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

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  • 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

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

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.

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