Reading, writing and erasing mRNA methylation

RNA methylation to form N-6-methyladenosine (m(6)A) 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 m(6)A mapping has revealed the distribution and pattern of m(6)A in cellular RNAs, referred to as the epitranscriptome. These maps have revealed the specific mRNAs that are regulated by m(6)A, providing mechanistic links connecting m(6)A to cellular differentiation, cancer progression and other processes. The effects of m(6)A on mRNA are mediated by an expanding list of m(6)A readers and m(6)A writer-complex components, as well as potential erasers that currently have unclear relevance to m(6)A 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 m(6)A readers, writers and erasers.