RNA m6A modification and its function in diseases

Jiyu Tong,Hua-Bing Li,Richard A Flavell

doi:10.1007/s11684-018-0654-8

Jiyu Tong, Hua-Bing Li + Show 1 more

Open Access

https://doi.org/10.1007/s11684-018-0654-8

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Abstract

N6-methyladenosine (m6A) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism. m6A modification could be installed by m6A “writers” composed of core catalytic components (METTL3/METTL14/WTAP) and newly defined regulators and removed by m6A “erasers” (FTO and ALKBH5). The function of m6A is executed by m6A “readers” that bind to m6A directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or indirectly (HNRNPA2B1). In the past few years, advances in m6A modulators (“writers,” “erasers,” and “readers”) have remarkably renewed our understanding of the function and regulation of m6A in different cells under normal or disease conditions. However, the mechanism and the regulatory network of m6A are still largely unknown. Moreover, investigations of the m6A physiological roles in human diseases are limited. In this review, we summarize the recent advances in m6A research and highlight the functional relevance and importance of m6A modification in in vitro cell lines, in physiological contexts, and in cancers.

Highlights

Some RNA modifications, instead of being static, can be dynamically modified by enzymes with opposite modifying activities, indicating that these functional dynamic RNA modifications could be a new layer of gene regulation, termed “RNA epigenetics” [1]
Richard.flavell@yale.edu; Hua-Bing Li, huabing.li@shsmu.edu.cn surprisingly, the mapping approaches showed that m6A modification was highly enriched near stop codons and in 3′-UTRs in certain mRNAs, and the m6A levels varied in different cell contexts, indicating the critical roles of m6A in cells
METTL3 is a critical subunit of (N6adenosine)-methyltransferase [8]. It was highly conserved throughout eukaryotes, and METTL3 knockdown in different cells remarkably reduced m6A in mRNAs [5,9– 11]

Summary

Introduction

More than 100 chemical modifications have been identified in RNA, but most of their functions are still unknown. Richard.flavell@yale.edu; Hua-Bing Li, huabing.li@shsmu.edu.cn surprisingly, the mapping approaches showed that m6A modification was highly enriched near stop codons and in 3′-UTRs in certain mRNAs, and the m6A levels varied in different cell contexts, indicating the critical roles of m6A in cells.

Results

Conclusion