Abstract
Posttranscriptional regulation of IL-6 has been largely uncharacterized, with the exception of the ribonuclease Regnase-1, which prevents autoimmunity by destabilizing IL-6 mRNA. Here, we identified AT-rich interactive domain-containing protein 5A (Arid5a) as a unique RNA binding protein, which stabilizes IL-6 but not TNF-α mRNA through binding to the 3' untranslated region of IL-6 mRNA. Arid5a was enhanced in macrophages in response to LPS, IL-1β, and IL-6. Arid5a deficiency inhibited elevation of IL-6 serum level in LPS-treated mice and suppressed IL-6 levels and the development of T(H)17 cells in experimental autoimmune encephalomyelitis. Importantly, Arid5a inhibited the destabilizing effect of Regnase-1 on IL-6 mRNA. These results indicate that Arid5a plays an important role in promotion of inflammatory processes and autoimmune diseases.
Keywords:
RNA-protein complex; immune regulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Animals
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Cell Culture Techniques
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DNA-Binding Proteins / immunology*
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DNA-Binding Proteins / metabolism
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Enzyme-Linked Immunosorbent Assay
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Interleukin-6 / blood
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Interleukin-6 / immunology*
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Lipopolysaccharides
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Luciferases
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Macrophages / metabolism
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Mice
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Mice, Inbred C57BL
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RNA Stability / immunology*
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RNA-Binding Proteins / immunology*
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RNA-Binding Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Ribonucleases / antagonists & inhibitors
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Transcription Factors / immunology*
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Transcription Factors / metabolism
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Transfection
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Tumor Necrosis Factor-alpha / metabolism
Substances
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3' Untranslated Regions
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Arid5a protein, mouse
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DNA-Binding Proteins
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Interleukin-6
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Lipopolysaccharides
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RNA-Binding Proteins
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Transcription Factors
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Tumor Necrosis Factor-alpha
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interleukin-6, mouse
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Luciferases
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Ribonucleases
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Zc3h12a protein, mouse