Defective ribosomal products challenge nuclear function by impairing nuclear condensate dynamics and immobilizing ubiquitin.
defective ribosomal products
membraneless organelles
molecular chaperones
nucleus
proteostasis
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
10
12
2018
revised:
05
06
2019
accepted:
07
06
2019
pubmed:
5
7
2019
medline:
24
12
2019
entrez:
5
7
2019
Statut:
ppublish
Résumé
Nuclear protein aggregation has been linked to genome instability and disease. The main source of aggregation-prone proteins in cells is defective ribosomal products (DRiPs), which are generated by translating ribosomes in the cytoplasm. Here, we report that DRiPs 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 DRiPs for later clearance. Whereas nucleoli serve as constitutive overflow compartments, PML bodies are stress-inducible overflow compartments for DRiPs. If DRiPs 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.
Identifiants
pubmed: 31271238
doi: 10.15252/embj.2018101341
pmc: PMC6669919
doi:
Substances chimiques
Molecular Chaperones
0
Ubiquitin
0
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e101341Subventions
Organisme : Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (AriSLA)
Pays : International
Organisme : Fondazione Cariplo (Cariplo Foundation)
ID : 2014-0703
Pays : International
Organisme : Ministero degli Affari Esteri e della Cooperazione Internazionale (MAECI)
Pays : International
Organisme : EU Joint Programme - Neurodegenerative Disease Research (JPND)
ID : 643417
Pays : International
Organisme : EMBO Long-Term fellowship
ID : ALTF 406-2017
Pays : International
Organisme : EC|H2020|H2020 Priority Excellent Science|H2020 European Research Council (ERC)
ID : 725836
Pays : International
Organisme : Bundesministerium für Bildung und Forschung (BMBF)
ID : 01ED1601A
Pays : International
Organisme : Bundesministerium für Bildung und Forschung (BMBF)
ID : 031A359A
Pays : International
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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