. and Kiebler M.A. (2011) Mechanisms of dendritic mRNA transport and its role in synaptic tagging. EMBO Journal 30: 3540–3552. [PMC free article: PMC3181491] [PubMed: 21878995]
    447.
    Das S., Singer R.H. and Yoon Y.J. (2019) The travels of mRNAs in neurons: Do they know where they are going? Current Opinion in Neurobiology 57: 110–116. [PMC free article: PMC6650148] [PubMed: 30784978]
    448.
    Dubnau J. et al. (2003) The staufen/pumilio pathway is involved in Drosophila long-term memory. Current Biology 13: 286–296. [PubMed: 12593794]
    449.
    Lucas B.A. et al. (2018) Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay. Proceedings of the National Academy of Sciences USA 115: 968–973. [PMC free article: PMC5798355] [PubMed: 29339519]
    450.
    Kim T.-K. et al. (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465: 182–187. [PMC free article: PMC3020079] [PubMed: 20393465]
    451.
    Wu W. et al. (2021) Neuronal enhancers are hotspots for DNA single-strand break repair. Nature 593: 440–444. [PMC free article: PMC9827709] [PubMed: 33767446]
    452.
    Wei P.-C. et al. (2016) Long neural genes harbor recurrent DNA break clusters in neural stem/progenitor cells. Cell 164: 644–655. [PMC free article: PMC4752721] [PubMed: 26871630]
    453.
    Reid D.A. et al. (2021) Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons. Science 372: 91–94. [PMC free article: PMC9179101] [PubMed: 33795458]
    454.
    Suberbielle E. et al. (2013) Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β. Nature Neuroscience 16: 613–621. [PMC free article: PMC3637871] [PubMed: 23525040]
    455.
    Stott R.T., Kritsky O. and Tsai L.-H. (2021) Profiling DNA break sites and transcriptional changes in response to contextual fear learning. PLOS ONE 16: e0249691. [PMC free article: PMC8248687] [PubMed: 34197463]
    456.
    Madabhushi R. et al. (2015) Activity-induced DNA breaks govern the expression of neuronal early-response genes. Cell 161: 1592–1605. [PMC free article: PMC4886855] [PubMed: 26052046]
    457.
    Lou M.-M. et al. (2021) Long noncoding RNA BS-DRL1 modulates the DNA damage response and genome stability by interacting with HMGB1 in neurons. Nature Communications 12: 4075. [PMC free article: PMC8249382] [PubMed: 34210972]
    458.
    Li X. et al. (2019) The DNA repair-associated protein gadd45γ regulates the temporal coding of immediate early gene expression within the prelimbic prefrontal cortex and is required for the consolidation of associative fear memory. Journal of Neuroscience 39: 970–983. [PMC free article: PMC6363930] [PubMed: 30545945]
    459.
    Chow H. and Herrup K. (2015) Genomic integrity and the ageing brain. Nature Reviews Neuroscience 16: 672–684. [PubMed: 26462757]
    460.
    Meers C. et al. (2020) Genetic characterization of three distinct mechanisms supporting RNA-driven DNA repair and modification reveals major role of DNA polymerase ζ. Molecular Cell 79: 1037–1050. [PMC free article: PMC7502545] [PubMed: 32882183]
    461.
    Chandramouly G. et al. (2021) Polθ reverse transcribes RNA and promotes RNA-templated DNA repair. Science Advances 7: eabf1771. [PMC free article: PMC8195485] [PubMed: 34117057]
    462.
    Chan K.Y., Li X., Ortega J., Gu L. and Li G.-M. (2021) DNA polymerase θ promotes CAG•CTG repeat expansions in Huntington’s disease via insertion sequences of its catalytic domain. Journal of Biological Chemistry 297: 101144. [PMC free article: PMC8463855] [PubMed: 34473992]
    463.
    Grishok A., Tabara H. and Mello C.C. (2000) Genetic requirements for inheritance of RNAi in C. elegans. Science 287: 2494–2497. [PubMed: 10741970]
    464.
