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

Interleukin 17 (IL-17) promotes the expression of cytokines and proteins involved in inflammation response via the induction of gene transcription and post-transcriptional stabilization of mRNA. We show here that IL-17 enhanced the stability of zc3h12a mRNA through the RNA binding protein DDX3X. After receptor triggering DDX3X binds the ubiquitin ligase CIKS trough the helicase domain and stabilize zc3h12a mRNA by directly binding the mRNA. This process involved CIKS (but the E3 ubiquitin ligase function is dispensable) the adaptors TRAF2 and TRAF5, and the kinase IKK?. Zc3h12a is an endonuclease involved in controlling inflammatory responses by degrading mRNA of some inflammatory protein such as IL-6. This effect is important to correctly switch-off the IL-17-dependent inflammation.