Protein products of nonstop mRNA disrupt nucleolar homeostasis.
LTN1
Nonstop mRNA
Nucleolus
Phase separation
Protein quality control
Ribosome-associated quality control (RQC)
Journal
Cell stress & chaperones
ISSN: 1466-1268
Titre abrégé: Cell Stress Chaperones
Pays: Netherlands
ID NLM: 9610925
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
04
12
2020
accepted:
15
02
2021
revised:
10
02
2021
pubmed:
24
2
2021
medline:
27
1
2022
entrez:
23
2
2021
Statut:
ppublish
Résumé
Stalled mRNA translation results in the production of incompletely synthesized proteins that are targeted for degradation by ribosome-associated quality control (RQC). Here we investigated the fate of defective proteins translated from stall-inducing, nonstop mRNA that escape ubiquitylation by the RQC protein LTN1. We found that nonstop protein products accumulated in nucleoli and this localization was driven by polylysine tracts produced by translation of the poly(A) tails of nonstop mRNA. Nucleolar sequestration increased the solubility of invading proteins but disrupted nucleoli, altering their dynamics, morphology, and resistance to stress in cell culture and intact flies. Our work elucidates how stalled translation may affect distal cellular processes and may inform studies on the pathology of diseases caused by failures in RQC and characterized by nucleolar stress.
Identifiants
pubmed: 33619693
doi: 10.1007/s12192-021-01200-w
pii: 10.1007/s12192-021-01200-w
pmc: PMC8065075
doi:
Substances chimiques
RNA, Messenger
0
Saccharomyces cerevisiae Proteins
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
549-561Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR074875
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS084412
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115968
Pays : United States
Organisme : NIH HHS
ID : R01AR0748750
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS083417
Pays : United States
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