Journal
EMBO JOURNAL
Volume 38, Issue 15, Pages -Publisher
WILEY
DOI: 10.15252/embj.2018101341
Keywords
defective ribosomal products; membraneless organelles; molecular chaperones; nucleus; proteostasis
Categories
Funding
- AriSLA Foundation
- Cariplo Foundation [2014-0703]
- MAECI (Dissolve_ALS)
- MIUR (Departments of excellence 2018-2022) [E91I18001480001]
- JPND
- European Union's Horizon 2020 Research and Innovation Programme [643417]
- Max Planck Society
- ERC [725836]
- BMBF [01ED1601A, 031A359A]
- EMBO Long-Term fellowship [ALTF 406-2017]
- H2020 Societal Challenges Programme [643417] Funding Source: H2020 Societal Challenges Programme
- European Research Council (ERC) [725836] Funding Source: European Research Council (ERC)
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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.
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