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...

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Bibliographic Details
Published in:PLoS pathogens 2014-03, Vol.10 (3), p.e1004012-e1004012
Main Authors: Yoo, Ji-Seung, Takahasi, Kiyohiro, Ng, Chen Seng, Ouda, Ryota, Onomoto, Koji, Yoneyama, Mitsutoshi, Lai, Janice Ching, Lattmann, Simon, Nagamine, Yoshikuni, Matsui, Tadashi, Iwabuchi, Kuniyoshi, Kato, Hiroki, Fujita, Takashi
Format: Article
Language:English
Subjects:
Binding sites
Biology
Cellular signal transduction
Cytoplasmic Granules - immunology
DEAD Box Protein 58
DEAD-box RNA Helicases - immunology
DEAD-box RNA Helicases - metabolism
Deoxyribonucleic acid
DNA
eIF-2 Kinase - immunology
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Gene expression
Gene Knockout Techniques
Health aspects
HEK293 Cells
HeLa Cells
Homeostasis
Host-parasite relationships
Humans
Immune system
Immunoprecipitation
Infections
Interferon
Kinases
Phosphorylation
Protein kinases
Protein research
Proteins
Receptors, Immunologic
Reverse Transcriptase Polymerase Chain Reaction
RNA Virus Infections - immunology
RNA Viruses - immunology
RNA, Double-Stranded - immunology
RNA, Small Interfering - genetics
RNA, Viral - immunology
Signal Transduction - immunology
Stress, Physiological
Transfection
Viral infections
Viruses
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Summary: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).
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004012