2. Academic Validation
  3. Collision-induced ribosome degradation driven by ribosome competition and translational perturbations

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

  • Nat Commun. 2025 Dec 12;16(1):11087. doi: 10.1038/s41467-025-66026-x.
Sihan Li 1 2,  Okuto Shounai 3,  Misaki Kato 3,  Ken Ikeuchi 3 4 5,  Toshifumi Inada 6 7
Affiliations

Affiliations

  • 1 Division of RNA and gene regulation, Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, Japan. [email protected].
  • 2 Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. [email protected].
  • 3 Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • 4 Creative Interdisciplinary Research Division, Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.
  • 5 Division of Organic- and Bio-materials Research, Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan.
  • 6 Division of RNA and gene regulation, Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, Japan. [email protected].
  • 7 Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. [email protected].
PMID: 41387539 DOI: 10.1038/s41467-025-66026-x
Abstract

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.

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