K6链接的无处不在标志着甲诱导的RNA-蛋白交叉链接用于分辨率
Aldwin Suryo Rahmanto1, Christian J Blum2, Claudia Scalera2
1Institute of Molecular Biology (IMB), 55128 Mainz, Germany; Institute of Developmental Biology and Neurobiology (IDN), Johannes Gutenberg-Universität, 55128 Mainz, Germany.
Molecular cell
|November 11, 2023
概括
甲导致RNA-蛋白质交叉链接 (RPCs),通过阻断核糖体来阻止蛋白质合成. 涉及RNF14和VCP的细胞通路解决了这些RPC,减轻了化物毒性.
科学领域:
- 分子生物学分子生物学
- 细胞应激反应的应激反应
- 毒理学 毒理学 毒理学
背景情况:
- 反应性化物是新陈代谢和酒精消费的副产品,可以在组织中积累.
- 化物毒性主要与DNA损伤有关,抑制转录和复制.
- 化物在干扰其他细胞过程中的作用在很大程度上仍未被探索.
研究的目的:
- 为了调查反应性化物是否干扰细胞过程超越DNA损伤.
- 阐明甲影响蛋白质合成的机制.
- 为了确定参与响应甲诱导的细胞损伤的细胞机械.
主要方法:
- 利用人类细胞模型研究甲暴露的影响.
- 研究了甲诱导的RNA-蛋白交叉链接 (RPC) 以及它们对翻译的影响.
- 描述了涉及RNF14和VCP的无处不在和分辨路径.
主要成果:
- 证明甲会在人体细胞中诱导RNA-蛋白交叉链接 (RPC).
- 表明RPCs会阻断核糖体,导致翻译的抑制.
- 确定了一条RNF14在RPC上无处不在的途径,VCP解决了它们.
结论:
- 甲诱导的RPCs通过抑制翻译导致细胞毒性.
- 涉及RNF14和VCP的进化保守的应激反应途径保护细胞免受RPC积累.
- 这些发现表明RPCs在反应性化物的毒性中起着更广泛的作用.
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