    Kennerdell J.R. and Carthew R.W. (2000) Heritable gene silencing in Drosophila using double-stranded RNA. Nature Biotechnology 18: 896–898. [PubMed: 10932163]
    465.
    Vastenhouw N.L. et al. (2006) Gene expression: Long-term gene silencing by RNAi. Nature 442: 882. [PubMed: 16929289]
    466.
    Ashe A. et al. (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150: 88–99. [PMC free article: PMC3464430] [PubMed: 22738725]
    467.
    Grentzinger T. et al. (2012) piRNA-mediated transgenerational inheritance of an acquired trait. Genome Research 22: 1877–1888. [PMC free article: PMC3460183] [PubMed: 22555593]
    468.
    Shirayama M. et al. (2012) piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell 150: 65–77. [PMC free article: PMC3597741] [PubMed: 22738726]
    469.
    Lewis A. et al. (2020) A family of Argonaute-interacting proteins gates nuclear RNAi. Molecular Cell 78: 862–875. [PMC free article: PMC7613089] [PubMed: 32348780]
    470.
    Jones L., Ratcliff F. and Baulcombe D.C. (2001) RNA-directed transcriptional gene silencing in plants can be inherited independently of the RNA trigger and requires Met1 for maintenance. Current Biology 11: 747–757. [PubMed: 11378384]
    471.
    Bateson W. and Pellew C. (1920) The genetics of “rogues” among culinary peas (Pisum sativum). Proceedings of The Royal Society B: Biological Sciences 91: 186–195.
    472.
    Brink R.A. (1956) A genetic change associated with the R locus in maize which is directed and potentially reversible. Genetics 41: 872–889. [PMC free article: PMC1224369] [PubMed: 17247669]
    473.
    Brink R.A. (1958) Paramutation at the R locus in maize. Cold Spring Harbor Symposia on Quantitative Biology 23: 379–391. [PubMed: 13635569]
    474.
    Brink R.A., Styles E.D. and Axtell J.D. (1968) Paramutation: Directed genetic change. Science 159: 161–170. [PubMed: 5634904]
    475.
    Chandler V.L. (2007) Paramutation: From maize to mice. Cell 128: 641–645. [PubMed: 17320501]
    476.
    Pilu R. (2015) Paramutation phenomena in plants. Seminars in Cell & Developmental Biology 44: 2–10. [PubMed: 26335267]
    477.
    Hollick J.B. (2017) Paramutation and related phenomena in diverse species. Nature Reviews Genetics 18: 5–23. [PubMed: 27748375]
    478.
    Conine C.C. and Rando O.J. (2021) Soma-to-germline RNA communication. Nature Reviews Genetics 23: 73–88. [PubMed: 34545247]
    479.
    Bošković A. and Rando O.J. (2018) Transgenerational epigenetic inheritance. Annual Review of Genetics 52: 21–41. [PubMed: 30160987]
    480.
    Casier K., Boivin A., Carré C. and Teysset L. (2019) Environmentally-induced transgenerational epigenetic inheritance: Implication of PIWI interacting RNAs. Cells 8: 1108. [PMC free article: PMC6770481] [PubMed: 31546882]
    481.
    Zhao M. et al. (2021) The mop1 mutation affects the recombination landscape in maize. Proceedings of the National Academy of Sciences USA 118: e2009475118. [PMC free article: PMC7896300] [PubMed: 33558228]
    482.
    Rassoulzadegan M. et al. (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441: 469–474. [PubMed: 16724059]
    483.
    Pilu R. (2011) Paramutation: Just a curiosity or fine tuning of gene expression in the next generation? Current Genomics 12: 298–306. [PMC free article: PMC3131737] [PubMed: 22131875]
    484.
    Houri-Zeevi L., Korem Kohanim Y., Antonova O. and Rechavi O. (2020) Three rules explain transgenerational small RNA inheritance in C. elegans. Cell 182: 1186–1197. [PMC free article: PMC7479518] [PubMed: 32841602]
    485.
    Herman H. et al. (2003) Trans allele methylation and paramutation-like effects in mice. Nature Genetics 34: 199–202. [PMC free article: PMC2744043] [PubMed: 12740578]
    486.
