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Defective ribosomal products challenge nuclear function by impairing nuclear condensate dynamics and immobilizing ubiquitin
Author(s) -
Mediani Laura,
GuillénBoixet Jordina,
Vinet Jonathan,
Franzmann Titus M,
Bigi Ilaria,
Mateju Daniel,
Carrà Arianna D,
Morelli Federica F,
Tiago Tatiana,
Poser Ina,
Alberti Simon,
Carra Serena
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018101341
Subject(s) - library science , humanities , biology , art history , philosophy , art , computer science
Nuclear protein aggregation has been linked to genome instability and disease. The main source of aggregation‐prone proteins in cells is defective ribosomal products ( DR iPs), which are generated by translating ribosomes in the cytoplasm. Here, we report that DR iPs rapidly diffuse into the nucleus and accumulate in nucleoli and PML bodies, two membraneless organelles formed by liquid–liquid phase separation. We show that nucleoli and PML bodies act as dynamic overflow compartments that recruit protein quality control factors and store DR iPs for later clearance. Whereas nucleoli serve as constitutive overflow compartments, PML bodies are stress‐inducible overflow compartments for DR iPs. If DR iPs are not properly cleared by chaperones and proteasomes due to proteostasis impairment, nucleoli undergo amyloidogenesis and PML bodies solidify. Solid PML bodies immobilize 20S proteasomes and limit the recycling of free ubiquitin. Ubiquitin depletion, in turn, compromises the formation of DNA repair compartments at fragile chromosomal sites, ultimately threatening cell survival.