Zinc finger CCCH domain-containing protein 12A (Regnase-1) (ZC3H12A)

Regnase-1, encoded by the ZC3H12A gene, is a critical endoribonuclease that regulates immune homeostasis by degrading mRNAs of various pro-inflammatory cytokines and transcription factors (UniProt Q5D1E8). It acts as a "brake" on the immune system, preventing excessive inflammation by targeting transcripts like IL-6 and IL-12b for degradation through its PIN domain (Matsushita et al., 2009, Nature). In the context of oncology, the Regnase-1 gene locus has emerged as a high-priority target for genetic modification in adoptive cell therapies, such as CAR-T cells. Deleting or knocking out Regnase-1 in T cells prevents the degradation of key effector mRNAs, leading to enhanced T-cell expansion, improved metabolic fitness, and sustained anti-tumor activity even in the immunosuppressive tumor microenvironment (Wei et al., 2019, Nature; Jing et al., 2022, Cell Reports). However, because Regnase-1 is essential for preventing autoimmunity, therapeutic strategies must carefully balance enhanced immune potency with the risk of systemic inflammatory toxicities (Uehata et al., 2013, Cell).

Other names

Regnase-1MCPIP1Monocyte chemotactic protein-induced protein 1ZC3H12A

Genetic knockout of the Regnase-1 gene locus to stabilize effector mRNAs and enhance T-cell anti-tumor activity.