VIRMA mediates preferential m⁶A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation.

ABSTRACT: N⁶-methyladenosine (m⁶A) is enriched in 3'untranslated region (3'UTR) 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

SUBMITTER: Yue Y 

PROVIDER: S-EPMC5826926 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature