Readers, writers and erasers of N⁶-methylated adenosine modification

N⁶-methyladenosine (m⁶A) as the most prevalent internal modification in mammalian RNAs has been increasingly realized as an important reversible mark that participates in various biological processes and cancer pathogenesis. In this review, we discuss the catalytic mechanisms of MT-A70 domain family proteins for mediating adenosine N⁶-methylation, the removal of this RNA mark by members of ALKB homologue domain family proteins, and the recognition of these m⁶A-modified RNAs by YTH domain family proteins. Our discussions focus on the recent advances in our understandings of the structural and functional properties of N⁶-methyladenosine methyltransferases, demethylases and reader proteins. Overall, we aim to mechanistically explain the reversible and dynamic nature of this unique RNA internal modification that contributes to the complexity of RNA-mediated gene regulation, and inspire new studies in epitranscriptomics.