Autophagy-dependent alternative splicing of ribosomal protein S24 produces a more stable isoform that aids in hypoxic cell survival.
autophagy
hypoxia
ribosome
splicing
stress
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
revised:
08
12
2023
received:
05
11
2023
accepted:
24
12
2023
medline:
12
3
2024
pubmed:
29
1
2024
entrez:
28
1
2024
Statut:
ppublish
Résumé
Cells remodel splicing and translation machineries to mount specialized gene expression responses to stress. Here, we show that hypoxic human cells in 2D and 3D culture models increase the relative abundance of a longer mRNA variant of ribosomal protein S24 (RPS24L) compared to a shorter mRNA variant (RPS24S) by favoring the inclusion of a 22 bp cassette exon. Mechanistically, RPS24L and RPS24S are induced and repressed, respectively, by distinct pathways in hypoxia: RPS24L is induced in an autophagy-dependent manner, while RPS24S is reduced by mTORC1 repression in a hypoxia-inducible factor-dependent manner. RPS24L produces a more stable protein isoform that aids in hypoxic cell survival and growth, which could be exploited by cancer cells in the tumor microenvironment.
Identifiants
pubmed: 38281767
doi: 10.1002/1873-3468.14804
doi:
Substances chimiques
Protein Isoforms
0
Ribosomal Proteins
0
RNA, Messenger
0
RPS24 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
503-520Subventions
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : 04807
Informations de copyright
© 2024 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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