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Review
. 2021 Jun;78(11):4893-4905.
doi: 10.1007/s00018-021-03823-9. Epub 2021 Apr 9.

Epigenetic regulations in mammalian spermatogenesis: RNA-m6A modification and beyond

Yiqian Gui  1 , Shuiqiao Yuan  2   3
Affiliations
Review

Epigenetic regulations in mammalian spermatogenesis: RNA-m6A modification and beyond

Yiqian Gui et al. Cell Mol Life Sci. 2021 Jun.

Abstract

Emerging evidence shows that m6A, one of the most abundant RNA modifications in mammals, is involved in the entire process of spermatogenesis, including mitosis, meiosis, and spermiogenesis. "Writers" catalyze m6A formation on stage-specific transcripts during male germline development, while "erasers" remove m6A modification to maintain a balance between methylation and demethylation. The different functions of RNA-m6A transcripts depend on their recognition by "readers". m6A modification mediates RNA metabolism, including mRNA splicing, translation, and degradation, as well as the maturity and biosynthesis of non-coding RNAs. Sperm RNA profiles are easily affected by environmental exposure and can even be inherited for several generations, similar to epigenetic inheritance. Here, we review and summarize the critical role of m6A in different developmental stages of male germ cells, to understand of the mechanisms and epigenetic regulation of m6A modifications. In addition, we also outline and discuss the important role of non-coding RNAs in spermatogenesis and RNA modifications in epigenetic inheritance.

Keywords: Epigenetic inheritance; RNA modification; Sperm RNA; Spermatogenesis; m6A.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Fig. 1
Fig. 1
A schematic diagram of mouse spermatogenesis
Fig. 2
Fig. 2
The function of m6A-associated proteins in spermatogenesis. “Writers” catalyze m6A formation on stage-specific transcripts during male germline development while “erasers” remove m6A modification to maintain a balance between methylation and demethylation. The different functions of m6A transcripts (splicing, translation, and degradation) depend on their recognition by “readers.” Abnormal expression of m6A-associated proteins in different developmental stages results in male infertility
Fig. 3
Fig. 3
A schematic diagram of epigenetic response to environmental insults. Epigenetic alterations (DNA methylation, histone modification, m6A modification, and non-coding RNAs) induced by an environmental exposure can substantially affect the sperm function and have an inter-/transgenerational inheritance effect
See this image and copyright information in PMC

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