Wooters Haleigh C, Nimmagadda Neil C, Darnell Alicia M, Silva Gustavo M
Department of Biology, Duke University, Durham, NC 27708, USA.
Department of Pharmacology and Cancer Biology, School of Medicine, Duke University, Durham, NC 27708, USA.
Trends Biochem Sci. 2025 Jul 10. doi: 10.1016/j.tibs.2025.06.009.
It has become evident that a complex code of ribosome ubiquitination regulates protein synthesis, particularly in stress conditions. Ubiquitin is known largely for its role in protein stability; however, new high-throughput screening and advances in proteomics are underscoring its novel role as a master regulator of ribosome function. Still, much remains to be discovered about how this code acts and supports translation reprogramming in a context-specific manner. Here we discuss the nature of this code, the dynamics of site-specific ribosome ubiquitination, and the unique roles that multiple enzymes play in defining the translatome and cotranslational quality control pathways. We also provide insights on the importance of unraveling this code to understand the physiological impact of modified ribosome subpopulations in cellular stress and human disease.
越来越明显的是,一种复杂的核糖体泛素化密码调节着蛋白质合成,尤其是在应激条件下。泛素主要因其在蛋白质稳定性方面的作用而为人所知;然而,新的高通量筛选和蛋白质组学的进展正在凸显其作为核糖体功能主要调节因子的新作用。尽管如此,关于这个密码如何以特定背景的方式发挥作用并支持翻译重编程,仍有许多有待发现的地方。在这里,我们讨论这个密码的性质、位点特异性核糖体泛素化的动态变化,以及多种酶在定义翻译组和共翻译质量控制途径中所起的独特作用。我们还提供了关于解开这个密码对于理解修饰核糖体亚群在细胞应激和人类疾病中的生理影响的重要性的见解。