删除RNA G-四重复的过程促进了在半分裂恢复后的翻译切换
Qiong-Wen Lu1,2, Shao-Yuan Liu1, Xiu-Quan Liao1
1GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou 510006, China.
Nucleic acids research
|April 30, 2025
概括
鼠标卵细胞中的RNA G-四重复 (rG4s) 在半分裂前保持低翻译. 通过DHX36去除它们对于母亲到卵巢的过渡和成功的发育至关重要.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 生殖生物学 生殖生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 卵细胞成熟依赖于转录后mRNA调节的发育潜力.
- 以前的研究集中在RNA结合蛋白 (RBPs) 上,忽视了RNA结构的作用.
- RNA G-四复合体 (rG4s) 是影响RNA代谢的RNA二级结构.
研究的目的:
- 研究rG4s在小鼠卵细胞中的分布,动态和调控作用.
- 了解rG4s如何影响卵细胞成熟期间的mRNA翻译.
- 为了确定在变化过程中参与rG4调节的因素.
主要方法:
- 开发了G4-LACE-seq,这是一种低输入技术,用于在小鼠卵细胞中检测rG4.
- 使用了选择性rG4小分子接体BYBX来稳定rG4s.
- 采用蛋白质组分析,RBP免疫沉和翻译报告员测试.
- 研究了DEAH/RHA家族酶-36 (DHX36) 的作用.
主要成果:
- rG4s在母体转录中广泛存在,在未翻译的区域中被丰富,并在成熟过程中被删除.
- 通过BYBX治疗稳定了rG4s,损害了线组装和细胞周期进展.
- rG4积累削弱了RBP与mRNA的结合,特别是那些用于翻译启动的mRNA.
- rG4s对母体mRNA的翻译效率产生了负面影响.
- DHX36过度表达部分挽救了BYBX诱导的发育缺陷.
结论:
- rG4s对于维持低转化体在卵细胞中在半球变异恢复之前至关重要.
- 通过DHX36介导的rG4去除促进了对母体转化为胚胎的转换所必需的转化开关.
- 这项研究阐明了rG4s及其对卵细胞发育潜力的调节的关键作用.
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