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通过METTL16介导的替代拼接和翻译控制对于小鼠精子生成至关重要

Qian Ma¹, Yiqian Gui², Xixiang Ma³

¹Department of Urology, Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China.

|July 19, 2024

概括

甲基转移酶类蛋白16 (METTL16) 对于男性生育至关重要,在精子发生过程中,在线粒分裂转变为分裂转变过程中调节基因表达. 它的甲基转移酶活性确保了胚胎细胞发育的适当拼接和翻译.

科学领域:

生殖生物学生殖生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
分子遗传学分子遗传学

背景情况:

精子生成涉及从线粒分裂转变为半分裂的关键转换,需要精确的基因表达调节.
在这种过渡期间控制介质转录和后转录过程的机制尚未完全理解.

研究的目的:

调查甲基转移酶类蛋白16 (METTL16) 在精子生成过程中线粒分裂转变为半分裂转变中的作用.
阐明METTL16调节男性生殖细胞基因表达的分子机制.

主要方法:

在雄性小鼠中,Mettl16的生殖线条件淘汰.
与拼接因子的相互作用研究.
核糖体造型和m6A测序. 核糖体造型和m6A测序. 核糖体造型和m6A测序.
在体内和体外功能测定.

主要成果:

梅特尔16淘汰赛会影响精子的分化和半分裂的启动.
METTL16调节了与半变异相关的基因 (例如,Stag3) 的替代拼接和半变异基因的翻译效率.
移除METTL16会改变m6A修饰的转录水平,影响基因表达.
METTL16的甲基转移酶活性对于精子生成至关重要.

结论:

METTL16充当m6A写字体,通过调节替代拼接和翻译效率来控制生殖细胞的命运.
这项研究提供了一个分子模型,用于METTL16的功能,在线粒分裂到变的开关.
这些发现对了解与介质性疾病相关的男性不孕症有意义.

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