富含氨酸/氨酸的蛋白质和U2AF1相互作用的酸化依赖调节在早期的结合体组件组件中
Zihan Zhang1, Puspa Kunwar1, Yanbao Yu2
1Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
The Journal of biological chemistry
|February 4, 2026
概括
酸化通过控制氨酸/氨酸丰富 (SR) 蛋白和U2AF1.1之间的相互作用来调节结合体组合. 这项研究揭示了一种通过酸化依赖结合来调节早期结合体形成的保存机制.
科学领域:
- 分子生物学分子生物学
- 在RNA分离过程中.
- 蛋白质与蛋白质的相互作用
背景情况:
- 早期的结合体组合对于基因表达调节至关重要.
- 富含氨酸/氨酸 (SR) 的蛋白质和U2AF1是mRNA前拼接的关键调节者.
- 由于U2AF1的不溶性,SR蛋白-U2AF1相互作用的分子基础以前尚不清楚.
研究的目的:
- 研究SR蛋白和U2AF1.1.之间相互作用的分子机制.
- 阐明酸化在调节这些相互作用中的作用.
- 为了理解对合体组装的更广泛影响.
主要方法:
- 全长版U2AF1.1的重新折叠和溶解.
- 使用生物物理方法研究U2AF1和SRSF1之间的相互作用.
- 对U2AF1.1.的细胞酸化分析.
- 分子动力学 (MD) 模拟.分子动力学 (MD) 模拟.
主要成果:
- U2AF1的C端RS域 (RSU2AF1) 与酸化的SRSF1 (RSSRSF1) 相结合.
- RSU2AF1在细胞中被酸化,这种酸化降低了它对SRSF1的结合亲和力.
- 确定了SR蛋白和U2AF1之间的酸化依赖相互作用的保存机制,也解释了SR蛋白自我相互作用.
结论:
- 酸化是spliceosome组装因子相互作用的关键调节者.
- 一种涉及酸化依赖结合的保存机制控制了早期的结合体形成.
- 这些发现为RNA拼接调节提供了新的分子见解.
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