Pumilio-1 mediated translational control of claudin-5 at the blood-brain barrier.
Claudin-5
Pumilio
Tight junction
Translational regulation
Journal
Fluids and barriers of the CNS
ISSN: 2045-8118
Titre abrégé: Fluids Barriers CNS
Pays: England
ID NLM: 101553157
Informations de publication
Date de publication:
19 Jun 2024
19 Jun 2024
Historique:
received:
19
02
2024
accepted:
25
05
2024
medline:
20
6
2024
pubmed:
20
6
2024
entrez:
19
6
2024
Statut:
epublish
Résumé
Claudin-5 is one of the most essential tight junction proteins at the blood-brain barrier. A single nucleotide polymorphism rs10314 is located in the 3'-untranslated region of claudin-5 and has been shown to be a risk factor for schizophrenia. Here, we show that the pumilio RNA-binding protein, pumilio-1, is responsible for rs10314-mediated claudin-5 regulation. The RNA sequence surrounding rs10314 is highly homologous to the canonical pumilio-binding sequence and claudin-5 mRNA with rs10314 produces 25% less protein due to its inability to bind to pumilio-1. Pumilio-1 formed cytosolic granules under stress conditions and claudin-5 mRNA appeared to preferentially accumulate in these granules. Added to this, we observed granular pumilio-1 in endothelial cells in human brain tissues from patients with psychiatric disorders or epilepsy with increased/accumulated claudin-5 mRNA levels, suggesting translational claudin-5 suppression may occur in a brain-region specific manner. These findings identify a key regulator of claudin-5 translational processing and how its dysregulation may be associated with neurological and neuropsychiatric disorders.
Identifiants
pubmed: 38898501
doi: 10.1186/s12987-024-00553-5
pii: 10.1186/s12987-024-00553-5
doi:
Substances chimiques
Claudin-5
0
RNA-Binding Proteins
0
RNA, Messenger
0
CLDN5 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
52Subventions
Organisme : Science Foundation Ireland
ID : 21/RC/10294_P2
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 21/RC/10294_P2
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 21/RC/10294_P2
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 21/RC/10294_P2
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 21/RC/10294_P2
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 21/RC/10294_P2
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 21/RC/10294_P2
Pays : Ireland
Informations de copyright
© 2024. The Author(s).
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