Abstract
RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N(6) -methyladenosine (m(6) A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m(6) A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre-mRNA processing, nuclear export, decay, and translation. The importance of m(6) A methylation as a mode of post-transcriptional gene expression regulation is evident in the crucial roles m(6) A-mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m(6) A exerts its functions and discuss recent advances that underscore the multifaceted role of m(6) A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m(6) A deposition on mRNA and its context-dependent effects on mRNA decay and translation, the role of m(6) A methylation of non-coding chromosomal-associated RNA species in regulating transcription, and the activities of the RNA demethylase FTO on diverse substrates. We also discuss emerging evidence for the therapeutic potential of targeting m(6) A regulators in disease.