title: Regnase-1, a ribonuclease involved in the regulation of immune responses.
abstract: Zc3h12a is a lipopolysaccharide-inducible gene and has a CCCH-type zinc-finger domain. Zc3h12a knockout mice develop spontaneous autoimmune diseases accompanied by splenomegaly and by lymphadenopathy. Subsequent studies show that Zc3h12a is a nuclease involved in destabilization of interleukin (IL)-6 and IL-12 mRNA via the stem loop structure within the 3' UTR of these genes. Thus, we renamed it regulatory RNase-1 (Regnase-1) based on its function. IκB kinases phosphorylate and degrade Regnase-1 protein in macrophages in response to IL-1R/Toll-like receptor (TLR) stimulation. T-cell-specific deletion of Regnase-1 produces pathogenic T cells with hyperactivated phenotypes as well as autoimmune diseases. Regnase-1 protein is cleaved by Malt1 and inactivated in response to T-cell receptor stimulation. Thus, Regnase-1 is a key molecule in the regulation of immune responses.
authors.affiliation: Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan sakira@biken.osaka-u.ac.jp.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007107:Immune System; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D015850:Interleukin-6; D008024:Ligands; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D014157:Transcription Factors; D018664:Interleukin-12; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C541320:Zc3h12a protein, mouse