Voyages to map unexplored parts of the epitranscriptomic world

Abstract

Nascent transcripts are subject to extensive processing, such as 5ʹ capping, splicing, 3ʹ polyadenylation, RNA editing, and RNA modifications. The transcriptome plasticity conferred by these posttranscriptional regulations can alter gene expression, which is a major driver of proteomic diversity. Similar to epigenetic modifications on DNA and histone proteins, RNA is also subject to various chemical modifications, called epitranscriptomic modifications. Since the first chemical modification of RNA was identified approximately 60 years ago, more than 170 RNA modifications have been identified, including N6-methyladenosine (m6A), pseudouridine (Ψ), 2ʹ-O-methylation, (Nm), 5-methylcytidine (m5C), and 8-oxoguanine (o8G). Different RNA species, such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), messenger RNAs (mRNAs), and noncoding RNAs (ncRNAs), are frequently posttranscriptionally modified. In particular, studies in the past decade have suggested that these modifications influence almost all aspects of RNA metabolism, including stability, splicing, localization, RNA–protein interaction, and translation1. Indeed, these RNA modifications exhibit essential functions in many biological contexts, including normal development, adult tissue homeostasis, and cancer2,3.