m6A in mRNA: An ancient mechanism for fine-tuning gene expression

Modifications in messenger RNA (mRNA) constitute ancient mechanisms to regulate gene expression post-transcriptionally. N6 -methyladenosine (m6 A) is the most prominent mRNA modification, which is installed by a large methyltransferase complex (the m6 A ‘writer’), specifically bound by RNA binding proteins (the m6 A ‘readers), but also removed by demethylases (the m6 A ‘erasers’). m6 A mRNA modifications have been linked to regulation at multiple steps in mRNA processing. In analogy to the regulation of gene expression by miRNAs, 3 we propose that the main function of m6 A is post-transcriptional fine-tuning of gene expression. In contrast to miRNA regulation, which mostly reduces gene expression, we argue that m6 A provides a fast mean to post-transcriptionally maximise gene expression. Additionally, m6 A appears to have a second function during developmental transitions by targeting m6 A-marked transcripts for degradation.