PDGFRα信号调节Srsf3转录结合以影响PI3K信号和内体细胞贩运
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, CO, USA.
bioRxiv : the preprint server for biology
|April 15, 2024
概括
血小板衍生生长因子受体α (PDGFRα) 信号调节RNA剪接因子Srsf3,影响面发育. 这项研究揭示了PDGFRα如何控制Srsf3来管理正确面部形成的基因表达.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 血小板衍生生增长因子受体α (PDGFRα) 信号传递对面发育至关重要,突变与唇裂相关.
- 酸氨基3-激酶 (PI3K) /Akt通路是骨发育中的PDGFRα信号传递的关键作用因子.
- 富含氨酸/氨酸的剪接因子3 (Srsf3) 被PDGFRα信号的下游Akt酸化,转移到核中并影响替代RNA剪接 (AS).
研究的目的:
- 阐明Srsf3活性由PDGFRα信号调节的分子机制.
- 了解Srsf3如何控制面发育所必需的转录的AS.
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.
- 功能验证研究.
主要成果:
- 通过PDGF-AA刺激改变了Srsf3与RNA的结合,使其更喜欢外因子而不是正规动机.
- Srsf3活动促进了具有更高GC含量和更短内子的外子包含.
- 受影响的转录通常编码PI3K信号传递和内体体贩运的调节者.
- 在早期内分泌体中,Srsf3活性保留了PDGFRα,增强了PI3K/Akt信号传递.
结论:
- 增长因子介导的Srsf3酸化是调节面发育中的基因表达的一个关键机制.
- 这条通路控制替代拼接,以确保适当的细胞增殖,生存和受体贩运.
- 这些发现揭示了生长因子信号,RNA结合蛋白和发育过程之间的新联系.
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