@article{01e75ac05e944deeb4d5cb6126670bc9,
title = "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.",
keywords = "IFN, IRF3, MAVS, QKI, viral infection",
author = "Liao, {Kuo Chieh} and Vanessa Chuo and Fagg, {W. Samuel} and Shelton Bradrick and Julien Pompon and Mariano Garcia-Blanco",
note = "Funding Information: This research was supported by the National Research Foundation Singapore under its Cooperative Basic Research Grant(NMRC/CBRG/0074/2014); by the Singapore Ministry of Health{\textquoteright}s National Medical Research Council under its Young Individual Research Grant (NMRC/OFYIRG/0054/2017), and under its NMRC Zika Response Research Fund (NMRC/ZRRF/0007/2017) and by the Duke-NUS Medical School Signature Research Programme funded by the Agency for Science, Technology and Research (A*STAR), Singapore, and the Ministry of Health, Singapore. We thank Dr. Pradeep Bist at Duke-NUS Medical School, Singapore, for providing reagents for this study. We thank Drs. Shang Li and Muhammad Khairul Ramlee for their advice in creating CRISPR KO cell lines. We are grateful to Dr. Manoj Krishnan for reagents and critical discussion for this project. We also thank all members of the Pompon/Garcia-Blanco laboratory, Duke-NUS Medical School, and colleagues from Bradrick/Garcia-Blanco laboratory, University of Texas Medical Branch, for their input and suggestions during the course of this work. Publisher Copyright: {\textcopyright} 2019, {\textcopyright} 2019 Informa UK Limited, trading as Taylor & Francis Group.",
year = "2020",
month = mar,
day = "3",
doi = "10.1080/15476286.2019.1703069",
language = "English (US)",
volume = "17",
pages = "366--380",
journal = "RNA Biology",
issn = "1547-6286",
publisher = "Landes Bioscience",
number = "3",
}