The RNA binding protein Quaking represses host interferon response by downregulating MAVS.
RNA Biol
; 17(3): 366-380, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-31829086
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(IC) and viral infection-induced IFNß 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 IFNß activation and knockout of MAVS in the QKI knockout cells completely abolishes IFNß induction. Consistently, ectopic expression of RIG-I activates stronger IFNß 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Interferón Tipo I
/
Proteínas de Unión al ARN
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Proteínas Adaptadoras Transductoras de Señales
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Interacciones Huésped-Patógeno
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article