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The RNA binding protein Quaking represses host interferon response by downregulating MAVS.
Liao, Kuo-Chieh; Chuo, Vanessa; Fagg, W Samuel; Bradrick, Shelton S; Pompon, Julien; Garcia-Blanco, Mariano A.
Afiliación
  • Liao KC; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
  • Chuo V; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
  • Fagg WS; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
  • Bradrick SS; Department of Surgery, Transplant Division, The University of Texas Medical Branch, Galveston, TX, USA.
  • Pompon J; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
  • Garcia-Blanco MA; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
RNA Biol ; 17(3): 366-380, 2020 03.
Article en En | MEDLINE | ID: mdl-31829086
Quaking (QKI) is an RNA-binding protein (RBP) involved in multiple aspects of RNA metabolism and many biological processes. Despite a known immune function in regulating monocyte differentiation and inflammatory responses, the degree to which QKI regulates the host interferon (IFN) response remains poorly characterized. Here we show that QKI ablation enhances poly(I:C) and viral infection-induced IFNß transcription. Characterization of IFN-related signalling cascades reveals that QKI knockout results in higher levels of IRF3 phosphorylation. Interestingly, complementation with QKI-5 isoform alone is sufficient to rescue this phenotype and reduce IRF3 phosphorylation. Further analysis shows that MAVS, but not RIG-I or MDA5, is robustly upregulated in the absence of QKI, suggesting that QKI downregulates MAVS and thus represses the host IFN response. As expected, MAVS depletion reduces IFNß activation and knockout of MAVS in the QKI knockout cells completely abolishes IFNß induction. Consistently, ectopic expression of RIG-I activates stronger IFNß induction via MAVS-IRF3 pathway in the absence of QKI. Collectively, these findings demonstrate a novel role for QKI in negatively regulating host IFN response by reducing MAVS levels.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / Proteínas de Unión al ARN / Proteínas Adaptadoras Transductoras de Señales / Interacciones Huésped-Patógeno Límite: Humans Idioma: En Revista: RNA Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / Proteínas de Unión al ARN / Proteínas Adaptadoras Transductoras de Señales / Interacciones Huésped-Patógeno Límite: Humans Idioma: En Revista: RNA Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos