Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
08 06 2021
08 06 2021
Historique:
received:
18
08
2020
accepted:
12
05
2021
entrez:
9
6
2021
pubmed:
10
6
2021
medline:
12
8
2021
Statut:
epublish
Résumé
Random errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy. Resulting transgenic mice were mosaic and showed a muscle-related phenotype with reduced grip strength. Analysis of gene expression in skeletal muscle using RNA-Seq revealed transcriptomic changes occurring in an age-dependent manner, involving an interplay of PGC1α, FOXO3, mTOR, and glucocorticoids as key signaling pathways, and finally resulting in activation of a muscle atrophy program. Our results highlight the relevance of translation accuracy, and show how disturbances thereof may contribute to age-related pathologies.
Identifiants
pubmed: 34103648
doi: 10.1038/s42003-021-02204-z
pii: 10.1038/s42003-021-02204-z
pmc: PMC8187632
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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