Role of N6-methyl-adenosine modification in mammalian embryonic development.

Chengshun Li,Dongxu Wang,Jindong Hao,Yan Gao,Ziping Jiang,Da Liu,Haobo Hu

doi:10.1590/1678-4685-gmb-2020-0253

Abstract

N6-methyl-adenosine (m6A) methylation is one of the most common and abundant modifications of RNA molecules in eukaryotes. Although various biological roles of m6A methylation have been elucidated, its role in embryonic development is still unclear. In this review, we focused on the function and expression patterns of m6A-related genes in mammalian embryonic development and the role of m6A modification in the embryonic epigenetic reprogramming process. The modification of m6A is regulated by the combined activities of methyltransferases, demethylases, and m6A-binding proteins. m6A-related genes act synergistically to form a dynamic, reversible m6A pattern, which exists in several physiological processes in various stages of embryonic development. The lack of one of these enzymes affects embryonic m6A levels, leading to abnormal embryonic development and even death. Moreover, m6A is a positive regulator of reprogramming to pluripotency and can affect embryo reprogramming by affecting activation of the maternal-to-zygotic transition. In conclusion, m6A is involved in the regulation of gene expression during embryonic development and the metabolic processes of RNA and plays an important role in the epigenetic modification of embryos.

Highlights

Modifications have been identified in different types of RNA, including mRNAs, tRNA, rRNA, and snoRNA, which are associated with various biological functions in mammals (Machnicka et al, 2013)
RNA methylation has an important role in mRNA modifications, such as N6-methyl-adenosine (m6A) modification, which is the most common methylation modification (Niu et al, 2013; Frye et al, 2018). m6A was found to be highly enriched in 3’ untranslated regions (UTR) or long internal exons, and 5’ UTRs (Dominissini et al, 2012; Meyer et al, 2012; Batista et al, 2014; Ke et al, 2015; Zhang and Hamada, 2018)
The knockout of methyltransferase-like 16 (METTL16) led to the dysregulation of gene expression, which in turn, resulted in the failure of further development of implanted embryos (Mendel et al, 2018). These findings suggested that methyltransferase-mediated m6A modification is necessary for embryonic development

Summary

Introduction

Modifications have been identified in different types of RNA, including mRNAs, tRNA, rRNA, and snoRNA, which are associated with various biological functions in mammals (Machnicka et al, 2013). It can be suggested that demethylases are involved in the dynamic process of m6A modification, which plays important roles in RNA export and metabolism, RNA processing factor assembly, and gene expression in mammalian embryonic development. The loss of YTHDF2 expression led to an imbalance in gene transcript regulation and affected oocyte development in mice (Ivanova et al, 2017). IGF2BPs as RNA-binding protein, play a potentially key role in embryonic development (Degrauwe et al, 2016).

Results

Conclusion