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This article is part of the supplement: Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

Open Badges Oral presentation

The role of mRNA degradation in immunity and inflammation

Shizuo Akira

Author affiliations

Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita City, Osaka 565-0871, Japan

Citation and License

Arthritis Research & Therapy 2012, 14(Suppl 1):O7  doi:10.1186/ar3562

The electronic version of this article is the complete one and can be found online at:

Published:9 February 2012

© 2012 Akira; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oral presentation

The innate immune system is an evolutionally conserved host defense mechanism against pathogens. Innate immune responses are initiated by pattern recognition receptors (PRRs), which recognize specific structures of microorganisms. Among them, Toll-like receptors (TLRs) are capable of sensing organisms ranging from bacteria to fungi, protozoa and viruses, and play a major role in innate immunity. Individual TLRs recognize different microbial components, and give rise to different patterns in gene expression.

We are now focusing on the role of genes induced in response to TLR stimulation, particularly the genes that are rapidly induced in a MyD88-dependent manner within 30 min after LPS stimulation. Among them, we have recently identified a novel gene named Zc3h12a which has a CCCH-type zinc finger domain. The knockout mice developed spontaneous autoimmune diseases accompanied by splenomegaly and lymphadenopathy. Subsequent studies showed that Zc3h12a is a nuclease involved in destabilization of IL-6 and IL-12mRNA. We renamed it Regulatory RNase-1 (Regnase-1) based on the function.

We recently found that the IKK complex controls Il6 mRNA stability by phosphorylating Regnase-1 in response to IL-1R/TLR stimulation. Phosphorylated Regnase-1 underwent ubiquitination and degradation. Regnase-1 re-expressed in IL-1R/TLR-activated cells exhibited delayed kinetics, and Regnase-1 mRNA was found to be negatively regulated by Regnase-1 itself via a stem-loop region present in the Regnase-1 3' untranslated region. These data demonstrate that the IKK complex phosphorylates not only IkBalpha, activating transcription, but also Regnase-1, releasing the "brake" on Il6 mRNA expression.