单蛋白/RNA成像显示ZNF598是解决碰撞核糖体的限制因素
Ana C De La Cruz1,2, Garrett Tisdale1,2, Emily Nakayama1,2
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
The EMBO journal
|August 1, 2025
概括
核糖体相关蛋白质质量控制 (RQC) 识别了坏的mRNAs. ZNF598蛋白向碰撞的核糖体,作为RQC中的速度限制因子,以保持蛋白质质质.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 核糖体相关蛋白质质量控制 (RQC) 对细胞蛋白质稳定至关重要.
- ZNF598是RQC途径中的一个关键的E3泛素酶,准碰撞的核糖体.
- 通过ZNF598区分短暂和停滞的核糖体碰撞的机制尚不清楚.
研究的目的:
- 研究ZNF598如何识别和结合异常mRNA上的碰撞核糖体.
- 确定ZNF598作为RQC通路中的速率限制因子的作用.
- 探索ZNF598在正常和压力条件下维持蛋白质质量的参与.
主要方法:
- 开发了一种新的方法来可视化单个ZNF598与特定mRNAs结合.
- 同时评估mRNA翻译状态,使用内源标记ZNF598与HaloTag.
- 量化ZNF598在不同细胞条件下的招募动态,包括UV诱导的RNA损伤.
主要成果:
- ZNF598对RQC记者mRNA具有强烈的结合,多个ZNF598分子与单个mRNA进行结合.
- 过度表达ZNF598加速了核糖体清除,证实了它在RQC中的速度限制作用.
- ZNF598针对非异常mRNA的一个子集,这表明它在蛋白质组监测中发挥了更广泛的作用.
- 紫外线诱导的RNA损伤减少了ZNF598的招募,这表明在广泛的压力下它的能力有限.
结论:
- ZNF598识别的不仅仅是引领碰撞的核糖体,可能感知mRNA或核糖体队列特征.
- ZNF598是有效的RQC的关键速度限制因素.
- 通过向可能受损的mRNAs,ZNF598在维持蛋白质组完整性方面发挥着至关重要的作用,即使在非压力条件下也是如此.
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