Structural Insights into N6-methyladenosine (m6A) Modification in the Transcriptome

Ping Yin,Jinbo Huang

doi:10.1016/j.gpb.2018.03.001

Abstract

More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine (m6A), have been detected in mRNA, opening the window into the realm of epitranscriptomics. The m6A modification is the most abundant modification in mRNA and non-coding RNA (ncRNA). At the molecular level, m6A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA (miRNA) maturation, playing essential roles in a range of cellular processes. The m6A modification is regulated by three classes of proteins generally referred to as the “writer” (adenosine methyltransferase), “eraser” (m6A demethylating enzyme), and “reader” (m6A-binding protein). The m6A modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology (YTH) family proteins, selectively bind to RNA and affect its fate in an m6A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m6A modification, and provide our insights into the m6A-mediated gene regulation.

Highlights

RNA plays a significant role in the life cycle
Tremendous progress has been achieved in exploring the molecular mechanisms underlying reversible modification and m6A recognition both in vivo and in vitro in recent years, some questions and debates remain [56,88,124,125]
How the consensus mRNA sequence is recognized by the writer complex is poorly understood

Summary

Introduction

RNA plays a significant role in the life cycle. Since the 1950s, more than 100 types of chemical modifications have been described in RNA, in rRNA and tRNA [1]. AdoMet, S-adenosylmethionine; ALKBH5, AlkB homolog 5; FTO, fat mass and obesity-associated protein; HAKAI, E3 ubiquitin-protein ligase Hakai; KIAA1429, vir-like m6A methyltransferase associated protein; METTL3, methyltransferase-like 3; MTase, methyltransferase; RBM15/15B, RNA binding motif protein 15/15B; WTAP, Wilms’ tumor 1associating protein; YTH, YT521-B homology; ZC3H13, zinc finger CCCH domain-containing protein 13; ZnF, zinc finger domain.

Results

Conclusion