Human Dicer helicase domain recruits PKR and dsRNA binding proteins during viral infection

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Montavon, Thomas | Baldaccini, Morgane | Lefèvre, Mathieu | Girardi, Erika | Chane-Woon-Ming, Béatrice | Messmer, Mélanie | Hammann, Philippe | Chicher, Johana | Pfeffer, Sébastien

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The antiviral innate immune response mainly involves type I interferon (IFN) in mammalian cells. The contribution of the RNA silencing machinery remains to be established, but several recent studies indicate that the ribonuclease DICER can generate viral siRNAs in specific conditions. It has also been proposed that type I IFN and RNA silencing could be mutually exclusive antiviral responses. In order to decipher the implication of DICER during infection of human cells with the Sindbis virus, we determined its interactome by proteomics analysis. We show that DICER specifically interacts with several double-stranded RNA binding proteins and RNA helicases during viral infection. In particular, proteins such as DHX9, ADAR-1 and the protein kinase RNA-activated (PKR) are enriched with DICER in virus-infected cells. We demonstrate the importance of DICER helicase domain in its interaction with PKR and showed that it has functional consequences for the cellular response to viral infection.

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