受到疾病的控制:酸化调节了SRSF1域的可用性,用于spliceosome组装
Talia Fargason1, Erin Powell1, Naiduwadura Ivon Upekala De Silva1
1Department of Chemistry, College of Arts and Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Protein science : a publication of the Protein Society
|February 19, 2025
概括
酸化氨酸/氨酸丰富的剪接因子1 (SRSF1) 改变了它与蛋白质和RNA的相互作用. 这一修改影响了SRSF1.
科学领域:
- 分子生物学分子生物学
- 生物化学 生化学
- 在RNA生物学,RNA生物学.
背景情况:
- 富含氨酸/氨酸的拼接因子1 (SRSF1) 对于mRNA处理至关重要,包括转录,拼接和核出口.
- 功能障碍的SRSF1与各种疾病有关,包括癌症和发育障碍.
- SRSF1的功能取决于与蛋白质和RNA的相互作用,由其氨酸/氨酸丰富的尾巴 (RS) 的酸化调节.
研究的目的:
- 研究SRSF1RS尾巴的酸化如何影响其蛋白质和RNA相互作用.
- 为了阐明酸化对SRSF1相分离特性的影响.
- 了解SRSF1酸化在早期结合体组装中的作用.
主要方法:
- 核磁共振 (NMR) 偏磁放松增强 (rE) 核磁共振 (NMR) 偏磁放松增强 (rE)
- 核磁共振的化学转移扰动 (CSP)
- 对蛋白质-RNA相互作用和相分离的分析.
主要成果:
- 非化SRSF1的RS尾巴与RRM1蛋白结合部位相互作用.
- 对RS的酸化减少了与RRM1蛋白结合部位的相互作用,但增加了与RRM1RNA结合部位的相互作用.
- 酸化削弱了SRSF1的RNA结合,并通过减少阿尔金因在分子间相互作用中的作用来改变其相位分离.
结论:
- 酸化动态调节SRSF1的分子内相互作用,影响其蛋白质和RNA结合亲缘关系.
- 由于酸化而改变的SRSF1相互作用会影响其相位分离行为.
- 这些发现提供了关于SRSF1在结合体组装及其调节中的作用的见解.
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