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Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo

Masuda, Kazuya, Ripley, Barry, Nishimura, Riko, Mino, Takashi, Takeuchi, Osamu, Shioi, Go, Kiyonari, Hiroshi, Kishimoto, Tadamitsu
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.23 pp. 9409-9414
RNA-binding proteins, autoimmune diseases, autoimmunity, blood serum, encephalitis, interleukin-1beta, interleukin-6, macrophages, messenger RNA, mice, ribonucleases, tumor necrosis factor-alpha
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 H17 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.