Chemical Modifications to RNA: A New Layer of Gene Expression Regulation

The first chemical modification to RNA was discovered nearly 60 years ago; to date, more than 100 chemically distinct modifications have been identified in cellular RNA. With the recent development of novel chemical and/or biochemical methods, dynamic modifications to RNA have been identified in the transcriptome, including N-6-methyladenosine (m(6)A), inosine (I), 5-methylcytosine (m(5)C), pseudouridine (Psi), 5-hydroxymethylcytosine (hm(5)C), and N-1-methyladenosine (m(1)A). Collectively, the multitude of RNA modifications are termed epitranscriptome, leading to the emerging field of epitranscriptomics. In this review, we primarily focus on recently reported chemical modifications to mRNA; we discuss their chemical properties, biological functions, and mechanisms with an emphasis on their high-throughput detection methods. We also envision that future tools, particularly novel chemical biology methods, could further facilitate and enable studies in the field of epitranscriptomics.