Nonsense-mediated mRNA decay factor UPF1 promotes aggresome formation.
Nat Commun
; 11(1): 3106, 2020 06 19.
Article
de En
| MEDLINE
| ID: mdl-32561765
ABSTRACT
Nonsense-mediated mRNA decay (NMD) typifies an mRNA surveillance pathway. Because NMD necessitates a translation event to recognize a premature termination codon on mRNAs, truncated misfolded polypeptides (NMD-polypeptides) could potentially be generated from NMD substrates as byproducts. Here, we show that when the ubiquitin-proteasome system is overwhelmed, various misfolded polypeptides including NMD-polypeptides accumulate in the aggresome a perinuclear nonmembranous compartment eventually cleared by autophagy. Hyperphosphorylation of the key NMD factor UPF1 is required for selective targeting of the misfolded polypeptide aggregates toward the aggresome via the CTIF-eEF1A1-DCTN1 complex the aggresome-targeting cellular machinery. Visualization at a single-particle level reveals that UPF1 increases the frequency and fidelity of movement of CTIF aggregates toward the aggresome. Furthermore, the apoptosis induced by proteotoxic stresses is suppressed by UPF1 hyperphosphorylation. Altogether, our data provide evidence that UPF1 functions in the regulation of a protein surveillance as well as an mRNA quality control.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
ARN messager
/
Transactivateurs
/
RNA helicases
/
Proteasome endopeptidase complex
/
Réponse aux protéines mal repliées
/
Dégradation des ARNm non-sens
Limites:
Humans
Langue:
En
Journal:
Nat Commun
Sujet du journal:
BIOLOGIA
/
CIENCIA
Année:
2020
Type de document:
Article