The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance IFN-β response

The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance IFN-β response
Title:
The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance IFN-β response
Other Titles:
Journal of Biological Chemistry
Publication Date:
25 February 2019
Citation:
Kim SS, Sze L, Liu C, Lam KP. The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response [published correction appears in J Biol Chem. 2019 Jun 14;294(24):9655]. J Biol Chem. 2019;294(16):6430–6438. doi:10.1074/jbc.RA118.005868
Abstract:
RIG-I senses viral RNA in the cytosol and initiates host innate immune response by triggering the production of type 1 interferon. A recent RNAi knockdown screen yielded close to hundred host genes whose products affected viral RNA-induced IFN-β production and highlighted the complexity of the antiviral response. The stress granule protein G3BP1, known to arrest mRNA translation, was identified as a regulator of RIG-I-induced IFN-β production. How G3BP1 functions in RIG-I signaling is not known, however. Here, we overexpress G3BP1 with RIG-I in HEK293T cells and found that G3BP1 significantly enhances RIG-I-induced ifn-b mRNA synthesis. More importantly, we demonstrate that G3BP1 binds RIG-I and that this interaction involves the C-terminal RGG domain of G3BP1. Confocal microscopy studies also show G3BP1 co-localization with RIG-I and with infecting vesicular stomatitis virus in Cos-7 cells. Interestingly, immunoprecipitation studies using biotin-labeled viral dsRNA or poly(I·C) and cell lysate-derived or in vitro translated G3BP1 indicated that G3BP1 could directly bind these substrates and again via its RGG domain. Computational modeling further revealed a juxtaposed interaction between G3BP1 RGG and RIG-I RNA-binding domains. Together, our data reveal G3BP1 as a critical component of RIG-I signaling and possibly acting as a co-sensor to promote RIG-I recognition of pathogenic RNA.
License type:
PublisherCopyrights
Funding Info:
This research is supported by Bioprocessing Technology Institute, A*STAR
Description:
This research was originally published in the Journal of Biological Chemistry. Susana Soo-Yeon Kim, Lynette Sze and Kong-Peng Lam. The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance IFN-β response. J Biol Chem. 2019; Vol 294:6430-6438. © the American Society for Biochemistry and Molecular Biology.
ISSN:
0021-9258
1083-351X
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