dsRNA-induced condensation of antiviral proteins promotes PKR activation

Mammalian cells respond to dsRNA in multiple manners. One key response to dsRNA is the activation of PKR, an eIF2 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 also enrich several other dsRNA-binding proteins including ADAR1, Stau1, NLRP1, and PACT. Strikingly, dRIFs correlate with and form prior to translation repression by PKR and localize to regions of cells where PKR activation is initiated. We suggest that dRIF formation is a mechanism cells utilize to enhance the sensitivity of PKR activation in response to low levels of dsRNA, or to overcome viral inhibitors of PKR activation.