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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)778-786
Number of pages9
JournalNature Structural & Molecular Biology
Volume25
Issue number9
DOIs
Publication statusPublished - 13 Aug 2018

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