PMID:28335005

Citation	Gu, J, Wu, F, Xu, W, Shi, J, Hu, W, Jin, N, Qian, W, Wang, X, Iqbal, K, Gong, CX and Liu, F' (2017) TDP-43 suppresses tau expression via promoting its mRNA instability. Nucleic Acids Res. '
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 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.
Links	PubMed Online version:10.1093/nar/gkx175
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TADBP		GO:0061158: 3'-UTR-mediated mRNA destabilization	ECO:0000314:		P		Organism: Homo sapiens. Paper’s Protein Name: Transactive response DNA-binding protein 43 (TDP-43). UniProt’s Protein Name: TAR DNA-binding protein 43. Notes: This is seen in Figure 2B. The paper states that “to study whether TDP-43 promoted tau mRNA instability through the 3΄-UTR of the mRNA, we fused tau 3΄-UTR to the C-terminal of green fluorescence protein (GFP) to make pEGFP/tau 3΄-UTR plasmid. This plasmid allowed us to study the regulation of tau mRNA through its 3΄-UTR by measuring the expression of GFP.” As can be seen in Figure 2B, expression of GFP decreased with an increased dosage of the protein.	complete CACAO 12354

References

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