HuR is required for IL-17–induced Act1-mediated CXCL1 and CXCL5 mRNA stabilization

T Herjan, P Yao, W Qian, X Li, C Liu… - The Journal of …, 2013 - journals.aai.org
T Herjan, P Yao, W Qian, X Li, C Liu, K Bulek, D Sun, WP Yang, J Zhu, A He, JA Carman…
The Journal of Immunology, 2013journals.aai.org
IL-17, a major inflammatory cytokine plays a critical role in the pathogenesis of many
autoimmune inflammatory diseases. In this study, we report a new function of RNA-binding
protein HuR in IL-17–induced Act1-mediated chemokine mRNA stabilization. HuR
deficiency markedly reduced IL-17–induced chemokine expression due to increased mRNA
decay. Act1-mediated HuR polyubiquitination was required for the binding of HuR to CXCL1
mRNA, leading to mRNA stabilization. Although IL-17 induced the coshift of Act1 and HuR to …
Abstract
IL-17, a major inflammatory cytokine plays a critical role in the pathogenesis of many autoimmune inflammatory diseases. In this study, we report a new function of RNA-binding protein HuR in IL-17–induced Act1-mediated chemokine mRNA stabilization. HuR deficiency markedly reduced IL-17–induced chemokine expression due to increased mRNA decay. Act1-mediated HuR polyubiquitination was required for the binding of HuR to CXCL1 mRNA, leading to mRNA stabilization. Although IL-17 induced the coshift of Act1 and HuR to the polysomal fractions in a sucrose gradient, HuR deficiency reduced the ratio of translation-active/translation-inactive IL-17–induced chemokine mRNAs. Furthermore, HuR deletion in distal lung epithelium attenuated IL-17–induced neutrophilia. In summary, HuR functions to couple receptor-proximal signaling to posttranscriptional machinery, contributing to IL-17–induced inflammation.
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