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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 08, 2017 |
| Title |
The nuclear RNA exosome is co-opted to enhance host:viral RNA hybrids that propel influenza virus ribogenesis and infectivity |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
The nuclear RNA exosome is an essential multi-subunit complex that controls RNA homeostasis. Congenital mutations in exosome genes are associated with neurodegenerative diseases. Here, we show that transient depletion of nuclear RNA exosome subunits in epithelial cells inhibits influenza virus replication. Similarly, viral biogenesis was suppressed in cells derived from mice with conditional ablation of the RNA exosome subunit Exosc3. Furthermore, patient-derived cells with a congenital EXOSC3 mutation were less susceptible to influenza virus infection. Using proteomics and next generation sequencing during infection, we show that the viral polymerase complex (PA, PB2, PB1) co-opts the nuclear RNA exosome complex and cellular RNAs en route to 3’ end degradation. Mechanistically, the nuclear RNA exosome coordinates the initial steps of viral transcription with RNAPII at host promoters. Exosome deficiency uncouples chromatin targeting of the viral polymerase complex and the formation of cellular:viral RNA hybrids, which are essential RNA intermediates that license transcription of antisense genomic viral RNAs. Overall, we discovered a critical nexus between an essential component of the influenza virus (polymerase) and an essential component of the cell (exosome), alteration of which leads to breakage of host-pathogen symmetry and a lose-lose scenario (viral impairment and neurodegeneration).
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| Overall design |
(1) Examination of influenza RNA levels in murine B cells conditionally ablated for the RNA exosome subunit Exosc3 (2) Examination of both host:viral chimeric mRNAs and the cellular transcriptome in human A549 cells transiently depleted for RNA exosome subunits DIS3 or EXOSC10; along with siRNA control (3) Examination of both host:viral chimeric mRNAs and the cellular transcriptome in human A549 cells transiently transfected with a plasmid encoding human DIS3 or an empty vector (EV) control
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| Contributor(s) |
Rialdi A, Hultquist J, Jimenez DM, Peralta Z, Campisi L, Fenouil R, Moshkina N, Wang ZZ, Laffleur B, Michael R, Haas K, Pefanis E, Albrecht RA, Pache L, Chanda S, Jen J, Byun M, Basu U, Garcia-Sastre A, Krogan N, van Bakel H, Marazzi I |
| Citation(s) |
28475896, 32559462 |
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| Submission date |
Mar 15, 2017 |
| Last update date |
Jul 07, 2020 |
| Contact name |
Zuleyma Peralta |
| E-mail(s) |
[email protected]
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| Phone |
212-824-9070
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Genetics and Genomic Sciences
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| Lab |
Bakel
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| Street address |
1470 Madison Ave Rm 8-302
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA379330 |
| SRA |
SRP101971 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE96677_RAW.tar |
4.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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