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To illuminate these roles, we performed genome scale transcriptome profiling in QKI knockout cells with or without poly(I:C) transfection, a double-stranded RNA analog that mimics viral infection. Analysis of RNA-sequencing data shows that QKI knockout upregulates genes induced by interferons, suggesting that QKI is an immune suppressor. Furthermore, differential splicing analysis shows that QKI primarily controls cassette exons, and among these events, we noted that QKI silences splicing of the extra domain A (EDA) exon in fibronectin (FN1) transcripts. QKI knockout results in elevated production and secretion of FN1-EDA protein, which is a known activator of interferons. Consistent with an upregulation of the interferon response in QKI knockout cells, our results show reduced production of dengue virus-2 and Japanese encephalitis virus in these cells. In conclusion, we demonstrate that QKI downregulates the interferon system and attenuates the antiviral state.<\/jats:p>","DOI":"10.1093\/nar\/gkab732","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T20:40:06Z","timestamp":1629232806000},"page":"10034-10045","source":"Crossref","is-referenced-by-count":14,"title":["The RNA binding protein Quaking represses splicing of the Fibronectin EDA exon and downregulates the interferon response"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8766-4824","authenticated-orcid":false,"given":"Kuo-Chieh","family":"Liao","sequence":"first","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore\u00a0169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Chuo","sequence":"additional","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore\u00a0169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2909-1666","authenticated-orcid":false,"given":"W\u00a0Samuel","family":"Fagg","sequence":"additional","affiliation":[{"name":"Transplant Division, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra\u00a0M","family":"Modahl","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Singapore, Singapore\u00a0119077, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Widen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8538-1997","authenticated-orcid":false,"given":"Mariano\u00a0A","family":"Garcia-Blanco","sequence":"additional","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore\u00a0169857, Singapore"},{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"2021092511315385200_B1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1089\/jir.2013.0117","article-title":"Post-transcriptional regulation of interferons and their signaling pathways","volume":"34","author":"Savan","year":"2014","journal-title":"J. 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