Molecular Mechanisms Driving mRNA Degradation by m6A Modification.

N6-Methyladenosine (m6A), the most prevalent internal modification associated with eukaryotic mRNAs, influences many steps of mRNA metabolism, including splicing, export, and translation, as well as stability. Recent studies have revealed that m6A-containing mRNAs undergo one of two distinct pathways of rapid degradation: deadenylation via the YT521-B homology (YTH) domain-containing family protein 2 (YTHDF2; an m6A reader protein)-CCR4/NOT (deadenylase) complex or endoribonucleolytic cleavage by the YTHDF2-HRSP12-ribonuclease (RNase) P/mitochondrial RNA-processing (MRP) (endoribonuclease) complex. Some m6A-containing circular RNAs (circRNAs) are also subject to endoribonucleolytic cleavage by YTHDF2-HRSP12-RNase P/MRP. Here, we highlight recent progress on the molecular mechanisms underlying rapid mRNA degradation via m6A and describe our current understanding of the dynamic regulation of m6A-mediated mRNA decay through the crosstalk between m6A (or YTHDF2) and other cellular factors.