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Terminal uridylyltransferases target RNA viruses as part of the innate immune system | Nature Structural & Molecular Biology
Description:
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 3ʹ 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 3ʹ-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism. A screen for C. elegans antiviral-defense genes identifies a homolog of the mammalian TUT4(7) terminal uridylyltransferase genes and leads to the discovery of 3′-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.
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headline:Terminal uridylyltransferases target RNA viruses as part of the innate immune system
description: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 3ʹ 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 3ʹ-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism. A screen for C. elegans antiviral-defense genes identifies a homolog of the mammalian TUT4(7) terminal uridylyltransferase genes and leads to the discovery of 3â²-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.
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headline:Terminal uridylyltransferases target RNA viruses as part of the innate immune system
description: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 3ʹ 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 3ʹ-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism. A screen for C. elegans antiviral-defense genes identifies a homolog of the mammalian TUT4(7) terminal uridylyltransferase genes and leads to the discovery of 3â²-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.
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Membrane Biology
Biological Microscopy
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address:
name:Departments of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, St. Louis, USA
type:PostalAddress
type:Organization
name:Tomás Di Domenico
affiliation:
name:University of Cambridge
address:
name:Gurdon Institute, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:University of Cambridge
address:
name:Department of Genetics, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
address:
name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
type:PostalAddress
type:Organization
name:Spanish National Cancer Research Centre (CNIO)
address:
name:Spanish National Cancer Research Centre (CNIO), Madrid, Spain
type:PostalAddress
type:Organization
name:Emma Kneuss
url:http://orcid.org/0000-0003-0662-8539
affiliation:
name:University of Cambridge
address:
name:Gurdon Institute, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:University of Cambridge
address:
name:Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:Joanna KosaÅka
affiliation:
name:University of Cambridge
address:
name:Gurdon Institute, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:University of Cambridge
address:
name:Department of Genetics, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:Christian Leung
affiliation:
name:Washington University in St. Louis School of Medicine
address:
name:Departments of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, St. Louis, USA
type:PostalAddress
type:Organization
name:Marcos Morgan
affiliation:
name:University of Edinburgh
address:
name:MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
type:PostalAddress
type:Organization
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit
address:
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy
type:PostalAddress
type:Organization
name:Christian Much
url:http://orcid.org/0000-0002-1644-8200
affiliation:
name:University of Edinburgh
address:
name:MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
type:PostalAddress
type:Organization
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit
address:
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy
type:PostalAddress
type:Organization
name:Konrad L. M. Rudolph
url:http://orcid.org/0000-0002-9866-7051
affiliation:
name:University of Cambridge
address:
name:Gurdon Institute, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:University of Cambridge
address:
name:Department of Genetics, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
address:
name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
type:PostalAddress
type:Organization
name:Anton J. Enright
url:http://orcid.org/0000-0002-6090-3100
affiliation:
name:EMBL, European Bioinformatics Institute (EBI)
address:
name:EMBL, European Bioinformatics Institute (EBI), Hinxton, UK
type:PostalAddress
type:Organization
name:Dónal OâCarroll
url:http://orcid.org/0000-0002-8626-2217
affiliation:
name:University of Edinburgh
address:
name:MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
type:PostalAddress
type:Organization
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit
address:
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy
type:PostalAddress
type:Organization
name:David Wang
affiliation:
name:Washington University in St. Louis School of Medicine
address:
name:Departments of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, St. Louis, USA
type:PostalAddress
type:Organization
name:Eric A. Miska
url:http://orcid.org/0000-0002-4450-576X
affiliation:
name:University of Cambridge
address:
name:Gurdon Institute, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:University of Cambridge
address:
name:Department of Genetics, University of Cambridge, Cambridge, UK
type:PostalAddress
type:Organization
name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
address:
name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Gurdon Institute, University of Cambridge, Cambridge, UK
name:Department of Biochemistry, University of Cambridge, Cambridge, UK
name:Department of Genetics, University of Cambridge, Cambridge, UK
name:Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, USA
name:Departments of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, St. Louis, USA
name:Gurdon Institute, University of Cambridge, Cambridge, UK
name:Department of Genetics, University of Cambridge, Cambridge, UK
name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
name:Spanish National Cancer Research Centre (CNIO), Madrid, Spain
name:Gurdon Institute, University of Cambridge, Cambridge, UK
name:Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK
name:Gurdon Institute, University of Cambridge, Cambridge, UK
name:Department of Genetics, University of Cambridge, Cambridge, UK
name:Departments of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, St. Louis, USA
name:MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy
name:MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy
name:Gurdon Institute, University of Cambridge, Cambridge, UK
name:Department of Genetics, University of Cambridge, Cambridge, UK
name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
name:EMBL, European Bioinformatics Institute (EBI), Hinxton, UK
name:MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
name:European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy
name:Departments of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, St. Louis, USA
name:Gurdon Institute, University of Cambridge, Cambridge, UK
name:Department of Genetics, University of Cambridge, Cambridge, UK
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