Carbamoyl-phosphate synthase 1 regulatory RNA (CPS1 regRNA)

The Carbamoyl-phosphate synthase 1 regulatory RNA (CPS1 regRNA) is a non-coding RNA molecule that functions as a localized controller of the transcription of the CPS1 gene [5, 6]. CPS1 is the rate-limiting enzyme of the urea cycle, primarily expressed in the liver, where it catalyzes the first step of ammonia detoxification by converting ammonia and bicarbonate into carbamoyl phosphate [3, 6]. The regRNA acts as a master regulator at the CPS1 locus, modulating the activity of transcription factors and RNA polymerase to determine the levels of CPS1 mRNA produced [5, 11]. This target is the focus of novel therapeutic strategies, such as the antisense oligonucleotide CMP-CPS-001, which is designed to bind the regRNA and upregulate endogenous CPS1 expression [5, 12]. By increasing the production of functional CPS1 protein, these therapies aim to treat urea cycle disorders (UCDs) by enhancing the body's capacity to clear toxic ammonia [6, 12]. This approach represents a potential disease-modifying treatment for patients with partial CPS1 deficiency or other UCDs where protein amplification is beneficial [5, 6].

Other names

CPS1-specific regulatory RNACPS1 regRNACPS1 regulatory RNACPS1-specific regRNACarbamoyl-phosphate synthase 1 intronic transcript 1 (CPS1-IT1)

Antisense oligonucleotide-mediated upregulation of CPS1 gene expression by binding to a specific regulatory RNA sequence to increase mRNA transcription [5, 6].