PDGFRα信号调节Srsf3转录结合以影响PI3K信号和内体体贩运
Thomas E Forman1,2, Marcin P Sajek3,4,5, Eric D Larson6,7
1Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, United States.
eLife
|December 4, 2024
概括
血小板衍生生长因子受体α (PDGFRα) 信号通过酸化RNA结合蛋白Srsf3来调节面发育,影响替代拼接和细胞信号通路.
科学领域:
- 分子生物学分子生物学
- 发育生物学是发展生物学.
- 遗传学 遗传学 是一个
背景情况:
- 血小板衍生生长因子受体α (PDGFRα) 信号传递对面发育至关重要.
- 酸氨基3-激酶 (PI3K) /Akt通路是骨发育中的PDGFRα信号传递的关键媒介.
- 富含氨酸/氨酸的剪接因子3 (Srsf3) 被PDGFRα信号的下游Akt酸化,转移到核中.
研究的目的:
- 研究Srsf3通过PDGFRα信号的下游调节面发育的分子机制.
- 确定PDGF-AA刺激如何影响Srsf3与RNA结合及其对替代拼接的影响.
- 阐明Srsf3在PDGFRα信号传递中的作用及其对PI3K/Akt通路的下游影响.
主要方法:
- 在小鼠胚胎 palatal mesenchyme (MEPM) 细胞中增强紫外线交叉连接和免疫沉 (eCLIP).
- RNA测序 (RNA-seq) 用于分析替代拼接变化.
- 分析Srsf3对外子和RNA动机的结合偏好.
主要成果:
- 刺激PDGF-AA促进Srsf3与外子的结合,并减少与CA丰富基因的结合.
- Srsf3活动驱动了具有较短内子的GC丰富异构体的优先包含.
- 在早期内体中,Srsf3促进PDGFRα保留,增强PI3K/Akt信号传递.
结论:
- 通过生长因子介导的Srsf3酸化是哺乳动物面发育的关键调节机制.
- Srsf3作为一个关键节点,将PDGFRα信号连接到替代RNA拼接.
- 这种途径的失调可能会导致面异常.
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