CIKS/DDX3X Interaction Controls the Stability of the Zc3h12a MRNA Induced by IL-17

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2015 Feb 25

PMID 25710910

Citations 22

Authors

Domenico Somma

Paola Mastrovito

Marianeve Grieco

Alfonso Lavorgna

Angelica Pignalosa

Luigi Formisano

Anna Maria Salzano

Andrea Scaloni

Francesco Pacifico

Ulrich Siebenlist

Antonio Leonardi

Affiliations

Soon will be listed here.

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.

Citing Articles

Interleukin 17A promotes glycolysis to activate human hepatic stellate cells by mediating the TRAF2/TRAF5/HuR/PFKFB3 axis.

Jiang T, Li S, Tang L, Tan Y, Ouyang W Cent Eur J Immunol. 2025; 49(4):404-424.

PMID: 39944257 PMC: 11811719. DOI: 10.5114/ceji.2024.145013.

Modulation of DAPK1 expression by its alternative splice variant DAPK1-215 in cancer.

Wang Q, Weng S, Zhong W, Lin Y, Yu Y, Huang Y J Transl Med. 2025; 23(1):85.

PMID: 39833825 PMC: 11744996. DOI: 10.1186/s12967-025-06127-9.

2'-O-methylation at internal sites on mRNA promotes mRNA stability.

Li Y, Yi Y, Gao X, Wang X, Zhao D, Wang R Mol Cell. 2024; 84(12):2320-2336.e6.

PMID: 38906115 PMC: 11196006. DOI: 10.1016/j.molcel.2024.04.011.

Act1 drives chemoresistance via regulation of antioxidant RNA metabolism and redox homeostasis.

Hong L, Herjan T, Chen X, Zagore L, Bulek K, Wang H J Exp Med. 2024; 221(7).

PMID: 38861022 PMC: 11167376. DOI: 10.1084/jem.20231442.

ZC3H12A inhibits tumor growth and metastasis of breast cancer under hypoxic condition via the inactivation of IL-17 signaling pathway.

Luo Z, Yang F, Liu K, Ding Z Cell Cycle. 2024; 23(2):188-204.

PMID: 38357935 PMC: 11037279. DOI: 10.1080/15384101.2024.2314441.

References

Schroder M . Human DEAD-box protein 3 has multiple functions in gene regulation and cell cycle control and is a prime target for viral manipulation. Biochem Pharmacol. 2009; 79(3):297-306. DOI: 10.1016/j.bcp.2009.08.032. View

Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont M, Ranchin B . Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009; 10(7):778-85. DOI: 10.1038/ni.1741. View

Scippa G, Rocco M, Ialicicco M, Trupiano D, Viscosi V, Di Michele M . The proteome of lentil (Lens culinaris Medik.) seeds: discriminating between landraces. Electrophoresis. 2010; 31(3):497-506. DOI: 10.1002/elps.200900459. View

Kolls J . Th17 cells in mucosal immunity and tissue inflammation. Semin Immunopathol. 2010; 32(1):1-2. PMC: 3424504. DOI: 10.1007/s00281-010-0198-8. View

Oshiumi H, Sakai K, Matsumoto M, Seya T . DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-beta-inducing potential. Eur J Immunol. 2010; 40(4):940-8. DOI: 10.1002/eji.200940203. View

Liang J, Saad Y, Lei T, Wang J, Qi D, Yang Q . MCP-induced protein 1 deubiquitinates TRAF proteins and negatively regulates JNK and NF-kappaB signaling. J Exp Med. 2010; 207(13):2959-73. PMC: 3005225. DOI: 10.1084/jem.20092641. View

Jankowsky E . RNA helicases at work: binding and rearranging. Trends Biochem Sci. 2010; 36(1):19-29. PMC: 3017212. DOI: 10.1016/j.tibs.2010.07.008. View

Sonder S, Saret S, Tang W, Sturdevant D, Porcella S, Siebenlist U . IL-17-induced NF-kappaB activation via CIKS/Act1: physiologic significance and signaling mechanisms. J Biol Chem. 2011; 286(15):12881-90. PMC: 3075635. DOI: 10.1074/jbc.M110.199547. View

Gaffen S . Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009; 9(8):556-67. PMC: 2821718. DOI: 10.1038/nri2586. View

10.

Chang S, Dong C . Signaling of interleukin-17 family cytokines in immunity and inflammation. Cell Signal. 2010; 23(7):1069-75. PMC: 3078175. DOI: 10.1016/j.cellsig.2010.11.022. View

11.

Linder P, Jankowsky E . From unwinding to clamping - the DEAD box RNA helicase family. Nat Rev Mol Cell Biol. 2011; 12(8):505-16. DOI: 10.1038/nrm3154. View

12.

Bulek K, Liu C, Swaidani S, Wang L, Page R, Gulen M . The inducible kinase IKKi is required for IL-17-dependent signaling associated with neutrophilia and pulmonary inflammation. Nat Immunol. 2011; 12(9):844-52. PMC: 3282992. DOI: 10.1038/ni.2080. View

13.

Sun D, Novotny M, Bulek K, Liu C, Li X, Hamilton T . Treatment with IL-17 prolongs the half-life of chemokine CXCL1 mRNA via the adaptor TRAF5 and the splicing-regulatory factor SF2 (ASF). Nat Immunol. 2011; 12(9):853-60. PMC: 3597344. DOI: 10.1038/ni.2081. View

14.

Iwasaki H, Takeuchi O, Teraguchi S, Matsushita K, Uehata T, Kuniyoshi K . The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. Nat Immunol. 2011; 12(12):1167-75. DOI: 10.1038/ni.2137. View

15.

Sonder S, Paun A, Ha H, Johnson P, Siebenlist U . CIKS/Act1-mediated signaling by IL-17 cytokines in context: implications for how a CIKS gene variant may predispose to psoriasis. J Immunol. 2012; 188(12):5906-14. PMC: 3370149. DOI: 10.4049/jimmunol.1103233. View

16.

Jura J, Skalniak L, Koj A . Monocyte chemotactic protein-1-induced protein-1 (MCPIP1) is a novel multifunctional modulator of inflammatory reactions. Biochim Biophys Acta. 2012; 1823(10):1905-13. DOI: 10.1016/j.bbamcr.2012.06.029. View

17.

Soto-Rifo R, Rubilar P, Limousin T, de Breyne S, Decimo D, Ohlmann T . DEAD-box protein DDX3 associates with eIF4F to promote translation of selected mRNAs. EMBO J. 2012; 31(18):3745-56. PMC: 3442272. DOI: 10.1038/emboj.2012.220. View

18.

Miossec P, Kolls J . Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012; 11(10):763-76. DOI: 10.1038/nrd3794. View

19.

Gu L, Fullam A, Brennan R, Schroder M . Human DEAD box helicase 3 couples IκB kinase ε to interferon regulatory factor 3 activation. Mol Cell Biol. 2013; 33(10):2004-15. PMC: 3647972. DOI: 10.1128/MCB.01603-12. View

20.

Uehata T, Akira S . mRNA degradation by the endoribonuclease Regnase-1/ZC3H12a/MCPIP-1. Biochim Biophys Acta. 2013; 1829(6-7):708-13. DOI: 10.1016/j.bbagrm.2013.03.001. View