K29-linked free polyubiquitin chains affect ribosome biogenesis and direct ribosomal proteins to the intranuclear quality control compartment

Mol Cell. 2024 Jun 20;84(12):2337-2352.e9. doi: 10.1016/j.molcel.2024.05.018. Epub 2024 Jun 12.


Ribosome assembly requires precise coordination between the production and assembly of ribosomal components. Mutations in ribosomal proteins that inhibit the assembly process or ribosome function are often associated with ribosomopathies, some of which are linked to defects in proteostasis. In this study, we examine the interplay between several yeast proteostasis enzymes, including deubiquitylases (DUBs) Ubp2 and Ubp14, and E3 ligases Ufd4 and Hul5, and we explore their roles in the regulation of the cellular levels of K29-linked unanchored polyubiquitin (polyUb) chains. Accumulating K29-linked unanchored polyUb chains associate with maturing ribosomes to disrupt their assembly, activate the ribosome assembly stress response (RASTR), and lead to the sequestration of ribosomal proteins at the intranuclear quality control compartment (INQ). These findings reveal the physiological relevance of INQ and provide insights into mechanisms of cellular toxicity associated with ribosomopathies.

Keywords: DUB-E3 ligase interplay; intranuclear quality control compartment; protein aggregation; ribosome assembly stress response; ribosomopathies; ubiquitin homeostasis; unconventional K29-linked unanchored polyubiquitin chains.

MeSH terms

  • Cell Nucleus / metabolism
  • Polyubiquitin* / genetics
  • Polyubiquitin* / metabolism
  • Proteostasis
  • Ribosomal Proteins* / genetics
  • Ribosomal Proteins* / metabolism
  • Ribosomes* / genetics
  • Ribosomes* / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination


  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Polyubiquitin
  • Ubiquitin-Protein Ligases