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Updated: Jan 10, 2026

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

Published on: April 4, 2025

RNA G-四重复合体作为FUS相位分离的调节开关而起作用

Jenny L Carey¹, Miyuki Hayashi¹, Emily Welebob²

¹Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

bioRxiv : the preprint server for biology

|November 24, 2025

概括

RNA G四复合体 (rG4s) 可以控制FUS蛋白的相分离. 特定的rG4结构抑制有毒的FUS聚合,为神经退行性疾病提供了新的治疗策略.

科学领域:

生物化学生物化学
分子生物学分子生物学
神经科学是一个神经科学.

背景情况:

对于细胞功能,FUS蛋白经历液-液相分离 (LLPS).
异常的FUS阶段过渡与神经退行性疾病有关.
RNA寡核酸可以逆转有毒的FUS聚合,但它们的机制尚不清楚.

研究的目的:

为了确定调节FUS LLPS的RNA的结构决定因素.
为了研究RNA G-四复合体 (rG4s) 作为FUS阶段行为的调节者.
开发用于FUS相关疾病的基于RNA的治疗方法.

主要方法:

研究了rG4结构,度,长度和稳定性对FUS LLPS的影响.
利用生物信息管道发现了新的rG4抑制剂.
使用生物物理技术分析了FUS-RNA相互作用.

主要成果:

确定了rG4s作为FUS LLPS的强大的调节器.
证明rG4活动可以通过长度和稳定性来调整,在抑制和核化之间切换.
显示稳定rG4s抑制FUS组装并抵抗离子破坏.
发现短rG4s优先与可溶性FUS相互作用,促进分散.
发现了新的rG4抑制剂,可以逆转FUSLLPS和聚合.

结论:

rG4s是蛋白质相位行为的化学可编程调节器.
RNA二级结构决定了蛋白质凝聚物的功能结果.
rG4s提供了针对致病性FUS组件的基于RNA的治疗方法的蓝图.
建立了生物分子凝聚物的RNA控制的结构功能范式.

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