Regnase-1, a key endoribonuclease responsible for the inflammatory and immune responses
Speaker: Shizuo Akira
Laboratory of Host Defense, WPI Immunology Frontier Research Center, and Department of Host Defense, Research Institute for Microbial Diseases, University of Osaka [Osaka, Japan]
Host: Pedro A. Lazo-Zbikowski
Salón de actos del Centro de Investigación del Cáncer
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. We have shown that Regnase-1 encoded by the Zc3h12a gene is an endoribonuclease involved in destabilization of a variety of mRNAs including IL-6，IL-12, and Regnase-1 itself mRNAs via the stem loop structure present in the 3’UTR of these mRNAs. Although originally identified as the LPS-inducible gene, Regnase-1 protein is present in unstimulated cells, and disappears in response to Toll-like receptor ligands via an IKK-dependent proteasome degradation pathway or in response to T cell receptor stimulation through the cleavage by Malt-1. Thus, Regnase-1 acts as a brake in unstimulated cells as well as a negative feedback regulator after cellular activation. Recently we found that IL-17 signal also inhibits the function of Regnase-1. Regnase-1 is detached from the ER via Act-1 dependent TBK1/IKKi phosphorylation, which shuts down its ability to destabilize target mRNAs. I would like to discuss the role of Regnase-1 in the inflammatory and immune responses.