    Watanabe T. et al. (2011) Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332: 848–852. [PMC free article: PMC3368507] [PubMed: 21566194]
    487.
    Sapetschnig A., Sarkies P., Lehrbach N.J. and Miska E.A. (2015) Tertiary siRNAs mediate paramutation in C. elegans. PLOS Genetics 11: e1005078. [PMC free article: PMC4374809] [PubMed: 25811365]
    488.
    Kiani J. et al. (2013) RNA–mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2. PLOS Genetics 9: e1003498. [PMC free article: PMC3662642] [PubMed: 23717211]
    489.
    Jeffreys A.J. (1987) Highly variable minisatellites and DNA fingerprints. Biochemical Society Transactions 15: 309–317. [PubMed: 2887471]
    490.
    Willems T. et al. (2014) The landscape of human STR variation. Genome Research 24: 1894–1904. [PMC free article: PMC4216929] [PubMed: 25135957]
    491.
    Quilez J. et al. (2016) Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans. Nucleic Acids Research 44: 3750–3762. [PMC free article: PMC4857002] [PubMed: 27060133]
    492.
    Gymrek M. (2017) A genomic view of short tandem repeats. Current Opinion in Genetics and Development 44: 9–16. [PubMed: 28213161]
    493.
    Hannan A.J. (2018) Tandem repeats mediating genetic plasticity in health and disease. Nature Reviews Genetics 19: 286–298. [PubMed: 29398703]
    494.
    Fondon III J.W., Hammock E.A.D., Hannan A.J. and King D.G. (2008) Simple sequence repeats: Genetic modulators of brain function and behavior. Trends in Neurosciences 31: 328–334. [PubMed: 18550185]
    495.
    Song J.H.T., Lowe C.B. and Kingsley D.M. (2018) Characterization of a human-specific tandem repeat associated with Bipolar Disorder and Schizophrenia. American Journal of Human Genetics 103: 421–430. [PMC free article: PMC6128321] [PubMed: 30100087]
    496.
    Fotsing S.F. et al. (2019) The impact of short tandem repeat variation on gene expression. Nature Genetics 51: 1652–1659. [PMC free article: PMC6917484] [PubMed: 31676866]
    497.
    Trost B. et al. (2020) Genome-wide detection of tandem DNA repeats that are expanded in autism. Nature 586: 80–86. [PMC free article: PMC9348607] [PubMed: 32717741]
    498.
    Mitra I. et al. (2021) Patterns of de novo tandem repeat mutations and their role in autism. Nature 589: 246–250. [PMC free article: PMC7810352] [PubMed: 33442040]
    499.
    Hannan A.J. (2021) Repeat DNA expands our understanding of autism spectrum disorder. Nature 589: 200–202. [PubMed: 33442037]
    500.
    Xu T. et al. (2021) Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene. Proceedings of the National Academy of Sciences USA 118: e2019043118. [PMC free article: PMC8256013] [PubMed: 34155099]
    501.
    Stam M., Belele C., Dorweiler J.E. and Chandler V.L. (2002) Differential chromatin structure within a tandem array 100 kb upstream of the maize b1 locus is associated with paramutation. Genes & Development 16: 1906–1918. [PMC free article: PMC186425] [PubMed: 12154122]
    502.
    Hannan A.J. (2010) Tandem repeat polymorphisms: Modulators of disease susceptibility and candidates for ‘missing heritability’. Trends in Genetics 26: 59–65. [PubMed: 20036436]
    503.
    Gymrek M. et al. (2016) Abundant contribution of short tandem repeats to gene expression variation in humans. Nature Genetics 48: 22–29. [PMC free article: PMC4909355] [PubMed: 26642241]
    504.
    Bennett S.T. et al. (1997) Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. Nature Genetics 17: 350–352. [PubMed: 9354805]
    505.
    Suzuki S., Miyabe E. and Inagaki S. (2018) Novel brain-expressed noncoding RNA, HSTR1, identified at a human-specific variable number tandem repeat locus with a human accelerated region. Biochemical and Biophysical Research Communications 503: 1478–1483. [PubMed: 30029879]
    506.
