Human DICER helicase domain recruits PKR and modulates its antiviral activity.
Fiche publication
Date publication
mai 2021
Journal
PLoS pathogens
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PFEFFER Sébastien, Mr HAMMANN Philippe
Tous les auteurs :
Montavon TC, Baldaccini M, Lefèvre M, Girardi E, Chane-Woon-Ming B, Messmer M, Hammann P, Chicher J, Pfeffer S
Lien Pubmed
Résumé
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.
Référence
PLoS Pathog. 2021 May;17(5):e1009549