| Autor: |
Yosuke Hashimoto, Chris Greene, Nicole Hanley, Natalie Hudson, David Henshall, Kieron J. Sweeney, Donncha F. O’Brien, Matthew Campbell |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Fluids and Barriers of the CNS, Vol 21, Iss 1, Pp 1-16 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2045-8118 |
| DOI: |
10.1186/s12987-024-00553-5 |
| Popis: |
Abstract 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. Graphical Abstract |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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