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,#,*
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.
Accession Number: S-BIAD1164
Publication status: Accepted at Molecular Cell
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