bioRxiv 2023.05.03.539259; doi:
K29-linked unanchored polyubiquitin chains affect ribosome biogenesis and direct ribosomal proteins to the Intranuclear Quality control compartment (INQ)

Harsha Garadi Suresh1,#, Eric Bonneil2, Benjamin Albert3,4, Carine Dominique4, Michael Costanzo1, Carles Pons5, Myra Paz David Masinas1, Ermira Shuteriqi1, David Shore3, Anthony K. Henras4, Pierre Thibault2,6, Charles Boone1,7,#, and Brenda J. Andrews1,7,#,*

  • 1Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada
  • 2Institute for Research in Immunology and Cancer (IRIC)Université de Montréal, Montréal, Quebec H3C 3J7, Canada.
  • 3Department of Molecular Biology, Institute of Genetics and Genomics of Geneva (iGE3), Geneva, Switzerland
  • 4Molecular, Cellular and Developmental Biology Unit (MCD), Centre for Integrative Biology (CBI), University of Toulouse, CNRS, UPS, Toulouse France
  • 5Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain
  • 6Department of Chemistry, Université de Montréal, Montréal, Quebec H3C 3J7, Canada
  • 7Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada

  • # Corresponding authors:,,
  • * Lead contact:


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.

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Accession Number: S-BIAD1164

Publication status: Accepted at Molecular Cell

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