细胞质扩大CAGRNA重复的凝抑制了全球蛋白质合成
Yuyin Pan1, Junmei Lu1, Xinran Feng1
1Neurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, New Cornerstone Science Laboratory, School of Life Sciences, Fudan University, Shanghai, China.
Nature chemical biology
|August 17, 2023
概括
扩展的CAG重复RNA形成细胞凝,损害蛋白质合成,导致亨廷顿病模型的缺陷. 破坏RNA凝可以拯救蛋白质合成,突出显示疾病中的RNA相变.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 扩展的CAG重复 (eCAGr) RNA可以经历相位过渡.
- 细胞中RNA凝的功能后果在很大程度上是未知的.
研究的目的:
- 为了研究eCAGrRNA凝在细胞内的功能影响.
- 探索RNA凝在CAG重复扩张障碍中的作用.
主要方法:
- 细胞成像观察RNA焦点的形成和降解.
- 生物化学测试用于测量全球蛋白质合成速率.
- 在体内研究使用敲进小鼠模型和腺相关病毒 (AAV) 输送.
主要成果:
- eCAGr RNA形成了细胞质凝状的焦点,被 lysosomes 降解.
- RNA凝显著降低了全球蛋白质合成,可能通过隔离eEF2.
- 破坏凝会恢复蛋白质合成;增强凝会使表型恶化.
- 在亨廷顿病模型和患者样本中观察到eEF2点的增加.
- 在小鼠中,神经元eCAGrRNA表达导致行为缺陷.
结论:
- 这项研究证明了细胞内RNA凝及其功能后果.
- RNA凝有助于CAG重复扩张疾病的病理生理学,如亨廷顿病.
- 研究结果提供了关于RNA相过渡在细胞功能和疾病中的作用的见解.
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