Settling the m⁶A 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 N⁶-methyladenosine (m⁶A) in RNA transcripts by analyzing different subcellular fractions. Using a recently developed biochemical approach for detecting m⁶A, the researchers show that m⁶A methylations are enriched in exons and are added to transcripts prior to splicing. Although m⁶A 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 m⁶A in mRNA biogenesis and function. Ke and colleagues found that m⁶A methylation levels negatively correlate with transcript half-life but are not required for most pre-mRNA splicing events.