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

Author:
Masuda, Kazuya, Ripley, Barry, Nishimura, Riko, Mino, Takashi, Takeuchi, Osamu, Shioi, Go, Kiyonari, Hiroshi, Kishimoto, Tadamitsu
Source:
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.23 pp. 9409-9414
ISSN:
0027-8424
Subject:
RNA-binding proteins, autoimmune diseases, autoimmunity, blood serum, encephalitis, interleukin-1beta, interleukin-6, macrophages, messenger RNA, mice, ribonucleases, tumor necrosis factor-alpha
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 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.
Agid:
1736978