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

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-? mRNA through binding to the 3' untranslated region of IL-6 mRNA. Arid5a was enhanced in macrophages in response to LPS, IL-1?, 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.

SUBMITTER: Masuda K

PROVIDER: S-EPMC3677444 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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

Masuda Kazuya K Ripley Barry B Nishimura Riko R Mino Takashi T Takeuchi Osamu O Shioi Go G Kiyonari Hiroshi H Kishimoto Tadamitsu T

Proceedings of the National Academy of Sciences of the United States of America 20130515 23

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 ...[more]

PMID: 23676272

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