RT Journal
A1 Wei, Guifeng
A1 Almeida, Mafalda
A1 Pintacuda, Greta
A1 Coker, Heather
A1 Bowness, Joseph S.
A1 Ule, Jernej
A1 Brockdorff, Neil
T1 Acute depletion of METTL3 implicates N6-methyladenosine in alternative intron/exon inclusion in the nascent transcriptome
JF Genome Research 
JO Genome Research 
YR 2021 
FD August 01 
VO 31 
IS 8 
SP 1395 
OP 1408 
DO 10.1101/gr.271635.120 
UL http://genome.cshlp.org/content/31/8/1395.abstract 
AB RNA N6-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-length exons, m6A peaks are generally located on or immediately downstream from a 5′ splice site that is suppressed in the presence of m6A and upstream of a 5′ splice site that is promoted in the presence of m6A. Genes with the most immediate effects on splicing include several components of the m6A pathway, suggesting an autoregulatory function. Collectively, our findings demonstrate crosstalk between the m6A machinery and the regulation of RNA splicing.