特定于PIWI的插入模块有助于加载更长的piRNA,以进行对男性生育能力至关重要的转化激活
Xin Wang1,2, Di-Hang Lin2, Yue Yan2
1Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
Science China. Life sciences
|June 19, 2023
概括
PIWI蛋白质使用PIWI相互作用RNAs (piRNAs) 进行功能. 在PIWI蛋白中的一个独特的PIWI-Ins模块决定了piRNA的长度,这对男性生育能力和精子发育至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生殖生物学 生殖生物学
背景情况:
- PIWI-clade蛋白质对于小RNA引导的基因沉默至关重要,利用PIWI相互作用RNA (piRNAs) 通常长达24-33个核酸.
- 通过PIWI蛋白质结合不同大小的piRNA的机制以及piRNA长度的功能意义仍然不太清楚.
研究的目的:
- 研究PIWI蛋白质中独特的PIWI-Ins模块在确定piRNA长度中的作用.
- 阐明改变piRNA长度对PIWI/piRNA复合体功能,精子生成和男性生育能力的功能后果.
主要方法:
- 在小鼠中利用基因操纵,包括在Miwi中删除PIWI-Ins模块,并生成具有特定人类PIWI-Ins突变的Miwi敲入小鼠.
- 采用生物化学测试来分析PIWI/piRNA复合体形成和RNA结合性质.
- 评估了基因修改对piRNA长度选择,目标mRNA互补性,超复杂组合和男性生育能力的影响.
主要成果:
- 在Miwi中删除PIWI-Ins模块导致加载较短的piRNA,并导致小鼠的精子生成失败.
- 长的piRNA被证明可以通过增加对目标mRNA的互补性来增强PIWI/piRNA向能力,并通过MIWI/eIF3f/HuR超复合体促进转化激活.
- 在不育男性中发现的一种人类PIWIL1 (HIWI) 突变 (c.1108C>T,p.R370W) 通过破坏PIWI-Ins介导的更长piRNAs的选择,损害了男性生育能力.
结论:
- PIWI-Ins模块对于确保PIWI蛋白质将功能适当长度的piRNA纳入PIWI蛋白质至关重要.
- 通过PIWI-Ins介导的较长piRNA的选择对于强大的PIWI/piRNA向,精子发育和维持男性生育能力至关重要.
- 在PIWI-Ins模块中的遗传变化可以直接损害男性生殖健康.
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