Acute depletion of METTL3 implicates <i>N</i> ⁶-methyladenosine in alternative intron/exon inclusion in the nascent transcriptome.

ABSTRACT: RNA N ⁶-methyladenosine (m⁶A) modification plays important roles in multiple aspects of RNA regulation. m⁶A is installed cotranscriptionally by the METTL3/14 complex, but its direct roles in RNA processing remain unclear. Here, we investigate the presence of m⁶A in nascent RNA of mouse embryonic stem cells. We find that around 10% of m⁶A peaks are located in alternative introns/exons, often close to 5' splice sites. m⁶A peaks significantly overlap with RBM15 RNA binding sites and the histone modification H3K36me3. Acute depletion of METTL3 disrupts inclusion of alternative introns/exons in the nascent transcriptome, particularly at 5' splice sites that are proximal to m⁶A peaks. For terminal or variable-len

SUBMITTER: Wei G 

PROVIDER: S-EPMC8327914 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature