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- Title
IL-17 integrates multiple self-reinforcing, feed-forward mechanisms through the RNA binding protein Arid5a.
- Authors
Amatya, Nilesh; Childs, Erin E.; Cruz, J. Agustin; Aggor, Felix E. Y.; Garg, Abhishek V.; Berman, Andrea J.; Gudjonsson, Johann E.; Atasoy, Ulus; Gaffen, Sarah L.
- Abstract
Interleukin-17A (IL-17A) not only stimulates immunity to fungal pathogens but also contributes to autoimmune pathology. IL-17 is only a modest activator of transcription in experimental tissue culture settings. However, IL-17 controls posttranscriptional events that enhance the expression of target mRNAs. Here, we showed that the RNA binding protein (RBP) Arid5a (AT-rich interactive domain-containing protein 5a) integrated multiple IL-17-driven signaling pathways through posttranscriptional control of mRNA. IL-17 induced expression of Arid5a, which was recruited to the adaptor TRAF2. Arid5a stabilized IL-17-induced cytokine transcripts by binding to their 3' untranslated regions and also counteracted mRNA degradation mediated by the endoribonuclease MCPIP1 (Regnase-1). Arid5a inducibly associated with the eukaryotic translation initiation complex and facilitated the translation of the transcription factors (TFs) IκkBζ (Nfkbiz) and C/EBPβ (Cebpb). These TFs in turn transactivated IL-17-dependent promoters. Together, these data indicated that Arid5a orchestrates a feed-forward amplification loop, which promoted IL-17 signaling by controlling mRNA stability and translation.
- Subjects
INTERLEUKIN-17; INTERLEUKINS; AUTOIMMUNE disease prevention; ENDORIBONUCLEASES; TRANSCRIPTION factors; THERAPEUTICS
- Publication
Science Signaling, 2018, Vol 11, Issue 551, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.aat4617