Terminal uridylyltransferases target RNA viruses as part of the innate immune system.
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Authors
Le Pen, Jérémie
Jiang, Hongbing
Di Domenico, Tomás
Kosałka, Joanna
Leung, Christian
Morgan, Marcos
Wang, David
Publication Date
2018-09Journal Title
Nat Struct Mol Biol
ISSN
1545-9993
Publisher
Springer Science and Business Media LLC
Volume
25
Issue
9
Pages
778-786
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Le Pen, J., Jiang, H., Di Domenico, T., Kneuss, E., Kosałka, J., Leung, C., Morgan, M., et al. (2018). Terminal uridylyltransferases target RNA viruses as part of the innate immune system.. Nat Struct Mol Biol, 25 (9), 778-786. https://doi.org/10.1038/s41594-018-0106-9
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.
Keywords
A549 Cells, Animals, Caenorhabditis elegans, Humans, Immunity, Innate, RNA Interference, RNA Nucleotidyltransferases, RNA Viruses, RNA, Viral, Transcriptome, Virus Replication
Sponsorship
CRUK, The Wellcome Trust & ERC
Funder references
Cancer Research Uk (None)
European Research Council (260688)
Wellcome Trust (104640/Z/14/Z)
Cancer Research UK (18583)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (093970/Z/10/Z)
Wellcome Trust (102452/Z/13/Z)
Cancer Research Uk (None)
Identifiers
External DOI: https://doi.org/10.1038/s41594-018-0106-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283341
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