    Hauser M.T., Aufsatz W., Jonak C. and Luschnig C. (2011) Transgenerational epigenetic inheritance in plants. Biochimica et Biophysica Acta 1809: 459–468. [PMC free article: PMC4359895] [PubMed: 21515434]
    507.
    Chatterjee N., Lin Y., Santillan B.A., Yotnda P. and Wilson J.H. (2015) Environmental stress induces trinucleotide repeat mutagenesis in human cells. Proceedings of the National Academy of Sciences USA 112: 3764–3769. [PMC free article: PMC4378418] [PubMed: 25775519]
    508.
    Gouil Q. and Baulcombe D.C. (2018) Paramutation-like features of multiple natural epialleles in tomato. BMC Genomics 19: 203. [PMC free article: PMC5859443] [PubMed: 29554868]
    509.
    Anway M.D., Cupp A.S., Uzumcu M. and Skinner M.K. (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308: 1466–1469. [PubMed: 15933200]
    510.
    Franklin T.B. et al. (2010) Epigenetic transmission of the impact of early stress across generations. Biological Psychiatry 68: 408–415. [PubMed: 20673872]
    511.
    Crews D. et al. (2012) Epigenetic transgenerational inheritance of altered stress responses. Proceedings of the National Academy of Sciences USA 109: 9143–9148. [PMC free article: PMC3384163] [PubMed: 22615374]
    512.
    Dias B.G. and Ressler K.J. (2014) Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience 17: 89–96. [PMC free article: PMC3923835] [PubMed: 24292232]
    513.
    Liberman N., Wang S.Y. and Greer E.L. (2019) Transgenerational epigenetic inheritance: From phenomena to molecular mechanisms. Current Opinion in Neurobiology 59: 189–206. [PMC free article: PMC6889819] [PubMed: 31634674]
    514.
    Bozler J., Kacsoh B.Z. and Bosco G. (2019) Transgenerational inheritance of ethanol preference is caused by maternal NPF repression. eLife 8: e45391. [PMC free article: PMC6615861] [PubMed: 31287057]
    515.
    Pereira A.G., Gracida X., Kagias K. and Zhang Y. (2020) C. elegans aversive olfactory learning generates diverse intergenerational effects. Journal of Neurogenetics 34: 378–388. [PMC free article: PMC8034421] [PubMed: 32940103]
    516.
    Jung Y.H. et al. (2021) Recruitment of CTCF to an Fto enhancer is responsible for transgenerational inheritance of obesity. bioRxiv: 2020.11.20.391672. [PMC free article: PMC9897486] [PubMed: 36469784]
    517.
    Bodden C. et al. (2022) Intergenerational effects of a paternal Western diet during adolescence on offspring gut microbiota, stress reactivity, and social behavior. FASEB Journal 36: e21981. [PubMed: 34907601]
    518.
    Mohajer N., Joloya E.M., Seo J., Shioda T. and Blumberg B. (2021) Epigenetic transgenerational inheritance of the effects of obesogen exposure. Frontiers in Endocrinology 12: 1726. [PMC free article: PMC8716683] [PubMed: 34975759]
    519.
    Gapp K. et al. (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nature Neuroscience 17: 667–669. [PMC free article: PMC4333222] [PubMed: 24728267]
    520.
    Gapp K. et al. (2020) Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma. Molecular Psychiatry 25: 2162–2174. [PMC free article: PMC7473836] [PubMed: 30374190]
    521.
    Carpenter B.L. et al. (2018) Mother–child transmission of epigenetic information by tunable polymorphic imprinting. Proceedings of the National Academy of Sciences USA 115: E11970–7. [PMC free article: PMC6304996] [PubMed: 30509985]
    522.
    Carpenter B.L. et al. (2021) Oocyte age and preconceptual alcohol use are highly correlated with epigenetic imprinting of a noncoding RNA (nc886). Proceedings of the National Academy of Sciences USA 118: e2026580118. [PMC free article: PMC8000112] [PubMed: 33723081]
    523.
