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The RNA binding protein Quaking represses host interferon response by downregulating MAVS.

ABSTRACT: 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 IFNβ 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 IFNβ activation and knockout of MAVS in the QKI knockout cells completely abolishes IFNβ induction. Consistently, ectopic expression of RIG-I activates stronger IFNβ 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.

SUBMITTER: Liao KC

PROVIDER: S-EPMC6999638 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The RNA binding protein Quaking represses host interferon response by downregulating MAVS.

Liao Kuo-Chieh KC Chuo Vanessa V Fagg W Samuel WS Bradrick Shelton S SS Pompon Julien J Garcia-Blanco Mariano A MA

RNA biology 20191219 3

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 IFNβ transcription. Characterization of IFN-related signalling cascades reveals that QKI knockout re ...[more]

PMID: 31829086

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The RNA binding protein Quaking represses host interferon response by downregulating MAVS.

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The RNA binding protein Quaking represses host interferon response by downregulating MAVS.

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