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

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 and TUT7 (collectively called 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.