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In eukaryotes, N6-methyladenosine (m6A) is an abundant modification in mRNAs and lncRNAs. m6A is also present in U6 snRNA introduced by METTL16 methyltransferase, although its molecular function and physiological role remain to be elucidated.
Through RNA-seq analysis of fission yeast METTL16 ortholog mtl16 knockout strain, we found a subset of introns retained in mRNAs, indicating that loss of m6A in U6 snRNA results in splicing defect. The affected introns were mainly those bearing an adenosine at the 4th position from the 5' splice site, which is faced against m6A of U6 snRNA recognizing 5' splice site in the spliceosome. In addition, the retained introns tend to bear sequences weakly recognized by U5 snRNA in the 3' end region of the 5' exons. These findings suggest a novel function of m6A involved in the splicing machinery, assisting the binding with U6 snRNA when an intron bears A at the 4th position, and has weak binding affinity to U5 snRNA. |