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Status |
Public on Oct 19, 2017 |
Title |
METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs |
Organism |
Homo sapiens |
Experiment type |
Other
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Summary |
N6-methyladenosine (m6A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m6A modifications are installed by the METTL3-METTL14 complex, others appear to be introduced independently, implying that additional human m6A methyltransferases remain to be identified. Using crosslinking and analysis of cDNA (CRAC), we reveal that the putative human m6A “writer” protein METTL16 binds to the U6 snRNA and other ncRNAs as well as numerous lncRNAs and pre-mRNAs. We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA and identify the early U6 biogenesis factors La, LARP7 and the methylphosphate capping enzyme MEPCE as METTL16-interaction partners. Interestingly, A43 lies within an essential ACAGAGA box of U6 that base pairs with 5’ splice sites of pre-mRNAs during splicing, suggesting that METTL16-mediated modification of this site plays an important role in splicing regulation. The identification of METTL16 as an active m6A methyltransferase in human cells expands our understanding of the mechanisms by which the m6A landscape is installed on cellular RNAs.
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Overall design |
HEK293 cell lines expressing His-FLAG-tagged human METTL16 or the His-FLAG tag alone were crosslinked using wavelengths of 254nm (UV-CRAC) or after 4-thiouridine incorporation 365nm (PAR-CRAC), and analysed by CRAC
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Contributor(s) |
Warda AS, Kretschmer J, Hackert P, Lenz C, Urlaub H, Höbartner C, Sloan KE, Bohnsack MT |
Citation(s) |
29051200 |
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Submission date |
Sep 18, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Markus T. Bohnsack |
E-mail(s) |
[email protected]
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Organization name |
Goettingen University
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Department |
Institute for Molecular Biology
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Street address |
Humboldtallee 23
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City |
Goettingen |
ZIP/Postal code |
37073 |
Country |
Germany |
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Platforms (1) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (6)
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Relations |
BioProject |
PRJNA407773 |
SRA |
SRP117925 |
Supplementary file |
Size |
Download |
File type/resource |
GSE103948_FlagPARsnRNAs.txt.gz |
94 b |
(ftp)(http) |
TXT |
GSE103948_FlagUVoverview.txt.gz |
141 b |
(ftp)(http) |
TXT |
GSE103948_FlagUVsnRNAs.txt.gz |
93 b |
(ftp)(http) |
TXT |
GSE103948_METTL16PARsnRNAs.txt.gz |
102 b |
(ftp)(http) |
TXT |
GSE103948_METTL16UVoverview.txt.gz |
150 b |
(ftp)(http) |
TXT |
GSE103948_METTL16UVsnRNAs.txt.gz |
102 b |
(ftp)(http) |
TXT |
GSE103948_METTL16lncRNAs.txt.gz |
1.8 Kb |
(ftp)(http) |
TXT |
GSE103948_METTL16mRNAs.txt.gz |
7.0 Kb |
(ftp)(http) |
TXT |
GSE103948_METTL16ncRNAs.txt.gz |
369 b |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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