Serpin family H member 1 messenger RNA 3'-untranslated region (SERPINH1 mRNA 3'-UTR)

The Serpin family H member 1 (SERPINH1) messenger RNA 3'-untranslated region (3'-UTR) is a critical regulatory segment of the mRNA that encodes the protein HSP47, a collagen-specific molecular chaperone. HSP47 is essential for the proper folding, stabilization, and intracellular transport of procollagen molecules within the endoplasmic reticulum (UniProt P50454). In various fibrotic conditions, the overexpression of SERPINH1 leads to the excessive production and deposition of collagen, which results in tissue scarring and organ failure (PubMed 28811298). The 3'-UTR of this mRNA is a strategic target for RNA interference (RNAi) therapies, such as small interfering RNAs (siRNAs), which bind to the sequence to trigger mRNA degradation and subsequent reduction in HSP47 protein synthesis. One prominent therapeutic candidate, BMS-986263 (formerly ND-L02-s0201), utilizes this mechanism to treat advanced liver fibrosis and pulmonary fibrosis by specifically knocking down HSP47 in collagen-producing cells like hepatic stellate cells (ClinicalTrials.gov NCT02220855). By targeting the mRNA rather than the protein, these therapies can effectively halt the fibrotic process at its source, offering a potential disease-modifying approach for chronic fibroproliferative disorders.

Other names

HSP47 mRNA 3'-UTRHeat shock protein 47 mRNA 3'-UTRColligin-1 mRNA 3'-UTRCBP1 mRNA 3'-UTRSERPINH1 3'-untranslated region

RNA interference (RNAi) mediated mRNA degradation leading to reduced HSP47 protein expression