    Smemo S. et al. (2014) Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507: 371–375. [PMC free article: PMC4113484] [PubMed: 24646999]
    524.
    Ruud J. et al. (2019) The fat mass and obesity-associated protein (FTO) regulates locomotor responses to novelty via D2R medium spiny neurons. Cell Reports 27: 3182–3198. [PubMed: 31189104]
    525.
    Grandjean V. et al. (2015) RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders. Scientific Reports 5: 18193. [PMC free article: PMC4677355] [PubMed: 26658372]
    526.
    Sharma U. et al. (2016) Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science 351: 391–396. [PMC free article: PMC4888079] [PubMed: 26721685]
    527.
    Chen Q. et al. (2016) Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351: 397–400. [PubMed: 26721680]
    528.
    Zhang Y. et al. (2018) Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nature Cell Biology 20: 535–540. [PMC free article: PMC5926820] [PubMed: 29695786]
    529.
    Sarker G. et al. (2019) Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs. Proceedings of the National Academy of Sciences USA 116: 10547–10556. [PMC free article: PMC6534971] [PubMed: 31061112]
    530.
    Zhang Y., Shi J., Rassoulzadegan M., Tuorto F. and Chen Q. (2019) Sperm RNA code programmes the metabolic health of offspring. Nature Reviews Endocrinology 15: 489–498. [PMC free article: PMC6626572] [PubMed: 31235802]
    531.
    Skvortsova K., Iovino N. and Bogdanović O. (2018) Functions and mechanisms of epigenetic inheritance in animals. Nature Reviews Molecular Cell Biology 19: 774–790. [PubMed: 30425324]
    532.
    Bédécarrats A., Chen S., Pearce K., Cai D. and Glanzman D.L. (2018) RNA from trained Aplysia can induce an epigenetic engram for long-term sensitization in untrained Aplysia. eNeuro 5. doi: 10.1523/ENEURO.0038-18.2018. [PMC free article: PMC5962046] [PubMed: 29789810] [CrossRef]
    533.
    van Steenwyk G. et al. (2020) Involvement of circulating factors in the transmission of paternal experiences through the germline. EMBO Journal 39: e104579. [PMC free article: PMC7705452] [PubMed: 33034389]
    534.
    Burton N.O. et al. (2020) Cysteine synthases CYSL-1 and CYSL-2 mediate C. elegans heritable adaptation to P. vranovensis infection. Nature Communications 11: 1741. [PMC free article: PMC7142082] [PubMed: 32269224]
    535.
    Silver M.J. et al. (2015) Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Biology 16: 118. [PMC free article: PMC4464629] [PubMed: 26062908]
    536.
    Treppendahl M.B. et al. (2012) Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML. Blood 119: 206–216. [PMC free article: PMC3251229] [PubMed: 22058117]
    537.
    Romanelli V. et al. (2014) Variable maternal methylation overlapping the nc886/vtRNA2-1 locus is locked between hypermethylated repeats and is frequently altered in cancer. Epigenetics 9: 783–790. [PMC free article: PMC4063837] [PubMed: 24589629]
    538.
    Katzmarski N. et al. (2021) Transmission of trained immunity and heterologous resistance to infections across generations. Nature Immunology 22: 1382–1390. [PubMed: 34663978]
    539.
    Parrish N.F. et al. (2015) piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals. RNA 21: 1691–1703. [PMC free article: PMC4574747] [PubMed: 26283688]
    540.
    Hettema J.M., Annas P., Neale M.C., Kendler K.S. and Fredrikson M. (2003) A twin study of the genetics of fear conditioning. Archives of General Psychiatry 60: 702–708. [PubMed: 12860774]
    541.
    Loken E.K., Hettema J.M., Aggen S.H. and Kendler K.S. (2014) The structure of genetic and environmental risk factors for fears and phobias. Psychological Medicine 44: 2375–2384. [PMC free article: PMC4079768] [PubMed: 24384457]
    542.
