经由Hel2依赖的ubiquitin链标记的停滞不前的二位体在转化脱落时经历了Ubp2/Ubp3介导的二位素化
Mario Scazzari1, Ying Zhang1, Anna Moddemann1
1Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Communications biology
|January 28, 2025
概括
E3无素结合酶Hel2通过控制Rps20上的多素链长度来区分短暂和长期的核糖体停滞. 这种机制有助于核糖体相关质量控制 (RQC) 途径选择致命停滞的核糖体.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 停滞的核糖体会导致蛋白质合成问题和有害的截断.
- 细胞使用与核糖体相关的质量控制 (RQC) 和no-go mRNA衰变 (NGD) 途径来管理停滞的核糖体.
- 在酵母中,E3泛基因化酶 Hel2 准异体和三体,启动RQC/NGD路径.
研究的目的:
- 为了研究Hel2如何选择长期停滞的核糖体,在无压力细胞中的丰富的二胞体和三胞体中选择.
- 在体内定量分析Hel2•核糖体复合体和Rps20无化/脱化动态.
- 阐明Hel2区分暂时和持续的核糖体停滞的机制.
主要方法:
- 在体内Hel2•核糖体复合体的定量分析.
- 追踪Hel2依赖的Rps20无化和Ubp2/Ubp3依赖的双化动态.
- 根据Rps20无化水平和RQC组件Slh1参与,评估停滞的核糖体的分辨率.
主要成果:
- Hel2占用率从单体逐渐增加到二体和三体.
- 具有Rps20单或二均化的核糖体独立于Slh1.1进行分离.
- 带有三或四均化Rps20的核糖体不能独立于Slh1.1进行分解.
结论:
- 在Rps20上,Hel2将核糖体停滞时间转换为聚比基链长度.
- 这种多比基因化作为一个定时器,使RQC途径能够区分和准致命停滞的核糖体.
- 这些发现提出了一种新的蛋白质合成质量控制机制,优先去除持久停滞的核糖体.
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