2019
DOI: 10.1080/15476286.2019.1703069
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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… Show more

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Cited by 10 publications
(24 citation statements)
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References 76 publications
(99 reference statements)
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“…Among GSEA gene sets that significantly correlated with gene expression changes caused by QKI KO in the absence of poly(I:C) transfection, the second highest scoring was the MOSERLE_IFNA_RESPONSE gene set ( 43 ) (normalized enrichment score of 2.42 with FDR q -val = 0.002; Figure 1B , Supplementary Table S2 ). This analysis implied that QKI represses the expression of many genes induced by type I IFNs, which is consistent with our previous report that QKI suppresses IFN induction ( 26 ).…”
Section: Resultssupporting
confidence: 93%
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“…Among GSEA gene sets that significantly correlated with gene expression changes caused by QKI KO in the absence of poly(I:C) transfection, the second highest scoring was the MOSERLE_IFNA_RESPONSE gene set ( 43 ) (normalized enrichment score of 2.42 with FDR q -val = 0.002; Figure 1B , Supplementary Table S2 ). This analysis implied that QKI represses the expression of many genes induced by type I IFNs, which is consistent with our previous report that QKI suppresses IFN induction ( 26 ).…”
Section: Resultssupporting
confidence: 93%
“…To investigate the mechanisms by which QKI regulates host immunity, we performed genome scale transcriptome profiling in parental (WT) and QKI knock-out (QKO#3) HuH7 cells ( 26 ) activated by poly(I:C) transfection (Figure 1A ). RNA-seq data, which had an average depth of 75M reads per sample, were analyzed to identify differential expression and processing of transcripts.…”
Section: Resultsmentioning
confidence: 99%
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“…HuH7 cells were transfected using Lipofectamine2000 (ThermoFisher), according to the manufacturer's instructions. NKX2.5 GFP hESCs were co-transfected with pX458-sgQKI as described (Liao et al, 2020) or control empty vector along with pCEP-puro which contains a puromycin-resistance gene. One day later puromycin was added at 1 μg/ml and cells were selected for 3 days, and then expanded in the absence of puromycin.…”
Section: Cell Culturementioning
confidence: 99%
“…Interestingly, ILF3 was shown to participate to antiviral type I interferon response by promoting the expression of IFNB1 and interferon-stimulated gene (ISG) during host translational shutoff (Watson et al, 2020). QKI was shown to repress host interferon response by downregulating MAVS expression at a post-transcriptional level (Liao et al, 2020). This suggests that SARS-CoV2 has evolved several mechanisms to dampen the type I interferon response by targeting specific RBPs.…”
Section: Resultsmentioning
confidence: 99%