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- W2903569556 abstract "TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein, whose loss-of-function mutation causes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Recent studies demonstrated that TDP-43 binds to the 3' untranslated region (UTR) of target mRNAs to promote mRNA instability. Here, we show that TDP-43 recruits Caf1 deadenylase to mRNA targets and accelerates their deadenylation. Tethering TDP-43 to the mRNA 3'UTR recapitulates destabilization of the mRNA, and TDP-43 accelerates their deadenylation. This accelerated deadenylation is inhibited by a dominant negative mutant of Caf1. We find that TDP-43 physically interacts with Caf1. In addition, we provide evidence that TDP-43 regulates poly(A) tail length of endogenous Progranulin (GRN) mRNA. These results may shed light on the link between dysregulation of TDP-43-mediated mRNA deadenylation and pathogenesis of neurodegenerative diseases." @default.
- W2903569556 created "2018-12-22" @default.
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- W2903569556 date "2019-01-25" @default.
- W2903569556 modified "2023-10-12" @default.
- W2903569556 title "TDP ‐43 accelerates deadenylation of target mRNA s by recruiting Caf1 deadenylase" @default.
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- W2903569556 doi "https://doi.org/10.1002/1873-3468.13310" @default.
- W2903569556 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30520513" @default.
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