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

TitleTerminal uridylyltransferases target RNA viruses as part of the innate immune system.
Publication TypeJournal Article
Year of Publication2018
AuthorsLe Pen J, Jiang H, Di Domenico T, Kneuss E, Kosałka J, Leung C, Morgan M, Much C, Rudolph KLM, Enright AJ, O'Carroll D, Wang D, Miska EA
JournalNat Struct Mol Biol
Volume25
Issue9
Pagination778-786
Date Published2018 Sep
ISSN1545-9985
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.

DOI10.1038/s41594-018-0106-9
Alternate JournalNat. Struct. Mol. Biol.
PubMed ID30104661
PubMed Central IDPMC6130846
Grant List / / Wellcome Trust / United Kingdom
Publication institute
CRM