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

Abstract

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.

Keywords: Xist; alternative splicing/polyadenylation; mRNA export; mRNA stability; mRNA translation; sex lethal.