Regnase-1, a Ribonuclease Involved in the Regulation of Immune Responses

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.