Ribosomal mistranslation leads to silencing of the unfolded protein response and increased mitochondrial biogenesis.
Commun Biol
; 2: 381, 2019.
Article
em En
| MEDLINE
| ID: mdl-31637312
ABSTRACT
Translation fidelity is the limiting factor in the accuracy of gene expression. With an estimated frequency of 10-4, errors in mRNA decoding occur in a mostly stochastic manner. Little is known about the response of higher eukaryotes to chronic loss of ribosomal accuracy as per an increase in the random error rate of mRNA decoding. Here, we present a global and comprehensive picture of the cellular changes in response to translational accuracy in mammalian ribosomes impaired by genetic manipulation. In addition to affecting established protein quality control pathways, such as elevated transcript levels for cytosolic chaperones, activation of the ubiquitin-proteasome system, and translational slowdown, ribosomal mistranslation led to unexpected responses. In particular, we observed increased mitochondrial biogenesis associated with import of misfolded proteins into the mitochondria and silencing of the unfolded protein response in the endoplasmic reticulum.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribossomos
/
Biogênese de Organelas
/
Resposta a Proteínas não Dobradas
Limite:
Humans
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suíça