Collision-induced ribosome degradation driven by ribosome competition and translational perturbations

Individual stalling of catalytically inactive ribosomes at the start codon triggers ubiquitination of ribosomal protein uS3 and subsequent 18S rRNA decay. While collisions between ribosomes during translation elongation represent a more widespread form of translation perturbation, their impact on ribosome stability remains unknown. Here, we clarify a bifurcation in ubiquitination-mediated ribosome turnover, identifying a collision-induced branch of uS3 ubiquitination and small subunit destabilization in yeast. This pathway eliminates not only non-functional ribosomes but also translationally active ones with a prokaryotic-like decoding center, driven by competition with wild-type ribosomes due to differing translation rates. We further show that endogenous ribosomal subunit stoichiometry shifts toward a small-subunit-shortage state via ubiquitination upon perturbed translation triggered by the anti-cancer drug cisplatin and the growth phase transition. These findings reveal a mechanism by which ribosome dynamics generally affects ribosome stability, implicating ribosome dysfunction, heterogeneity, and stress-related translational disturbances in small subunit degradation.催化失活的核糖体在起始密码子处的单独停滞，会触发核糖体蛋白uS3的泛素化以及后续的18S核糖体RNA（18S rRNA）降解。尽管翻译延伸过程中核糖体之间的碰撞是更为普遍的翻译扰动形式，但它们对核糖体稳定性的影响仍未明确。本研究阐明了泛素化介导的核糖体周转的分支机制，在酵母中鉴定出一条由碰撞诱导的uS3泛素化与核糖体小亚基失稳通路。该通路不仅能够清除非功能性核糖体，还能清除带有原核生物样解码中心的翻译活性核糖体，其驱动因素为翻译速率差异导致的与野生型核糖体的竞争。我们进一步发现，在抗癌药物顺铂与生长阶段转换所触发的翻译扰动中，内源性核糖体亚基化学计量比会通过泛素化向小亚基短缺状态偏移。这些发现揭示了核糖体动态普遍影响核糖体稳定性的机制，将核糖体功能异常、异质性以及应激相关的翻译扰动与小亚基降解关联起来。