Genetic Regulation of N6-Methyladenosine-RNA in Mammalian Gametogenesis and Embryonic Development.

Yuguang Chang,Jing Wang,Zafir Muhammad,Zhikun Cao,Tingting Zhou,Massimo De Felici,Yanqin Feng,Zijun Zhang,Mingliang Yi,Zihui Yan,Hongguo Cao,Wei Shen,Wei Ge

doi:10.3389/fcell.2022.819044

Abstract

Emerging evidence shows that m6A is the most abundant modification in eukaryotic RNA molecules. It has only recently been found that this epigenetic modification plays an important role in many physiological and pathological processes, such as cell fate commitment, immune response, obesity, tumorigenesis, and relevant for the present review, gametogenesis. Notably the RNA metabolism process mediated by m6A is controlled and regulated by a series of proteins termed writers, readers and erasers that are highly expressed in germ cells and somatic cells of gonads. Here, we review and discuss the expression and the functional emerging roles of m6A in gametogenesis and early embryogenesis of mammals. Besides updated references about such new topics, readers might find in the present work inspiration and clues to elucidate epigenetic molecular mechanisms of reproductive dysfunction and perspectives for future research.

Highlights

The emerging field of RNA modification is stimulating large-scale research
Among the key genes involved in m6A modification, METTL3, METTL14 and ALKBH5 were highly expressed in mouse oocytes and played important biological functions (Sui et al, 2020)
In fully grown mouse germinal vesicles (GV) oocytes, METTL3 knockout seriously inhibits maturation and leads to abnormal maternal-to-zygotic transition (MZT) in the embryo, which may be caused by lowering mRNA translation efficiency of genes such as Cltc, Pcnt, Spdl-1 and Msy2 and/or interfering with their transcript degradation (Sui et al, 2020)

Summary

Introduction

The emerging field of RNA modification is stimulating large-scale research. Compared with DNA methylation, RNA methylation is more diverse and widespread in various advanced organisms and widely affects various biological processes by regulating post-transcriptional gene expression. In the testis of infertile “Ketu” mutant mice with missense YTHDC2 mutation, germ cells experienced a failed meiosis attempt and tried to start the expression of landmark meiotic proteins and DNA recombination, but still could not completely shut down the mitotic process of spermatogonia, resulting in premature entry into an abnormal metaphase like state, and enter the outcome of apoptosis (Jain et al, 2018).

Results

Conclusion