Terminal uridylyltransferases target RNA viruses as part of the innate immune system.
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RNA viruses are a major threat to animals and plants. RNA interference (RNAi) and the interferon response provide innate antiviral defense against RNA viruses. Here, we performed a large-scale screen using Caenorhabditis elegans and its natural pathogen the Orsay virus (OrV), and we identified cde-1 as important for antiviral defense. CDE-1 is a homolog of the mammalian TUT4 and TUT7 terminal uridylyltransferases (collectively called TUT4(7)); its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3' end of the OrV RNA genome and promotes its degradation in a manner independent of the RNAi pathway. Likewise, TUT4(7) enzymes uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4(7) leads to increased IAV mRNA and protein levels. Collectively, these data implicate 3'-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.
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1545-9985
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European Research Council (260688)
Wellcome Trust (104640/Z/14/Z)
Cancer Research UK (18583)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (093970/Z/10/Z)
Wellcome Trust (102452/Z/13/Z)
Cancer Research Uk (None)