TDP-43 suppresses tau expression via promoting its mRNA instability.
Nucleic Acids Res
; 45(10): 6177-6193, 2017 Jun 02.
Article
en En
| MEDLINE
| ID: mdl-28335005
ABSTRACT
In the brains of individuals with Alzheimer's disease (AD) and chronic traumatic encephalopathy, tau pathology is accompanied usually by intracellular aggregation of transactive response DNA-binding protein 43 (TDP-43). However, the role of TDP-43 in tau pathogenesis is not understood. Here, we investigated the role of TDP-43 in tau expression in vitro and in vivo. We found that TDP-43 suppressed tau expression by promoting its mRNA instability through the UG repeats of its 3Î-untranslated region (3Î-UTR). The C-terminal region of TDP-43 was required for this function. Neurodegenerative diseases-causing TDP-43 mutations affected tau mRNA instability differentially, in that some promoted and others did not significantly affect tau mRNA instability. The expression levels of tau and TDP-43 were inverse in the frontal cortex and the cerebellum. Accompanied with cytoplasmic accumulation of TDP-43, tau expression was elevated in TDP-43M337V transgenic mouse brains. The level of TDP-43, which is decreased in AD brains, was found to correlate negatively with the tau level in human brain. Our findings indicate that TDP-43 suppresses tau expression by promoting the instability of its mRNA. Down-regulation of TDP-43 may be involved in the tau pathology in AD and related neurodegenerative disorders.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ARN Mensajero
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Regulación de la Expresión Génica
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Proteínas tau
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Estabilidad del ARN
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Proteínas de Unión al ADN
Límite:
Aged
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Aged80
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Animals
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Female
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Humans
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Male
Idioma:
En
Año:
2017
Tipo del documento:
Article