Human DICER helicase domain recruits PKR and modulates its antiviral activity

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 be...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC8118307 The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1009549