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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.

 

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Read more about research in the Miska lab.

Watch Eric Miska describe his research on video.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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