Reading, writing and erasing mRNA methylation

Abstract

RNA methylation to form N⁶-methyladenosine (m⁶A) in mRNA accounts for the most abundant mRNA internal modification and has emerged as a widespread regulatory mechanism that controls gene expression in diverse physiological processes. Transcriptome-wide m⁶A mapping has revealed the distribution and pattern of m⁶A in cellular RNAs, referred to as the epitranscriptome. These maps have revealed the specific mRNAs that are regulated by m⁶A, providing mechanistic links connecting m⁶A to cellular differentiation, cancer progression and other processes. The effects of m⁶A on mRNA are mediated by an expanding list of m⁶A readers and m⁶A writer-complex components, as well as potential erasers that currently have unclear relevance to m⁶A prevalence in the transcriptome. Here we review new and emerging methods to characterize and quantify the epitranscriptome, and we discuss new concepts - in some cases, controversies - regarding our understanding of the mechanisms and functions of m⁶A readers, writers and erasers.