    Grossniklaus U. et al. (2013) Transgenerational epigenetic inheritance: How important is it? Nature Reviews Genetics 14: 228–235. [PMC free article: PMC4066847] [PubMed: 23416892]
    543.
    Heard E. and Martienssen R.A. (2014) Transgenerational epigenetic inheritance: Myths and mechanisms. Cell 157: 95–109. [PMC free article: PMC4020004] [PubMed: 24679529]
    544.
    Horsthemke B. (2018) A critical view on transgenerational epigenetic inheritance in humans. Nature Communications 9: 2973. [PMC free article: PMC6065375] [PubMed: 30061690]
    545.
    Perez M.F. and Lehner B. (2019) Intergenerational and transgenerational epigenetic inheritance in animals. Nature Cell Biology 21: 143–151. [PubMed: 30602724]
    546.
    Bergmann M., Schindelmeiser J. and Greven H. (1984) The blood-testis barrier in vertebrates having different testicular organization. Cell and Tissue Research 238: 145–150.
    547.
    Mruk D.D. and Cheng C.Y. (2015) The mammalian blood-testis barrier: Its biology and regulation. Endocrine Reviews 36: 564–591. [PMC free article: PMC4591527] [PubMed: 26357922]

    Chapter 18

    1.
    Scherrer K. (2003) Historical review: The discovery of ‘giant’ RNA and RNA processing: 40 years of enigma. Trends in Biochemical Sciences 28: 566–571. [PubMed: 14559186]
    2.
    Niklas K.J. and Newman S.A. (2013) The origins of multicellular organisms. Evolution & Development 15: 41–52. [PubMed: 23331916]
    3.
    Niklas K.J. (2014) The evolutionary-developmental origins of multicellularity. American Journal of Botany 101: 6–25. [PubMed: 24363320]
    4.
    Darwin C. (1859) On the Origin of Species by Means of Natural Selection (John Murray, New York).
    5.
    Mattick J.S. (2009) Has evolution learnt how to learn? EMBO Reports 10: 665. [PMC free article: PMC2727432] [PubMed: 19568258]
    6.
    Barton R.A. and Venditti C. (2014) Rapid evolution of the cerebellum in humans and other great apes. Current Biology 24: 2440–2444. [PubMed: 25283776]
    7.
    Gould S.J. (1986) Evolution and the triumph of homology, or why history matters. American Scientist 74: 60–69.
    8.
    Gould S.J. (2004) The evolution of life on Earth. Scientific American SA Special Editions 14: 92–100.
    9.
    Blount Z.D., Lenski R.E. and Losos J.B. (2018) Contingency and determinism in evolution: Replaying life’s tape. Science 362: eaam5979. [PubMed: 30409860]
    10.
    Mattick J.S. (2007) A new paradigm for developmental biology. Journal of Experimental Biology 210: 1526–1547. [PubMed: 17449818]
    11.
    Amaral P.P., Dinger M.E., Mercer T.R. and Mattick J.S. (2008) The eukaryotic genome as an RNA machine. Science 319: 1787–1789. [PubMed: 18369136]
    12.
    Stoltzfus A. and Yampolsky L.Y. (2009) Climbing mount probable: Mutation as a cause of nonrandomness in evolution. Journal of Heredity 100: 637–647. [PubMed: 19625453]
    13.
    Baucom R.S. et al. (2009) Exceptional diversity, non-random distribution, and rapid evolution of retroelements in the Bw73 maize genome. PLOS Genetics 5: e1000732. [PMC free article: PMC2774510] [PubMed: 19936065]
    14.
    Martincorena I., Seshasayee A.S.N. and Luscombe N.M. (2012) Evidence of non-random mutation rates suggests an evolutionary risk management strategy. Nature 485: 95–98. [PubMed: 22522932]
    15.
    Martincorena I. and Luscombe N.M. (2013) Non-random mutation: The evolution of targeted hypermutation and hypomutation. BioEssays 35: 123–130. [PubMed: 23281172]
    16.
    Svensson E.I. and Berger D. (2019) The role of mutation bias in adaptive evolution. Trends in Ecology & Evolution 34: 422–434. [PubMed: 31003616]
    17.
