CIKS/DDX3X interaction controls the stability of the Zc3h12a mRNA induced by IL-17

• Published in: The Journal of immunology (1950) 2015-04, Vol.194 (7), p.3286-3294
• Main Authors: Somma, Domenico, Mastrovito, Paola, Grieco, Marianeve, Lavorgna, Alfonso, Pignalosa, Angelica, Formisano, Luigi, Salzano, Anna Maria, Scaloni, Andrea, Pacifico, Francesco, Siebenlist, Ulrich, Leonardi, Antonio
• Format: Article
• Language: English
• Subjects: DEAD-box RNA Helicases - metabolism; Gene Expression Regulation - drug effects; Humans; I-kappa B Kinase - metabolism; Interleukin-17 - metabolism; Interleukin-17 - pharmacology; Multiprotein Complexes - metabolism; Protein Binding - drug effects; Ribonucleases - genetics; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; TNF Receptor-Associated Factor 2 - metabolism; TNF Receptor-Associated Factor 5 - metabolism; Transcription Factors - genetics; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401589

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.