Chemical Modifications in the Life of an mRNA Transcript

Investigations over the past eight years of chemical modifications on messenger RNA (mRNA) have revealed a new level of posttranscriptional gene regulation in eukaryotes. Rapid progress in our understanding of these modifications, particularly, N⁶-methyladenosine (m⁶A), has revealed their roles throughout the life cycle of an mRNA transcript. m⁶A methylation provides a rapid mechanism for coordinated transcriptome processing and turnover that is important in embryonic development and cell differentiation. In response to cellular signals, m⁶A can also regulate the translation of specific pools of transcripts. These mechanisms can be hijacked in human diseases, including numerous cancers and viral infection. Beyond m⁶A, many other mRNA modifications have been mapped in the transcriptome, but much less is known about their biological functions. As methods continue to be developed, we will be able to study these modifications both more broadly and in greater depth, which will likely reveal a wealth of new RNA biology.