Alternative Polyadenylation Utilization Results in Ribosome Assembly and mRNA Translation Deficiencies in a Model for Muscle Aging.
Alternative polyadenylation
Miscellaneous RNAs
PABPN1
Translatome
mRNA processing
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
01 06 2022
01 06 2022
Historique:
received:
09
11
2021
pubmed:
5
3
2022
medline:
7
6
2022
entrez:
4
3
2022
Statut:
ppublish
Résumé
Aging-associated muscle wasting is regulated by multiple molecular processes, whereby aberrant mRNA processing regulation induces muscle wasting. The poly(A)-binding protein nuclear 1 (PABPN1) regulates polyadenylation site (PAS) utilization, in the absence of PABPN1 the alternative polyadenylation (APA) is utilized. Reduced PABPN1 levels induce muscle wasting where the expression of cellular processes regulating protein homeostasis, the ubiquitin-proteasome system, and translation, are robustly dysregulated. Translation is affected by mRNA levels, but PABPN1 impact on translation is not fully understood. Here we show that a persistent reduction in PABPN1 levels led to a significant loss of translation efficiency. RNA-sequencing of rRNA-depleted libraries from polysome traces revealed reduced mRNA abundance across ribosomal fractions, as well as reduced levels of small RNAs. We show that the abundance of translated mRNAs in the polysomes correlated with PAS switches at the 3'-UTR. Those mRNAs are enriched in cellular processes that are essential for proper muscle function. This study suggests that the effect of PABPN1 on translation efficiency impacts protein homeostasis in aging-associated muscle atrophy.
Identifiants
pubmed: 35245938
pii: 6542719
doi: 10.1093/gerona/glac058
pmc: PMC9159670
doi:
Substances chimiques
3' Untranslated Regions
0
Poly(A)-Binding Protein I
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1130-1140Subventions
Organisme : NIA NIH HHS
Pays : United States
Organisme : NIH HHS
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.
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