Skip to main content
  • Oral presentation
  • Open access
  • Published:

The role of mRNA degradation in immunity and inflammation

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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Shizuo Akira.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article

Akira, S. The role of mRNA degradation in immunity and inflammation. Arthritis Res Ther 14 (Suppl 1), O7 (2012).

Download citation

  • Published:

  • DOI: