通过与PIWIL1的相互作用来调节男性特异性保存的LncRNA TSCL1调节的目标mRNA翻译
Shuai Lu1,2,3, Yang Li1,2, Chenmeijie Li1,2
1State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Cell death and differentiation
|September 20, 2025
概括
丸特异性保存的lncRNA 1 (Tscl1) 对于男性生育能力至关重要. 它通过增强关键代谢基因的翻译来调节精子的发育,其破坏会导致不孕症,并与非阻塞性精子缺血有关.
科学领域:
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 长非编码RNA (lncRNAs) 在哺乳动物生理学中至关重要,但它们在精子发育中的作用尚不清楚.
- 随卵性精子相关的 lncRNAs (cHS-LncRNAs) 是保存的,丸特异的,并且在精子中丰富.
研究的目的:
- 研究cHS-LncRNAs在精子生成中的功能.
- 为了确定涉及男性生育能力的特定 lncRNA.
主要方法:
- 鉴定和表征保存的单双精子相关 lncRNAs (cHS-LncRNAs).
- 产生和分析Tscl1-null小鼠以评估生育能力和精子参数.
- 生物化学测试以确定 Tscl1 作用的分子机制,包括蛋白质结合和复合物形成.
- 在患有非阻塞性精子缺血症 (NOA) 的患者中分析TSCL1基因变异.
主要成果:
- Tscl1是圆形精子体中表达最高的cHS-lncRNA.
- 在小鼠中,Tscl1 缺乏导致精子运动率降低,线粒体膜失调,脂肪酸代谢发生变化和不孕.
- Tscl1与PIWIL1和HuR相互作用,通过PIWIL1/eIF3f/HuR/eIF4G3复合体促进与脂肪酸代谢相关的mRNA的翻译.
- 影响PIWIL1结合的TSCL1变异在患有NOA的男性中更常见.
结论:
- Tscl1在精子生成过程中调节翻译起着至关重要的作用,确保精子的正常发育和功能.
- Tscl1对男性生育能力至关重要,其功能障碍与人类男性不孕症有关,特别是NOA.
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