Open AccessCIKS/DDX3X Interaction Controls the Stability of the Zc3h12a mRNA Induced by IL-17
Author(s) -
Domenico Somma,
Paola Mastrovito,
Michèle Grieco,
Alfonso Lavorgna,
Angelica Pignalosa,
Luigi Formisano,
Anna Maria Salzano,
Andrea Scaloni,
Francesco Pacifico,
Ulrich Siebenlist,
Antonio Leonardi
Publication year - 2015
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.1401589
Subject(s) - gene knockdown , proinflammatory cytokine , messenger rna , rna helicase a , signal transducing adaptor protein , microbiology and biotechnology , transcription factor , dead box , biology , helicase , signal transduction , gene , rna , inflammation , immunology , genetics
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.
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