Regnase-1, a ribonuclease involved in the inflammatory and immune responses

Regnase-1, a ribonuclease involved in the inflammatory and immune responses

Regnase-1, a ribonuclease involved in the inflammatory and immune responses (#S-1)

Shizuo Akira ¹

Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan

Gene expression is controlled at multiple points, including signal transduction, transcription and mRNA stability. So far, transcriptional regulation has been extensively studied. However, recent studies have revealed that control of gene expression at the mRNA level is as important as transcriptional control in the immune response.

The innate immune system is an evolutionally conserved host defense mechanism against pathogens. Innate immune responses are initiated by activation of pattern recognition receptors (PRRs), which recognize microbial components. 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, activate different signaling pathways via selective usage of adaptor molecules, 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 via the stem loop structure present in the 3’UTR of these genes. We renamed it Regulatory RNase-1 (Regnase-1) based on the function. I would like to discuss the role of Regnase-1 in the immune response.

Authors contributing to this presentation.

Akira, S

Shizuo Akira is a director and professor of WPI Immunology Frontier Research Center, and also a professor in Institute for Microbial Diseases at Osaka University, Japan. He received his M.D. and Ph.D. from Osaka University. After two years of postdoctoral working in Department of Immunology, University of California at Berkeley, he started to study on IL-6 gene regulation and signaling in the Institute for Molecular and Cellular Biology, Osaka University, and cloned transcription factors, NF-IL6(C/EBP beta) and STAT3. He was a professor in Department of Biochemistry, Hyogo College of Medicine from 1996 to 1999, where he became involved in Toll-like receptors research. By generating TLR family knockout mice, he identified ligands of many TLR members. He also demonstrated that the difference in signaling pathway among TLRs is due to selective usage of adaptor molecules such as MyD88 and TRIF. He demonstrated that pathogen-derived RNA is recognized by cytoplasmic receptor family, besides TLRs, and clarified the molecular mechanism of antiviral response against RNA viruses. His current research interests are molecular mechanisms of innate immunity and inflammation, which are studied mainly by generating knockout mice. Awards and Honors: 2004 Robert Koch Prize (Robert Koch Foundation, Germany), 2006 William B. Coley Award for Distinguished Research in Basic Immunology (Cancer Research Institute, USA), 2007 Imperial Prize and Japan Academy Prize (Japan Academy), 2009 National Academy of Sciences of USA, Foreign Associate, 2009 Person of Cultural Merit (Japanese Government), 2010 Keio International Medical Science Prize (Keio University), 2010 Avery-Landsteiner Prize (German Society for Immunology), 2010 EMBO Associate Member

Regnase-1, a ribonuclease involved in the inflammatory and immune responses (#S-1)

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Akira, S

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