RNA G-四重复 (rG4) 通过调解核糖体暂停来加剧细胞衰老
Haoxian Zhou1,2, Shu Wu2, Bin Li3
1Department of Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Protein & cell
|June 12, 2025
概括
细胞衰老涉及蛋白质失衡. 这项研究表明,RNA G-四复合体 (rG4s) 阻碍了翻译,增加了核糖体暂停和衰老,这对衰老有影响.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 蛋白质稳态的丧失是细胞衰老的一个关键特征.
- 核糖体暂停在衰老过程中显著导致蛋白质静止的崩.
- 核糖体暂停在衰老细胞中的特定作用需要进一步阐明.
研究的目的:
- 研究RNA G-四重复合体 (rG4s) 对衰老细胞翻译效率的影响.
- 探索rG4结构及其调节器在细胞衰老和衰老中的作用.
主要方法:
- 核糖体造型,以评估翻译效率.
- G-四重复RNA免疫沉降测序 (RIP-seq) 来映射rG4结构.
- 在体内和体内翻译试验.
- 在衰老细胞和老年小鼠中分析DHX9表达.
主要成果:
- 富含rG4基因的翻译效率在衰老细胞中降低.
- 编码序列中的rG4结构阻碍了翻译.
- 增加rG4的丰富性和稳定性加剧了细胞衰老.
- 衰老细胞中DHX9表达的减少导致核糖体暂停的增加.
- 年龄较大的小鼠表现出增加的rG4,受损的蛋白质稳定性和减少的DHX9.
结论:
- 在细胞衰老过程中,rG4结构在调节翻译和蛋白质稳定中发挥着重要作用.
- DHX9是rG4丰度的关键调节者,影响核糖体暂停.
- 准rG4s和DHX9可能提供延迟细胞衰老和衰老的策略.
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