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

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.

Y‐box binding protein 1 influences zygotic genome activation by regulating N6‐methyladenosine in porcine embryos

“…Previous studies reported that downregulation of m6A writer METTL3 and reader IGF2BP1 and YTHDF2 impaired early embryo development (Deng et al, 2020; Hao et al, 2020; Ivanova et al, 2017; Xia et al, 2018). Moreover, knockout of METTL3 or knockdown of IGF2BP1 reduced the m6A modification level (Chang et al, 2022; Hao et al, 2020). In addition, YBX1 interacts with IGF2BPs and stabilizes m6A‐tagged RNA (Feng et al, 2021) and IGF2BP1 is highly correlated with YBX1 (Deng et al, 2022), suggesting that YBX1 may be related to m6A.…”

Connecting the Dots: N6‐Methyladenosine (m6A) Modification in Spermatogenesis

“…[49] Recent studies have shown that YTHDF2 is required for the development of spermatogonia. [20][21][22][23] The inhibition of the G2 phase in GC-1 cells was caused by Ythdf2 depletion. Furthermore, YTHDF2 modulated cell-matrix adhesion mainly by regulating matrix metallopeptidase (MMPs) and extracellular matrix (ECMs) expression, and matrix metallopeptidase 13 (Mmp13) is an important target for YTHDF2 to regulate the phenotype.…”

“…Recent studies have summarized the role of m 6 A in spermatogenesis. [19][20][21][22][23] However, the mechanism by which m 6 A catalase enzymes contribute to specific germ cell stages remains unknown. Single-cell sequencing (scRNA-seq) techniques allow us to visualize the expression profile of m 6 A catalase enzymes in different germ cells.…”

m6A ‘writer’ KIAA1429 regulates the proliferation and migration of endothelial cells in atherosclerosis

“…N 6 -methyladenosine (m 6 A) acts as the most abundant posttranscriptional modification for mRNAs, which partially determines the fate of RNA, including RNA stabilization, splicing, and nuclear export [ 9 , 10 ]. m 6 A methylations have been shown to regulate series of inflammatory processes, including the inflammatory vascular disorder of endothelial cells in AS [ 11 ].…”