DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation.

RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon (IFN) responses. Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA (dsRNA)-dependent protein kinase (PKR) activation, which has been ...
shown to be essential for the formation of antiviral stress granule (avSG). We found that DHX36 and PKR form a complex in a dsRNA-dependent manner. By forming this complex, DHX36 facilitates dsRNA binding and phosphorylation of PKR through its ATPase/helicase activity. Using DHX36 KO-inducible MEF cells, we demonstrated that DHX36 deficient cells showed defect in IFN production and higher susceptibility in RNA virus infection, indicating the physiological importance of this complex in host defense. In summary, we identify a novel function of DHX36 as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR).
Mesh Terms:
Cytoplasmic Granules, DEAD Box Protein 58, DEAD-box RNA Helicases, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Gene Knockout Techniques, HEK293 Cells, HeLa Cells, Humans, Immunoprecipitation, RNA Virus Infections, RNA Viruses, RNA, Double-Stranded, RNA, Small Interfering, RNA, Viral, Receptors, Immunologic, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Stress, Physiological, Transfection, eIF-2 Kinase
PLoS Pathog
Date: Mar. 01, 2014
Download Curated Data For This Publication
233700
Switch View:
  • Interactions 3