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 (m6 A) is the most prominent mRNA modification, and is installed by a large methyltransferase complex (the m6 A 'writer'), not only 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, 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 maximize gene expression. Additionally, m6 A appears to have a second function during developmental transitions by targeting m6 A-marked transcripts for degradation.