Jagged-1 mRNA 3' untranslated region (JAG1 mRNA 3'UTR) (JAG1 mRNA 3'UTR)

Jagged-1 (JAG1) is a transmembrane protein that serves as a primary ligand for the Notch signaling pathway, which is essential for cell fate determination, proliferation, and differentiation (UniProt P78504). The 3' untranslated region (3'UTR) of the JAG1 mRNA is a critical regulatory domain containing binding sites for microRNAs (miRNAs) and RNA-binding proteins that modulate the stability and translation of the transcript (PubMed: 20505020). Dysregulation of JAG1, often mediated by loss of 3'UTR-dependent control, is a hallmark of several malignancies, including breast, liver, and colorectal cancers, where it drives epithelial-mesenchymal transition (EMT) and metastasis (PubMed: 23603116). In addition to oncology, mutations or regulatory defects in JAG1 are linked to Alagille syndrome, a multisystem disorder affecting the liver and heart (NIH: Genetic Home Reference). Therapeutic targeting of the JAG1 mRNA 3'UTR using miRNA mimics or antisense oligonucleotides (ASOs) aims to downregulate JAG1 protein levels by promoting mRNA degradation or blocking translation. This RNA-targeted approach provides a mechanism to specifically inhibit JAG1-mediated Notch activation, potentially offering a more targeted safety profile than pan-Notch inhibitors. Experimental studies have demonstrated that restoring miRNAs like miR-199a or miR-26a can effectively suppress JAG1 expression and inhibit tumor progression in preclinical models (PubMed: 25633545).

Other names

JAG1 3'-UTRJagged1 3' untranslated regionJAG1 3'UTR

Targeting of the 3' untranslated region to induce mRNA degradation or translational repression, thereby reducing Jagged-1 protein expression and downstream Notch signaling.