    Storz J.F. et al. (2019) The role of mutation bias in adaptive molecular evolution: Insights from convergent changes in protein function. Philosophical Transactions of the Royal Society B: Biological Sciences 374: 20180238. [PMC free article: PMC6560279] [PubMed: 31154983]
    18.
    Monroe J.G. et al. (2022) Mutation bias reflects natural selection in Arabidopsis thaliana. Nature 602: 101–105. [PMC free article: PMC8810380] [PubMed: 35022609]
    19.
    Zhang J. (2022) Important genomic regions mutate less often than do other regions. Nature. News & Views: https://doi​.org/10.1038​/d41586-022-00017-6. [PubMed: 35022583]
    20.
    Downey R.G. and Fellows M.R. (1999) Parameterized Complexity (Springer, New York).
    21.
    Neumann F. and Sutton A.M. (2020) Parameterized complexity analysis of randomized search heuristics, in Doerr B. and Neumann F. (eds.) Theory of Evolutionary Computation: Recent Developments in Discrete Optimization (Springer, New York).
    22.
    Dennett D. (1995) Darwin’s Dangerous Idea: Evolution and the Meanings of Life (Simon Schuster, New York).
    23.
    Werner A., Piatek M.J. and Mattick J.S. (2015) Transpositional shuffling and quality control in male germ cells to enhance evolution of complex organisms. Annals of the New York Academy of Sciences 1341: 156–163. [PMC free article: PMC4390386] [PubMed: 25557795]
    24.
    Werner A. et al. (2021) Widespread formation of double-stranded RNAs in testis. Genome Research 31: 1174–1186. [PMC free article: PMC8256860] [PubMed: 34158368]
    25.
    Zhang W., Xie C., Ullrich K., Zhang Y.E. and Tautz D. (2021) The mutational load in natural populations is significantly affected by high primary rates of retroposition. Proceedings of the National Academy of Sciences USA 118: e2013043118. [PMC free article: PMC8017666] [PubMed: 33526666]
    26.
    Payne J.L. and Wagner A. (2019) The causes of evolvability and their evolution. Nature Reviews Genetics 20: 24–38. [PubMed: 30385867]
    27.
    Altenberg L. (1994) The evolution of evolvability in genetic programming, in K.E. Kinnear and P.J. Angeline (eds.) Advances in Genetic Programming (MIT Press, New York).
    28.
    Wagner G.P. and Altenberg L. (1996) Perspective: Complex adaptations and the evolution of evolvability. Evolution 50: 967–976. [PubMed: 28565291]
    29.
    Eiben A.E. and Smith J. (2015) From evolutionary computation to the evolution of things. Nature 521: 476–482. [PubMed: 26017447]
    30.
    Melo D., Porto A., Cheverud J.M. and Marroig G. (2016) Modularity: Genes, development and evolution. Annual Review of Ecology, Evolution, and Systematics 47: 463–486. [PMC free article: PMC5617135] [PubMed: 28966564]
    31.
    Espinosa-Soto C. (2018) On the role of sparseness in the evolution of modularity in gene regulatory networks. PLOS Computational Biology 14: e1006172. [PMC free article: PMC5979046] [PubMed: 29775459]
    32.
    Dellinger A.S. et al. (2019) Modularity increases rate of floral evolution and adaptive success for functionally specialized pollination systems. Communications Biology 2: 453. [PMC free article: PMC6895197] [PubMed: 31872071]
    33.
    Clune J., Mouret J.-B. and Lipson H. (2013) The evolutionary origins of modularity. Proceedings of the Royal Society B: Biological Sciences 280: 1–11. [PMC free article: PMC3574393] [PubMed: 23363632]
    34.
    Diaz-de-la-Loza M-d C., Loker R., Mann R.S. and Thompson B.J. (2020) Control of tissue morphogenesis by the HOX gene Ultrabithorax. Development 147: dev184564. [PMC free article: PMC7063672] [PubMed: 32122911]
    35.
    Kimura M. (1967) On the evolutionary adjustment of spontaneous mutation rates. Genetical Research 9: 23–34.
