Human DICER helicase domain recruits PKR and modulates its antiviral activity

• Published in: PLoS pathogens Vol. 17; no. 5; p. e1009549
• Main Authors: Montavon, Thomas C, Baldaccini, Morgane, Lefèvre, Mathieu, Girardi, Erika, Chane-Woon-Ming, Béatrice, Messmer, Mélanie, Hammann, Philippe, Chicher, Johana, Pfeffer, Sébastien
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-05-2021; Public Library of Science (PLoS)
• Subjects: Antiviral activity; Biochemistry, Molecular Biology; Biology and Life Sciences; Biosynthesis; Cell cycle; Cloning; Cytokines; Development and progression; DNA helicase; Double-stranded RNA; Genetic aspects; Genomes; Health aspects; Immune response; Infections; Interferon; Kinases; Life Sciences; Mammalian cells; Mammals; Medicine and Health Sciences; Microscopy; Physiological aspects; Polyproteins; Protein kinases; Protein-protein interactions; Proteins; Research and Analysis Methods; Ribonuclease; RNA viruses; RNA-mediated interference; Stem cells; Structural proteins; Suppressors; Viral infections; Virus diseases; Virus research; Viruses; France
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1009549

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 alphaviruses such as the Sindbis virus and Semliki forest 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 that the helicase domain of DICER is essential for this interaction and that its deletion confers antiviral properties to this protein in an RNAi-independent, PKR-dependent, manner.