PMID- 23676272 OWN - NLM STAT- MEDLINE DCOM- 20130806 LR - 20211021 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 110 IP - 23 DP - 2013 Jun 4 TI - Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo. PG - 9409-14 LID - 10.1073/pnas.1307419110 [doi] AB - 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-alpha mRNA through binding to the 3' untranslated region of IL-6 mRNA. Arid5a was enhanced in macrophages in response to LPS, IL-1beta, 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. FAU - Masuda, Kazuya AU - Masuda K AD - Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. FAU - Ripley, Barry AU - Ripley B FAU - Nishimura, Riko AU - Nishimura R FAU - Mino, Takashi AU - Mino T FAU - Takeuchi, Osamu AU - Takeuchi O FAU - Shioi, Go AU - Shioi G FAU - Kiyonari, Hiroshi AU - Kiyonari H FAU - Kishimoto, Tadamitsu AU - Kishimoto T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130515 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (3' Untranslated Regions) RN - 0 (Arid5a protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (RNA-Binding Proteins) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - EC 1.13.12.- (Luciferases) RN - EC 3.1.- (Ribonucleases) RN - EC 3.1.- (Zc3h12a protein, mouse) SB - IM MH - 3' Untranslated Regions/genetics MH - Animals MH - Cell Culture Techniques MH - DNA-Binding Proteins/*immunology/metabolism MH - Encephalomyelitis, Autoimmune, Experimental/*immunology MH - Enzyme-Linked Immunosorbent Assay MH - Interleukin-6/blood/*immunology MH - Lipopolysaccharides MH - Luciferases MH - Macrophages/metabolism MH - Mice MH - Mice, Inbred C57BL MH - RNA Stability/*immunology MH - RNA-Binding Proteins/*immunology/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Ribonucleases/antagonists & inhibitors MH - Transcription Factors/*immunology/metabolism MH - Transfection MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC3677444 OTO - NOTNLM OT - RNA-protein complex OT - immune regulation COIS- The authors declare no conflict of interest. EDAT- 2013/05/17 06:00 MHDA- 2013/08/07 06:00 PMCR- 2013/12/04 CRDT- 2013/05/17 06:00 PHST- 2013/05/17 06:00 [entrez] PHST- 2013/05/17 06:00 [pubmed] PHST- 2013/08/07 06:00 [medline] PHST- 2013/12/04 00:00 [pmc-release] AID - 1307419110 [pii] AID - 201307419 [pii] AID - 10.1073/pnas.1307419110 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9409-14. doi: 10.1073/pnas.1307419110. Epub 2013 May 15.