Hidden codes in mRNA: Control of gene expression by m⁶A

Information in mRNA has largely been thought to be confined to its nucleotide sequence. However, the advent of mapping techniques to detect modified nucleotides has revealed that mRNA contains additional information in the form of chemical modifications. The most abundant modified nucleotide is N⁶-methyladenosine (m⁶A), a methyl modification of adenosine. Although early studies viewed m⁶A as a dynamic and tissue-specific modification, it is now clear that the mRNAs that contain m⁶A and the location of m⁶A in those transcripts are largely universal and are influenced by gene architecture, i.e., the size and location of exons and introns. m⁶A can affect nuclear processes such as splicing and epigenetic regulation, but the major effect of m⁶A on mRNAs is to promote degradation in the cytoplasm. m⁶A marks a functionally related cohort of mRNAs linked to certain biological processes, including cell differentiation and cell fate determination. m⁶A is also enriched in other cohorts of mRNAs and can therefore affect their respective cellular processes and pathways. Future work will focus on understanding how the m⁶A pathway is regulated to achieve control of m⁶A-containing mRNAs.