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Liao, Kuo-Chieh, Chuo, Vanessa, Fagg, W Samuel, Modahl, Cassandra, Widen, Steven and Garcia-Blanco, Mariano A (2021) 'The RNA binding protein Quaking represses splicing of the Fibronectin EDA exon and downregulates the interferon response'. Nucleic Acids Research, Vol 49, Issue 17, pp. 10034-10045.
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gkab732 cassie modahl 01.05.2024.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NOT_LSTM |
| Subjects: | QU Biochemistry > QU 4 General works QU Biochemistry > Genetics > QU 460 Genomics. Proteomics QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58.7 RNA |
| Faculty: Department: | Biological Sciences > Department of Tropical Disease Biology |
| Digital Object Identifer (DOI): | https://doi.org/10.1093/nar/gkab732 |
| Depositing User: | Clare O'Neill |
| Date Deposited: | 01 May 2024 12:46 |
| Last Modified: | 01 May 2024 12:46 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/24483 |
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