The RNA modification N6-methyladenosine (m6A) is found throughout the mRNA and can mediate its decay; however, how m6A at specific mRNA regions affects mRNA decay is unclear. Zhou et al. now describe a new mRNA decay pathway that depends on m6A at the mRNA coding sequence (CDS).

The CDS-specific effects indicated a link to translation. Indeed, translation inhibition stabilized mRNAs with m6A sites in the CDS, but not in the untranslated regions, in an m6A-dependent manner. Furthermore, m6A depletion increased the expression of GFP protein fused in-frame to CDS-m6A mRNA fragments, but the increase was abolished by moving the stop codon upstream of the m6A sites. Thus, translation is important for CMD.