Human DICER helicase domain recruits PKR and modulates its antiviral activity.
PLoS Pathog
; 17(5): e1009549, 2021 05.
Article
en 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.
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Antivirales
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Virus de los Bosques Semliki
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Replicación Viral
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Infecciones por Alphavirus
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EIF-2 Quinasa
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Ribonucleasa III
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ARN Helicasas DEAD-box
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Dominios y Motivos de Interacción de Proteínas
Idioma:
En
Revista:
PLoS Pathog
Año:
2021
Tipo del documento:
Article