N6-methyladenosine marks primary microRNAs for processing
作者： Claudio R. Alarcón , Hyeseung Lee , Hani Goodarzi , Nils Halberg , Sohail F. Tavazoie
DOI: 10.1038/NATURE14281
关键词: Cell biology 、 DGCR8 、 RNase P 、 Microprocessor complex 、 RNA 、 Drosha 、 MRNA modification 、 Molecular biology 、 RNA-binding protein 、 Regulation of gene expression 、 Biology
摘要: The first step in the biogenesis of microRNAs is processing primary (pri-miRNAs) by microprocessor complex, composed RNA-binding protein DGCR8 and type III RNase DROSHA. This initial event requires recognition junction between stem flanking single-stranded RNA pri-miRNA hairpin followed recruitment DROSHA, which cleaves duplex to yield pre-miRNA product. While mechanisms underlying have been determined, mechanism recognizes binds pri-miRNAs, as opposed other secondary structures present transcripts, not understood. Here we find mammalian cells that methyltransferase-like 3 (METTL3) methylates marking them for DGCR8. Consistent with this, METTL3 depletion reduced binding pri-miRNAs resulted global reduction mature miRNAs concomitant accumulation unprocessed pri-miRNAs. In vitro reactions confirmed sufficiency N(6)-methyladenosine (m(6)A) mark promoting processing. Finally, gain-of-function experiments revealed sufficient enhance miRNA maturation a non-cell-type-specific manner. Our findings reveal m(6)A acts key post-transcriptional modification promotes initiation biogenesis.
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