PT  - JOURNAL ARTICLE
AU  - Jérémie Le Pen
AU  - Hongbing Jiang
AU  - Tomás Di Domenico
AU  - Emma Kneuss
AU  - Joanna Kosałka
AU  - Marcos Morgan
AU  - Christian Much
AU  - Konrad L. M. Rudolph
AU  - Anton J. Enright
AU  - Dónal O’Carroll
AU  - David Wang
AU  - Eric A. Miska
TI  - Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals
AID  - 10.1101/209114
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 209114
4099  - http://biorxiv.org/content/early/2017/12/19/209114.short
4100  - http://biorxiv.org/content/early/2017/12/19/209114.full
AB  - 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 C. elegans and its natural pathogen, the Orsay virus (OrV), and identified cde-1 as important for antiviral defense. CDE-1 is a homologue of the mammalian TUT4/7 terminal uridylyltransferases; its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3′ end of the OrV RNA genome and promotes its degradation, independently of the RNAi pathway. Likewise, TUT4/7 uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4/7 leads to increased IAV mRNA and protein levels. We have defined 3′ terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.