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Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals

By Jérémie Le Pen, Hongbing Jiang, Tomás Di Domenico, Emma Kneuss, Joanna Kosałka, Marcos Morgan, Christian Much, Konrad L. M. Rudolph, Anton J Enright, Dónal O’Carroll, David Wang, Eric A. Miska

Posted 25 Oct 2017
bioRxiv DOI: 10.1101/209114

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 C. elegans and its natural pathogen, the Orsay virus (OrV), and identified cde-1 as important for antiviral defense. CDE-1 is a homologue of the mammalian TUT4/7 terminal uridylyltransferases; its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3′ end of the OrV RNA genome and promotes its degradation, independently of the RNAi pathway. Likewise, TUT4/7 uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4/7 leads to increased IAV mRNA and protein levels. We have defined 3′ terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.

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