Roles of N6-Methyladenosine (m6A) in Stem Cell Fate Decisions and Early Embryonic Development in Mammals

Meng Zhang,Xiangpeng Dai,Ziyi Li,Yanhui Zhai,Sheng Zhang

doi:10.3389/fcell.2020.00782

Abstract

N6-methyladenosine (m6A) is one of the most abundant internal mRNA modifications, and it affects multiple biological processes related to eukaryotic mRNA. The majority of m6A sites are located in stop codons and 3′UTR regions of mRNAs. m6A regulates RNA metabolism, including alternative splicing (AS), alternative polyadenylation (APA), mRNA export, decay, stabilization, and translation. The m6A metabolic pathway is regulated by a series of m6A writers, erasers and readers. Recent studies indicate that m6A is essential for the regulation of gene expression, tumor formation, stem cell fate, gametogenesis, and animal development. In this systematic review, we summarized the recent advances in newly identified m6A effectors and the effects of m6A on RNA metabolism. Subsequently, we reviewed the functional roles of RNA m6A modification in diverse cellular bioprocesses, such as stem cell fate decisions, cell reprogramming and early embryonic development, and we discussed the potential of m6A modification to be applied to regenerative medicine, disease treatment, organ transplantation, and animal reproduction.

Highlights

Since the discovery of the first structurally modified nucleoside, pseudouridine, in the 1950s (Cohn and Volkin, 1951), more than 150 kinds of chemical modifications have been found on cellular RNA (Boccaletto et al, 2018)
We summarized the latest progress regarding the molecular basis of m6A effectors and discussed the functional roles of m6A modification in the regulation of RNA metabolism
In HeLa cells, PAR-CLIP data analysis suggested that methyltransferase-like 3 (METTL3) and Wilms tumor 1-associating protein (WTAP) affected mRNA alternative splicing (AS) and the expression of genes related to transcription and RNA processing (Ping et al, 2014)

Summary

Introduction

Since the discovery of the first structurally modified nucleoside, pseudouridine, in the 1950s (Cohn and Volkin, 1951), more than 150 kinds of chemical modifications have been found on cellular RNA (Boccaletto et al, 2018). We focused on the molecular regulation mechanism of m6A modification in stem cell fate decisions and early embryonic development. In HeLa cells, PAR-CLIP data analysis suggested that METTL3 and WTAP affected mRNA AS and the expression of genes related to transcription and RNA processing (Ping et al, 2014).

Results

Conclusion