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

Nat Struct Mol Biol. 2018 Sep;25(9):778-786. doi: 10.1038/s41594-018-0106-9. Epub 2018 Aug 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / virology*
  • Humans
  • Immunity, Innate*
  • RNA Interference
  • RNA Nucleotidyltransferases / metabolism*
  • RNA Viruses / immunology
  • RNA Viruses / metabolism*
  • RNA Viruses / physiology
  • RNA, Viral / metabolism
  • Transcriptome
  • Virus Replication


  • RNA, Viral
  • RNA Nucleotidyltransferases
  • UTP-RNA uridylyltransferase