Journal Article

The epitranscriptome beyond m6A

Wiener, David, Schwartz Schraga

2021

Overview

Following its transcription, RNA can be modified by >170 chemically distinct types of modifications — the epitranscriptome. In recent years, there have been substantial efforts to uncover and characterize the modifications present on mRNA, motivated by the potential of such modifications to regulate mRNA fate and by discoveries and advances in our understanding of N6-methyladenosine (m6A). Here, we review our knowledge regarding the detection, distribution, abundance, biogenesis, functions and possible mechanisms of action of six of these modifications — pseudouridine (Ψ), 5-methylcytidine (m5C), N1-methyladenosine (m1A), N4-acetylcytidine (ac4C), ribose methylations (Nm) and N7-methylguanosine (m7G). We discuss the technical and analytical aspects that have led to inconsistent conclusions and controversies regarding the abundance and distribution of some of these modifications. We further highlight shared commonalities and important ways in which these modifications differ with respect to m6A, based on which we speculate on their origin and their ability to acquire functions over evolutionary timescales.This Perspective reviews efforts to map six different RNA modifications — pseudouridine (Ψ), 5-methylcytidine (m5C), N1-methyladenosine (m1A), N4-acetylcytidine (ac4C), ribose methylations (Nm) and N7-methylguanosine (m7G) — and how they differ from N6-methyladenosine (m6A). The authors discuss the technical and analytical challenges of characterizing the epitranscriptome and provide their own conclusions on the abundance and distribution of these modifications.

• Publisher: Nature Publishing Group
• Subject: Abundance / Biosynthesis / Chromatography / Epigenetics / Mass spectrometry / N6-methyladenosine / Ribose / Scientific imaging / Transcription