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Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9409-14. doi: 10.1073/pnas.1307419110. Epub 2013 May 15.

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

Author information

1
Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.

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

PMID:
23676272
PMCID:
PMC3677444
DOI:
10.1073/pnas.1307419110
[Indexed for MEDLINE]
Free PMC Article

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