Due to the role of m6A in alternative splicing, pre-mRNAs have higher levels of m6A than mature mRNAs. Moreover, m6A is more abundant in mRNAs that undergo alternative splicing compared to genes that code a single isoform. This is because alternatively spliced mRNAs are enriched in METTL3 binding sites. Splicing is affected in Mettl3 knock-out mice, resulting in increased frequency of exon skipping and intron retention. However, m6A is not a general unspecific splicing factor, it only participates in the alternative splicing of certain mRNAs and lncRNAs.
