DHX36 Enhances RIG-I Signaling by Facilitating PKR-Mediated Antiviral Stress Granule Formation: e1004012

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)
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
Deoxyribonucleic acid
DNA
Gene expression
Homeostasis
Immune system
Infections
Interferon
Kinases
Phosphorylation
Proteins
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:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004012