揭示了SRSF1在RNA G-四重复合体的结合和展开中的新功能
Naiduwadura Ivon Upekala De Silva1, Nathan Lehman1, Talia Fargason1
1Department of Chemistry, College of Arts and Sciences, University of Alabama at Birmingham, CH266, 901 14th Street South, Birmingham, AL 35294-1240, USA.
Nucleic acids research
|April 3, 2024
概括
在ARPC2mRNA中,SRSF1蛋白与G-四重复结构结合并展开,揭示了除了拼接之外的基因表达调节中的新角色.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 基因法规 基因法规
背景情况:
- 通过拼接,SRSF1蛋白调节超过1500个mRNA转录.
- SRSF1有两个RNA识别动机 (RRMs) 和一个富含Arg/Ser (RS) 的区域.
- 以前,人们认为SRSF1 RRMs可以结合单链增强剂,而RS区域缺乏RNA结合特异性.
研究的目的:
- 为了研究SRSF1.1的RNA结合场景.
- 了解SRSF1与G-四重复 (GQ) 结构的相互作用.
- 探索SRSF1在通过GQ结构调节基因表达中的作用.
主要方法:
- 生物化学结合测试以确定RNA结合偏好.
- 福斯特共振能量转移 (FRET) 和循环二元化 (CD) 用于研究结构变化.
- 和转移差 (STD) 核磁共振以确定特定的核酸相互作用.
- 路西法酶试验用于评估对基因表达的功能影响.
主要成果:
- SRSF1的RS区域更喜欢 purin而不是pyrimidine.
- 通过使用RRMs和RS区域,SRSF1结合到ARPC2 mRNA G-四重复.
- SRSF1 展开了 ARPC2 GQ 结构,RS 开始展开,RRMs 协助.
- 在SRSF1 RS中的基残留物特别与GQ中的瓜基相互作用.
- SRSF1减轻了GQ介导的基因表达抑制.
结论:
- SRSF1与RNA G四复合体相互作用并展开,挑战了其RNA结合特异性的以前的概念.
- 通过解决GQ结构,SRSF1在调节基因表达方面发挥着新的作用.
- 这些发现扩大了对RNA拼接和翻译中的SR蛋白功能的理解.
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