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13.08.18 Antiviral gene screen in C elegans reveals third mechanism for antiviral defence

last modified Aug 15, 2018 04:18 PM
The Miska lab, with UK and USA collaborators, developed a system for antiviral gene discovery and identified 3'-terminal uridylation of viral RNAs as a defence mechanism in animals
13.08.18 Antiviral gene screen in C elegans reveals third mechanism for antiviral defence

Fig 5 extract: CDE-1 marks viral RNAs with a 3ʹ-U tail, which recruits 5ʹ-to-3ʹ exonucleases of the XRN family and 3ʹ-to-5ʹ exonucleases of the exosome complex

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

Le Pen et al. (2018) Nat Struct Mol Biol. Aug 13. DOI: 10.1038/s41594-018-0106-9. [Epub ahead of print]


Abstract from the paper

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.



Read more about research in the Miska lab.

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