m6A in mRNA: An Ancient Mechanism for Fine-Tuning Gene Expression

Modifications in mRNA constitute ancient mechanisms to regulate gene expression post-transcriptionally. N-6-methyladenosine (m(6)A) is the most prominent mRNA modification, and is installed by a large methyltransferase complex (the m(6)A 'writer'), not only specifically bound by RNA-binding proteins (the m(6)A 'readers'), but also removed by demethylases (the m(6)A 'erasers'). m(6)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 m(6)A is post-transcriptional fine-tuning of gene expression. In contrast to miRNA regulation, which mostly reduces gene expression, we argue that m(6)A provides a fast mean to post-transcriptionally maximize gene expression. Additionally, m(6)A appears to have a second function during developmental transitions by targeting m(6)A-marked transcripts for degradation.