Human DICER helicase domain recruits PKR and modulates its antiviral activity.
PLoS Pathog
; 17(5): e1009549, 2021 05.
Article
in En
| MEDLINE
| ID: mdl-33984068
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Semliki forest virus
/
Virus Replication
/
Alphavirus Infections
/
EIF-2 Kinase
/
Ribonuclease III
/
DEAD-box RNA Helicases
/
Protein Interaction Domains and Motifs
Limits:
Humans
Language:
En
Journal:
PLoS Pathog
Year:
2021
Document type:
Article
Affiliation country:
Francia