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

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

Author information

1
Gurdon Institute, University of Cambridge, Cambridge, UK.
2
Department of Biochemistry, University of Cambridge, Cambridge, UK.
3
Department of Genetics, University of Cambridge, Cambridge, UK.
4
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
5
Departments of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
6
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
7
Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
8
Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK.
9
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
10
European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy.
11
EMBL, European Bioinformatics Institute (EBI), Hinxton, UK.
12
Gurdon Institute, University of Cambridge, Cambridge, UK. eam29@cam.ac.uk.
13
Department of Genetics, University of Cambridge, Cambridge, UK. eam29@cam.ac.uk.
14
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK. eam29@cam.ac.uk.

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.

PMID:
30104661
PMCID:
PMC6130846
DOI:
10.1038/s41594-018-0106-9
[Indexed for MEDLINE]
Free PMC Article

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