RNA结合蛋白调节对TGF-β的转录后反应,以协调小鼠内皮细胞的功能和介质细胞激活
Rhys Wardman1,2, Merve Keles1,2, Ihor Pachkiv1
1Department of Cardiovascular Physiology (R.W., M.K., I.P., S.H., S.G., J.H.), European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Germany.
Arteriosclerosis, thrombosis, and vascular biology
|August 31, 2023
概括
转化生长因子-β (TGF-β) 触发内皮细胞到介质细胞激活,这是与心血管疾病有关的过程. 这项研究揭示了RNA结合蛋白 hnRNP H1 和 Csde1 如何在转录后水平调节这种反应,维持内皮细胞功能.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 心血管研究研究心血管研究
背景情况:
- 内皮细胞 (ECs) 响应信号线索,例如转化生长因子-β (TGF-β).
- TGF-β诱导内皮细胞到介质酶激活 (EMA),这是一个涉及心血管疾病的过程.
- 在EC中,TGF-β对转录后调节的理解甚微.
研究的目的:
- 为了识别ECs中TGF-β调节的RNA结合蛋白 (RBPs) 的全球变化.
- 调查特异性RBPs,hnRNP H1和Csde1在TGF-β诱导的EMA中的作用.
- 阐明控制EC对TGF-β.反应的转录后机制.
主要方法:
- 捕获RNA相互作用组以识别TGF-β调节的RBP.
- RNA免疫沉和RNA测序以分析hnRNP H1和Csde1结合模式.
- 近距离结合试验以在现场可视化RBP-RNA相互作用.
主要成果:
- hnRNP H1和Csde1是ECs中TGF-β反应的关键转录后调节者.
- 失去了HnRNP H1或Csde1促进了EMA.
- TGF-β 增加了 hnRNP H1 的结合,并降低了 Csde1 结合目标 RNA 的结合,调节 EMA.
结论:
- 在TGF-β刺激期间,RBPs在ECs的转录后调节中发挥着关键作用.
- hnRNP H1 和 Csde1 维持 EC 功能并抵消 EMA.
- TGF-β修改RNA-蛋白相互作用以通过反和前控制微调EMA.
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