Settling the m(6)A debate: methylation of mature mRNA is not dynamic but accelerates turnover

Post-transcriptional modification of RNA nucleosides has been implicated as a pivotal regulator of mRNA biology. In this issue of Genes & Development, Ke and colleagues (pp. 990–1006) provide insights into the temporal and spatial distribution of N(6)-methyladenosine (m(6)A) in RNA transcripts by analyzing different subcellular fractions. Using a recently developed biochemical approach for detecting m(6)A, the researchers show that m(6)A methylations are enriched in exons and are added to transcripts prior to splicing. Although m(6)A addition is widely thought to be readily reversible, they demonstrate in HeLa cells that once RNA is released from chromatin, the modifications are surprisingly static. This study integrates data from previous publications to clarify conflicting conclusions regarding the role of m(6)A in mRNA biogenesis and function. Ke and colleagues found that m(6)A methylation levels negatively correlate with transcript half-life but are not required for most pre-mRNA splicing events.