微RNA和RNA结合蛋白的协调后转录调节对于早期胚胎细胞命运决定至关重要
Carolyn Sangokoya1,2, Robert Blelloch1,2,3
1The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
RNA结合蛋白 (RBPs) 和微RNAs协调以控制Profilin 2 (Pfn2) mRNA. 这种调节对于胚胎干细胞分化成生殖层至关重要.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 干细胞生物学 干细胞生物学
背景情况:
- 通过RNA结合蛋白 (RBPs) 和微RNA进行转录后调节对于mRNA稳定性和翻译至关重要.
- 在发育过程中调节细胞命运的RBPs和microRNAs的协调作用仍然在很大程度上未被探索.
研究的目的:
- 为了研究胚胎干细胞 (ESC) 分化过程中RBPs和microRNAs对单个转录物Profilin 2 (Pfn2) 的协调控制.
- 阐明这种调节在形成初级生殖层血统中的重要作用.
主要方法:
- 对铁调节蛋白 (IRP) 和ESC丰富的微RNA的结合位点的Pfn2 3'未翻译区域的分析.
- 基因操纵涉及删除microRNA结合部位和铁反应元素 (IRE).
- 在ESC差异化过程中评估PFN2表达水平和关键信号通路 (FGF和Wnt).
主要成果:
- 删除Pfn2上的microRNA结合部位导致PFN2水平增加,并在多能过渡期间减少FGF信号传递.
- 删除对铁反应元素 (IRE) 导致PFN2水平降低,Wnt信号缺陷,核β-catenin减少,并阻断间皮系谱的形成.
- Pfn2转录由协调的microRNA-IRE轴调节,这对于ESC差异化中的关键信号传导事件至关重要.
结论:
- 通过RBPs和microRNAs对Pfn2转录的协调调节对于胚胎干细胞分化成生殖层至关重要.
- 在Pfn2上的microRNA-IRE轴控制关键信号通路,包括FGF和Wnt,从而在早期发育过程中决定细胞命运.
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