| First Author | Gu J | Year | 2017 |
| Journal | Nucleic Acids Res | Volume | 45 |
| Issue | 10 | Pages | 6177-6193 |
| PubMed ID | 28335005 | Mgi Jnum | J:250252 |
| Mgi Id | MGI:5922975 | Doi | 10.1093/nar/gkx175 |
| Citation | Gu J, et al. (2017) TDP-43 suppresses tau expression via promoting its mRNA instability. Nucleic Acids Res 45(10):6177-6193 |
| abstractText | 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 3-untranslated region (3-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. |
