通过DHX36介导的G四复合体解对于卵细胞和小鼠早期胚胎发育至关重要
Yu-Xuan Jiao1, Guo-Wei Bu2, Yun-Wen Wu1
1MOE Key Laboratory for Biosystems Homeostasis, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Science bulletin
|March 1, 2025
概括
在小鼠中,DHX36缺乏会通过破坏rRNA稳态和卵细胞中的染色质结构而导致不孕. 这导致激素反应,排卵和胚胎发育受损,这是由于G-四重复的增加造成的.
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 遗传学 是一个
背景情况:
- DHX36 (DEAH-box helicase 36) 对于通过G-四重复合体 (G4s) 的基因调节至关重要.
- 它在卵细胞发育和女性生育方面的特定作用仍然在很大程度上未被探索.
研究的目的:
- 研究DHX36在小鼠卵细胞发育和女性生育中的功能.
- 阐明DHX36在rRNA恒温和染色体调节中的作用背后的分子机制.
主要方法:
- 生产缺少DHX36.6的卵细胞特异性条件淘汰 (CKO) 鼠标.
- 对卵细胞形态,染色质,转录组和介质进展的分析.
- 评估rRNA转录,rRNA前处理和翻译.
- G4检测和DHX36定位研究.
- 在体外结合试验和DHX36过度表达实验.
主要成果:
- CKO小鼠表现出不孕症,荷尔蒙反应和排卵受损.
- CKO卵细胞显示出异常的核细胞,染色素和抑制的半分裂.
- 缺乏导致rRNA转录减少,rRNA前处理和翻译受损.
- 在CKO卵细胞中观察到G4形成的增加,特别是来自rDNA和pre-rRNA的增加.
- DHX36直接与前rRNA结合,而它的缺失会破坏rRNA稳态和染色质结构.
结论:
- 在小鼠中,DHX36对于维持雌性生育能力至关重要.
- DHX36通过G4解来调节卵细胞中的rRNA稳态和染色质配置.
- 破坏DHX36功能会导致卵细胞发育缺陷和不孕症.
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