    36.
    Tenaillon O., Taddei F., Radman M. and Matic I. (2001) Second-order selection in bacterial evolution: Selection acting on mutation and recombination rates in the course of adaptation. Research in Microbiology 152: 11–16. [PubMed: 11281320]
    37.
    Sultana T., Zamborlini A., Cristofari G. and Lesage P. (2017) Integration site selection by retroviruses and transposable elements in eukaryotes. Nature Reviews Genetics 18: 292–308. [PubMed: 28286338]
    38.
    Duret L. (2009) Mutation patterns in the human genome: More variable than expected. PLOS Biology 7: e1000028. [PMC free article: PMC2634789] [PubMed: 19192948]
    39.
    Hodgkinson A. and Eyre-Walker A. (2011) Variation in the mutation rate across mammalian genomes. Nature Reviews Genetics 12: 756–766. [PubMed: 21969038]
    40.
    Supek F. and Lehner B. (2015) Differential DNA mismatch repair underlies mutation rate variation across the human genome. Nature 521: 81–84. [PMC free article: PMC4425546] [PubMed: 25707793]
    41.
    Harris K. and Pritchard J.K. (2017) Rapid evolution of the human mutation spectrum. eLife 6: e24284. [PMC free article: PMC5435464] [PubMed: 28440220]
    42.
    Castellano D., Eyre-Walker A. and Munch K. (2019) Impact of mutation rate and selection at linked sites on DNA variation across the genomes of humans and other homininae. Genome Biology and Evolution 12: 3550–3561. [PMC free article: PMC6944223] [PubMed: 31596481]
    43.
    Hawks J., Wang E.T., Cochran G.M., Harpending H.C. and Moyzis R.K. (2007) Recent acceleration of human adaptive evolution. Proceedings of the National Academy of Sciences USA 104: 20753–20758. [PMC free article: PMC2410101] [PubMed: 18087044]
    44.
    Jablonka E. and Lamb M. (1994) Epigenetic Inheritance and Evolution—The Lamarckian Dimension (Oxford University Press, New York).
    45.
    Jablonka E. and Lamb M.J. (1998) Epigenetic inheritance in evolution. Journal of Evolutionary Biology 11: 159–183.
    46.
    Jablonka E. (2012) Epigenetic variations in heredity and evolution. Clinical Pharmacology and Therapeutics 92: 683–688. [PubMed: 23073209]
    47.
    Jablonka E. (2017) The evolutionary implications of epigenetic inheritance. The Royal Society Interface Focus 7: 20160135. [PMC free article: PMC5566804] [PubMed: 28839916]
    48.
    Skinner M.K. (2015) Environmental epigenetics and a unified theory of the molecular aspects of evolution: A neo-Lamarckian concept that facilitates neo-Darwinian evolution. Genome Biology and Evolution 7: 1296–1302. [PMC free article: PMC4453068] [PubMed: 25917417]
    49.
    Drinnenberg I.A. et al. (2019) EvoChromo: Towards a synthesis of chromatin biology and evolution. Development 146: dev178962. [PMC free article: PMC7376748] [PubMed: 31558570]
    50.
    Ashe A., Colot V. and Oldroyd B.P. (2021) How does epigenetics influence the course of evolution? Philosophical Transactions of the Royal Society B: Biological Sciences 376: 20200111. [PMC free article: PMC8059608] [PubMed: 33866814]
    51.
    Melamed D. et al. (2022) De novo mutation rates at the single-mutation resolution in a human HBB gene-region associated with adaptation and genetic disease. Genome Research 32: 488–498. [PMC free article: PMC8896469] [PubMed: 35031571]
    52.
    Sharma S.V. et al. (2010) A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141: 69–80. [PMC free article: PMC2851638] [PubMed: 20371346]
    53.
    Planck M. (1949) Scientific Autobiography and Other Papers (Williams & Norgate, New York).
© 2023 John Mattick and Paulo Amaral.

Open Access: This content is Open Access under the Creative Commons license CC-BY-NC-ND.

Bookshelf ID: NBK595942

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