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可视化 TERRA RNA G-四重复在 FUS 生物分子凝聚物中展开
Tongyin Zheng1, Nicolas L Fawzi1
1Department of Molecular Biology, Cell Biology & Biochemistry and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence RI USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
RNA G四复合体 (rG4s) 是稳定的结构. FUS蛋白质凝结物展开这些rG4s,解释了它们在细胞中的明显不稳定性,并揭示了相位分离如何调节RNA功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- RNA G四复合体 (rG4s) 是稳定的RNA结构,对基因调节至关重要.
- 由于检测挑战,细胞rG4的行为受到争论.
- RNA结合蛋白FUS形成凝结物,可能会影响RNA结构.
研究的目的:
- 研究FUS凝结物如何影响TERRA的结构,这是一个模型rG4RNA.
- 确定FUS结合或相分离是否会改变rG4的稳定性.
- 阐明分相环境在调节RNA结构和功能的作用.
主要方法:
- 溶液NMR光谱学被用于研究TERRA rG4结构.
- 使用FUS低复杂度和RGG域 (FUS LC-RGG1) 来形成凝结物.
- 在稀释溶液和FUS凝结物中分析了TERRARNA结构.
主要成果:
- 在溶液中,FUS LC-RGG1将TERRA结合在一起,扰乱但不破坏rG4结构.
- 在FUS凝聚物中,TERRA rG4签名消失,表明展开.
- 至少三分之一的TERRARNA在FUS凝聚物中展开,即使在稳定缓冲条件下.
结论:
- 细胞凝结物可以将rG4s的结构组合转移到展开的状态.
- 这种展开的机制可能解释了在体内观察到的rG4s的不稳定性.
- 像FUS这样的蛋白质的相分离积极调节RNA结构和功能.
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