The RNA binding protein Quaking represses splicing of the Fibronectin EDA exon and downregulates the interferon response.

Journal Article (Journal Article)

Quaking (QKI) controls RNA metabolism in many biological processes including innate immunity, where its roles remain incompletely understood. 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.

Full Text

Duke Authors

Cited Authors

  • Liao, K-C; Chuo, V; Fagg, WS; Modahl, CM; Widen, S; Garcia-Blanco, MA

Published Date

  • September 27, 2021

Published In

Volume / Issue

  • 49 / 17

Start / End Page

  • 10034 - 10045

PubMed ID

  • 34428287

Pubmed Central ID

  • PMC8464043

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

Digital Object Identifier (DOI)

  • 10.1093/nar/gkab732

Language

  • eng

Conference Location

  • England