N6-methyladenosine modification in mRNA: machinery, function and implications for health and diseases

摘要

N6-methyladenosine (m(6)A) modification in mRNA is extremely widespread, and functionally modulates the eukaryotic transcriptome to influence mRNA splicing, export, localization, translation, and stability. Methylated adenines are present in a large subset of mRNAs and long noncoding RNAs (lncRNAs). Methylation is reversible, and this is accomplished by the orchestrated action of highly conserved methyltransferase (m(6)A writer) and demethylase (m(6)A eraser) enzymes to shape the cellular 'epitranscriptome'. The engraved 'methyl code' is subsequently decoded and executed by a group of m(6)A reader/effector components, which, in turn, govern the fate of the modified transcripts, thereby dictating their potential for translation. Reversible mRNA methylation thus adds another layer of regulation at the post-transcriptional level in the gene expression programme of eukaryotes that finely sculpts a highly dynamic proteome in order to respond to diverse cues during cellular differentiation, immune tolerance, and neuronal signalling.