dsRNA-induced condensation of antiviral proteins modulates PKR activity.
Proc Natl Acad Sci U S A
; 119(33): e2204235119, 2022 08 16.
Article
en En
| MEDLINE
| ID: mdl-35939694
ABSTRACT
Mammalian cells respond to dsRNA in multiple manners. One key response to dsRNA is the activation of PKR, an eIF2α kinase, which triggers translational arrest and the formation of stress granules. However, the process of PKR activation in cells is not fully understood. In response to increased endogenous or exogenous dsRNA, we observed that PKR forms novel cytosolic condensates, referred to as dsRNA-induced foci (dRIFs). dRIFs contain dsRNA, form in proportion to dsRNA, and are enhanced by longer dsRNAs. dRIFs enrich several other dsRNA-binding proteins, including ADAR1, Stau1, NLRP1, and PACT. Strikingly, dRIFs correlate with and form before translation repression by PKR and localize to regions of cells where PKR activation is initiated. We hypothesize that dRIF formation is a mechanism that cells use to enhance the sensitivity of PKR activation in response to low levels of dsRNA or to overcome viral inhibitors of PKR activation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Virosis
/
ARN Bicatenario
/
ARN Viral
/
EIF-2 Quinasa
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2022
Tipo del documento:
Article