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

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