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PLoS Pathog. 2014 Mar 20;10(3):e1004012. doi: 10.1371/journal.ppat.1004012. eCollection 2014 Mar.

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

Author information

1
Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
2
Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan; Institute for Innovative NanoBio Drug Discovery and Development, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
3
Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chuo-ku, Chiba, Japan.
4
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
5
Department of Biochemistry I, School of Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.

Abstract

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).

PMID:
24651521
PMCID:
PMC3961341
DOI:
10.1371/journal.ppat.1004012
[Indexed for MEDLINE]
Free PMC Article
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