1. CIKS/DDX3X Interaction Controls the Stability of the Zc3h12a mRNA Induced by IL-17
- Author
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Anna Maria Salzano, Antonio Leonardi, Paola Mastrovito, Francesco Pacifico, Angelica Pignalosa, Andrea Scaloni, Luigi Formisano, Ulrich Siebenlist, Domenico Somma, Alfonso Lavorgna, Marianeve Grieco, Somma, Domenico, Mastrovito, P., Grieco, M., Lavorgna, A., Pignalosa, A., Formisano, L., Salzano, A. M., Scaloni, A., Pacifico, F., Siebenlist, U., and Leonardi, Antonio
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Chemokine ,DEAD box ,RNA Stability ,Immunology ,Stimulation ,Article ,Proinflammatory cytokine ,DEAD-box RNA Helicases ,Ribonucleases ,Humans ,Immunology and Allergy ,RNA, Messenger ,Adaptor Proteins, Signal Transducing ,TNF Receptor-Associated Factor 5 ,Gene knockdown ,Messenger RNA ,biology ,Interleukin-17 ,RNA ,Signal transducing adaptor protein ,TNF Receptor-Associated Factor 2 ,Molecular biology ,Tumor Necrosis Factor Receptor-Associated Peptides and Proteins ,I-kappa B Kinase ,Cell biology ,Gene Expression Regulation ,Multiprotein Complexes ,biology.protein ,Protein Binding ,Transcription Factors - Abstract
IL-17 is a proinflammatory cytokine that promotes the expression of different cytokines and chemokines via the induction of gene transcription and the posttranscriptional stabilization of mRNAs. In this study, we show that IL-17 increases the half-life of the Zc3h12a mRNA via interaction of the adaptor protein CIKS with the DEAD box protein DDX3X. IL-17 stimulation promotes the formation of a complex between CIKS and DDX3X, and this interaction requires the helicase domain of DDX3X but not its ATPase activity. DDX3X knockdown decreases the IL-17–induced stability of Zc3h12a without affecting the stability of other mRNAs. IKKε, TNFR-associated factor 2, and TNFR-associated factor 5 were also required to mediate the IL-17–induced Zc3h12a stabilization. DDX3X directly binds the Zc3h12a mRNA after IL-17 stimulation. Collectively, our findings define a novel, IL-17–dependent mechanism regulating the stabilization of a selected mRNA.
- Published
- 2015
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