Multifaceted regulation of translation by the epitranscriptomic modification N6-methyladenosine.

Translation occurring on cytoplasmic mRNA is precisely governed at three consecutive stages, including initiation, elongation and termination. A growing body of evidence has revealed that an emerging epitranscriptomic code N⁶-methyladenosine (m⁶A), asymmetrically present in a large subset of coding and non-coding transcripts, is crucially required for mediating the translatomic stability. Through recruiting translation machinery proteins, serving as a physical barrier, or directing RNA structural rearrangement and mRNA looping formation, m⁶A has been decoded to modulate translational dynamics through potentially influencing the progress of different stages, thereby forming an additional layer of complexity to the regulation of translation. In this review, we summarize the current understanding of how m⁶A guides mRNA translation under normal and stress conditions, highlighting the divergent molecular mechanisms of multifarious regulation of m⁶A-mediated translation.