RNA结合蛋白SRSF3通过调节剪接和扩散来控制心表膜的形成
Irina-Elena Lupu1, Susann Bruche1, Anob M Chakrabarti2,3
1Institute of Developmental and Regenerative Medicine, British Heart Foundation Centre of Research Excellence, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX3 7TY, UK.
概括
在胚胎发育过程中,RNA结合蛋白SRSF3对于心上表皮形成至关重要. 它的删除会阻止心表细胞的增殖,影响心脏发育和再生.
科学领域:
- 心血管生物学 心血管生物学
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 副心脏在心脏发育和再生中起着至关重要的作用.
- 控制心上表皮形成的关键分子机制仍然不完全理解.
研究的目的:
- 研究RNA结合蛋白SRSF3在心上表皮形成和功能中的作用.
- 阐明SRSF3对心表发育的调节背后的分子机制.
主要方法:
- 采用了针对性Srsf3删除在前皮心的小鼠模型.
- 采用单细胞RNA测序来分析细胞对Srsf3枯竭的反应.
- 进行内源性irCLIP以映射SRSF3-RNA相互作用.
主要成果:
- 在小鼠前皮心脏中Srsf3的缺失导致了增殖停止和表皮心形成障碍.
- 由于Srsf3的枯竭,导致表心增殖和表心衍生细胞 (EPDC) 的形成减少.
- SRSF3与细胞循环调节器Ccnd1和Map4k4结合,影响了拼接和非拼接功能.
结论:
- SRSF3对于控制心上表膜增殖和确保正确的心上表膜形成至关重要.
- 通过依赖拼接和独立的机制,SRSF3调节心脏发育.
- 马赛克重组可以显著混胚胎表型,强调SRSF3的调节作用的重要性.
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