Zinc finger CCCH domain-containing protein 12A messenger RNA (ZC3H12A mRNA)

Zinc finger CCCH domain-containing protein 12A (ZC3H12A) messenger RNA encodes the protein Regnase-1 (also known as MCPIP1), a critical endoribonuclease that maintains immune homeostasis by degrading pro-inflammatory mRNAs [1][2]. Regnase-1 recognizes specific stem-loop structures in the 3' untranslated regions (UTRs) of target transcripts, such as Interleukin-6 and Interleukin-12b, thereby preventing excessive immune activation and preventing autoimmunity [2][4]. In therapeutic contexts, ZC3H12A mRNA is targeted for modulation to either dampen hyper-inflammation or enhance anti-tumor immunity. For instance, delivering ZC3H12A mRNA via lipid nanoparticles is being explored as a strategy to treat autoimmune disorders and cytokine storms by restoring post-transcriptional control over cytokine production [2][5]. Conversely, the depletion of ZC3H12A mRNA in adoptive cell therapies, such as CAR-T cells, has been shown to improve metabolic fitness and anti-tumor efficacy by removing a key negative regulator of T-cell activation and persistence [3]. Thus, ZC3H12A mRNA serves as a sophisticated molecular switch for controlling the duration and intensity of the inflammatory response, making it a high-interest target for both immunology and oncology [1][3]. References: [1] UniProt (Q5D1E8); [2] Matsushita et al. (2009) Nature 459:1106-1110; [3] Wei et al. (2019) Nature 576:471-476; [4] Mino et al. (2015) Cell 161:1058-1073; [5] Fu and Blackshear (2017) Nat Rev Immunol 17:490-501.

Other names

Regnase-1 mRNAMCPIP1 mRNAZinc finger CCCH-type containing 12A mRNAMonocyte chemotactic protein-induced protein 1 mRNA

mRNA augmentation or RNA interference