Novel RNA regulatory mechanisms revealed in the epitranscriptome

Methyl-6-adenosine (m(6)A) has been hypothesized to exist since the 1970s,(1) but little has been known about the specific RNAs, or sites within them, that are affected by this RNA modification. Here, we report that recent work has shown RNA modifications like m(6)A, collectively called the “epitranscriptome,” are a pervasive feature of mammalian cells and likely play a role in development and disease. An enrichment of m(6)A near the last CDS of thousands of genes has implicated m(6)A in transcript processing, translational regulation and potentially a mechanism for regulating miRNA maturation. Also, because the sites of m(6)A show strong evolutionary conservation and have been replicated in nearly identical sites between mouse and human, strong evolutionary pressures are likely being maintained for this mark.(2)(,)(3) Finally, we note that m(6)A is one of over 100 modifications of RNA that have been reported,(4) and with the combination of high-throughput, next-generation sequencing (NGS) techniques, immunoprecipitation with appropriate antibodies and splicing-aware peak-finding, the dynamics of the epitranscriptome can now be mapped and characterized to discern their specific cellular roles.