Takehara Yuka, Yashiroda Hideki, Matsuo Yoshitaka, Zhao Xian, Kamigaki Akane, Matsuzaki Tetsuo, Kosako Hidetaka, Inada Toshifumi, Murata Shigeo
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
iScience. 2021 Feb 5;24(3):102145. doi: 10.1016/j.isci.2021.102145. eCollection 2021 Mar 19.
Ubiquitination is a major post-translational modification of ribosomal proteins. The role of ubiquitination in the regulation of ribosome functions is still being elucidated. However, the importance of ribosome deubiquitination remains unclear. Here, we show that the cycle of ubiquitination and deubiquitination of the 40S ribosome subunit eS7 is important for efficient translation. eS7 ubiquitination at lysine 83 is required for efficient protein translation. We identified Otu2 and Ubp3 as the deubiquitinating enzymes for eS7. An ΔΔ mutation caused a defect in protein synthesis. Ubp3 inhibited polyubiquitination of eS7 in polysomes to keep eS7 in a mono-ubiquitinated form, whereas Otu2 was specifically bound to the free 40S ribosome and promoted the dissociation of mRNAs from 40S ribosomes in the recycling step. Our results provide clues for understanding the molecular mechanism of the translation system via a ubiquitination-deubiquitination cycle.
泛素化是核糖体蛋白主要的翻译后修饰。泛素化在核糖体功能调控中的作用仍在阐明之中。然而，核糖体去泛素化的重要性仍不清楚。在此，我们表明40S核糖体亚基eS7的泛素化和去泛素化循环对高效翻译很重要。赖氨酸83处的eS7泛素化是高效蛋白质翻译所必需的。我们鉴定出Otu2和Ubp3为eS7的去泛素化酶。一个ΔΔ突变导致蛋白质合成缺陷。Ubp3抑制多核糖体中eS7的多泛素化，使eS7保持单泛素化形式，而Otu2特异性结合游离的40S核糖体，并在循环步骤中促进mRNA从40S核糖体上解离。我们的结果为通过泛素化-去泛素化循环理解翻译系统的分子机制提供了线索。
