Liao K. C., Chuo V., Fagg W. S., Bradrick S. S., Pompon Julien, Garcia-Blanco M. A. (2020). The RNA binding protein Quaking represses host interferon response by downregulating MAVS. RNA Biology, 17 (3), 366-380. ISSN 1547-6286.
Titre du document
The RNA binding protein Quaking represses host interferon response by downregulating MAVS
Liao K. C., Chuo V., Fagg W. S., Bradrick S. S., Pompon Julien, Garcia-Blanco M. A.
Source
RNA Biology, 2020,
17 (3), 366-380 ISSN 1547-6286
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 IFN beta 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 IFN beta activation and knockout of MAVS in the QKI knockout cells completely abolishes IFN beta induction. Consistently, ectopic expression of RIG-I activates stronger IFN beta 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.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Entomologie médicale / Parasitologie / Virologie [052]
