RRC ID 56190
Author Le 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.
Title Terminal uridylyltransferases target RNA viruses as part of the innate immune system.
Journal Nat Struct Mol Biol
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.
Volume 25(9)
Pages 778-786
Published 2018-9-1
DOI 10.1038/s41594-018-0106-9
PII 10.1038/s41594-018-0106-9
PMID 30104661
PMC PMC6130846
MeSH 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
IF 12.109
Times Cited 20
Resource
C.elegans tm1021 tm1098