title: CIKS/DDX3X interaction controls the stability of the Zc3h12a mRNA induced by IL-17.
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.
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, 80131 Naples, Italy;
authors.forename: Domenico
authors.initials: D
authors.lastname: Somma
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, 80131 Naples, Italy;
authors.forename: Paola
authors.initials: P
authors.lastname: Mastrovito
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, 80131 Naples, Italy;
authors.forename: Marianeve
authors.initials: M
authors.lastname: Grieco
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, 80131 Naples, Italy;
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lavorgna
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, 80131 Naples, Italy;
authors.forename: Angelica
authors.initials: A
authors.lastname: Pignalosa
authors.affiliation: Dipartimento di Neuroscienze, Università Federico II di Napoli, 80131 Naples, Italy;
authors.forename: Luigi
authors.initials: L
authors.lastname: Formisano
authors.affiliation: Laboratorio di Proteomica e Spettrometria di Massa, Istituto per il Sistema Produzione Animale in Ambiente Mediterraneo, Consiglio Nazionale delle Ricerche, 80147 Naples, Italy;
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Salzano
authors.affiliation: Laboratorio di Proteomica e Spettrometria di Massa, Istituto per il Sistema Produzione Animale in Ambiente Mediterraneo, Consiglio Nazionale delle Ricerche, 80147 Naples, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.affiliation: Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy; and.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pacifico
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Siebenlist
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, 80131 Naples, Italy; leonardi@unina.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Leonardi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism* / Q000494:pharmacology; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics*; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D048015:TNF Receptor-Associated Factor 5 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020381:Interleukin-17; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D047992:TNF Receptor-Associated Factor 2; D048015:TNF Receptor-Associated Factor 5; C414202:TRAF3IP2 protein, human; D014157:Transcription Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D051550:I-kappa B Kinase; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases