m 6 A in mRNA: An Ancient Mechanism for Fine-Tuning Gene Expression

Modifications in mRNA constitute ancient mechanisms to regulate gene expression post-transcriptionally. N6-methyladenosine (m6A) is the most prominent mRNA modification, and is installed by a large methyltransferase complex (the m6A 'writer'), not only specifically bound by RNA-binding proteins (the m6A 'readers'), but also removed by demethylases (the m6A 'erasers'). m6A mRNA modifications have been linked to regulation at multiple steps in mRNA processing. In analogy to the regulation of gene expression by miRNAs, we propose that the main function of m6A is post-transcriptional fine-tuning of gene expression. In contrast to miRNA regulation, which mostly reduces gene expression, we argue that m6A provides a fast mean to post-transcriptionally maximize gene expression. Additionally, m6A appears to have a second function during developmental transitions by targeting m6A-marked transcripts for degradation.