|
| Status |
Public on Mar 07, 2018 |
| Title |
VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
N6-methyadenosine (m6A) is enriched in 3`UTR (3` untranslated region) and near stop codon of mature polyadenylated mRNAs in mammalian systems and has regulatory roles in eukaryotic mRNA transcriptome switch. Significantly, the mechanism for this modification preference remains unknown, however. Herein we report a characterization of the full m6A methyltransferase complex in HeLa cells identifying METTL3/METTL14/WTAP/VIRMA/HAKAI/ZC3H13 as the key components, and we show that VIRMA mediates preferential mRNA methylation in 3`UTR and near stop codon. Biochemical studies reveal that VIRMA recruits the catalytic core components METTL3/METTL14/WTAP to guide region-selective methylations. Around 60% of VIRMA mRNA immunoprecipitation targets manifest strong m6A enrichment in 3`UTR. Depletions of VIRMA and METTL3 induce 3`UTR lengthening of several hundred mRNAs with over 50% targets in common. VIRMA associates with polyadenylation cleavage factors CPSF5 and CPSF6 in an RNA-dependent manner. Depletion of CPSF5 leads to significant shortening of 3`UTR of over 2,800 mRNAs, 84% of which are modified with m6A. Together our studies provide insights into m6A deposition specificity in 3`UTR and its correlation with alternative polyadenylation.
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| Overall design |
We used VIRMA KO/KD cell lines to test m6A deposition specificity in 3`UTR and its correlation with alternative polyadenylation.
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| Contributor(s) |
Yue Y, Liu J, Cui X, He C, Liu J |
| Citation(s) |
29507755 |
| |
| Submission date |
Aug 10, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Xiaolong Cui |
| E-mail(s) |
xiaolong.cui@northwestern.edu
|
| Organization name |
Northwestern University
|
| Department |
Department of Preventive Medicine
|
| Street address |
680 N Lake Shore Drive
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (60)
|
|
| Relations |
| BioProject |
PRJNA397879 |
| SRA |
SRP115202 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102493_Ctrl_PE_m6A.narrowPeak.gz |
219.1 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_Ctrl_m6A.narrowPeak.gz |
102.1 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_METTL14_Mut_peaks.narrowPeak.gz |
356.7 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_METTL3_Mut_peaks.narrowPeak.gz |
543.2 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_VIRMA_Mut_PE_m6A.narrowPeak.gz |
741.7 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_VIRMA_Mut_m6A.narrowPeak.gz |
162.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_Wild_Ctrl_peaks.narrowPeak.gz |
239.3 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_siCPSF5_m6A_peaks.narrowPeak.gz |
454.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_siCtrl_for_HAKAI_peaks.narrowPeak.gz |
593.1 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_siCtrl_for_VIRMA_m6A.narrowPeak.gz |
360.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_siCtrl_m6A_peaks.narrowPeak.gz |
680.8 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_siHAKAI_m6A_peaks.narrowPeak.gz |
505.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_siVIRMA_m6A.narrowPeak.gz |
437.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE102493_siZC3H13_m6A_peaks.narrowPeak.gz |
333.0 Kb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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