生殖基础研究 RNA N6-甲基腺苷(m6A)修饰相关酶在哺乳动物精子发生中的研究进展

doi:10.16352/j.issn.1001-6325.2023.04.0524

摘要/Abstract

摘要： N6-甲基腺苷(m6A)核酸修饰是近10年来研究较多的一类表观修饰,RNA通过经典m6A修饰蛋白“Writers”(METTL3/14/WTAP等)、m6A去修饰蛋白“Erasers”(FTO和ALKBH5)和m6A识别蛋白“Readers”(YTHDC1/2、YTHDF1/2/3等)组成的协同调节体系进行转录后核酸m6A修饰、去修饰和识别结合,进而调控转录本下游命运。精子发生是雄性哺乳动物性成熟和维持生育能力的重要过程,涉及生精上皮支持细胞、间质细胞和精原细胞等增殖分化和维持生精微环境过程。多项研究表明m6A调节体系参与哺乳动物精子发生进程,异常的m6A修饰水平和m6A调节体系失衡均会导致睾丸发育异常、精子发生异常和雄性不育。本文综述了精子发生过程中m6A修饰相关酶的作用,深入分析m6A差异修饰转录本之于正常精子发生的作用,对认知哺乳动物精子发生和解析临床生精障碍的分子机制具有重要意义。

关键词: m6A修饰, 精子发生, 支持细胞, 间质细胞, 生精细胞

Abstract: N-6-methyladenosine(m6A) has been well-known to be a type of RNA epigenetic modification over the past decade. The m6A modification enzymes include “Writers” (METTL3/14/WTAP, etc.),“Erasers” (FTO and ALKBH5) and “Readers” (YTHDC1/2,YTHDF1/2/3, etc.), which mediate RNA methylation, demethylation, and recognition binding via a synergistic regulatory system, thereby regulating the fate of RNA after transcription. Spermatogenesis is an essential process of sexual maturation and maintenance of fertility in male mammals, involving the proliferation, and differentiation of Sertoli cells, Leydig cells and spermatogonia, and maintenance of spermatogenic microenvironment. More recently, there are some researches showed that the m6A regulatory system was involved in mammalian spermatogenesis. Abnormal m6A modification and imbalances in the m6A regulatory system can lead to abnormal testicular development, abnormal spermatogenesis and male infertility. This review summarizes the function of m6A modification enzymes in spermatogenesis, and further analyzes the role of m6A differentially modified transcripts in normal spermatogenesis, which has a great significance for understanding mammalian spermatogenesis and decoding the molecular mechanism of clinical spermatogenesis disorders.

Key words: m6A modification, spermatogenesis, Sertoli cell, Leydig cell, spermatogenic cell

中图分类号:

张强, 宿文辉. 生殖基础研究 RNA N6-甲基腺苷(m6A)修饰相关酶在哺乳动物精子发生中的研究进展[J]. 基础医学与临床, 2023, 43(4): 524-531.

ZHANG Qiang, SU Wenhui. Advances in research on RNA N-6-methyladenosine(m6A) modification related enzymes in mammalian spermatogenesis[J]. Basic & Clinical Medicine, 2023, 43(4): 524-531.

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