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

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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.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81971444 to S.Y.), the Science Technology and Innovation Commission of Shenzhen Municipality (JCYJ20170244 to S.Y.), and the Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine, Ferring Pharmaceuticals and Chinese Academy of Sciences (FIRMSCOV02 to S.Y.).

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  1. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yiqian Gui & Shuiqiao Yuan

  2. Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518057, China

    Shuiqiao Yuan

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  1. Yiqian Gui
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YG reviewed the literature and wrote the manuscript, SY conceived and revised the manuscript.

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Gui, Y., Yuan, S. Epigenetic regulations in mammalian spermatogenesis: RNA-m6A modification and beyond. Cell. Mol. Life Sci. 78, 4893–4905 (2021). https://doi.org/10.1007/s00018-021-03823-9

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