Polycystic kidney disease 1 3' untranslated region (PKD1 3' UTR)

The Polycystic kidney disease 1 (PKD1) 3' untranslated region (UTR) is a key regulatory segment of the PKD1 messenger RNA that modulates the expression of the Polycystin-1 (PC1) protein. In Autosomal Dominant Polycystic Kidney Disease (ADPKD), the level of PC1 often falls below a critical threshold due to mutations, leading to the formation of progressive fluid-filled cysts in the kidneys [1][6]. This 3' UTR region contains conserved binding motifs for microRNAs, particularly the miR-17 family, which bind to the mRNA to inhibit its translation and reduce its stability, thereby further depressing PC1 levels [2][8]. Therapeutic strategies target this region to "de-repress" the remaining functional PKD1 allele, aiming to restore PC1 protein levels to a range that prevents or arrests cyst growth [3][7]. Investigational drugs such as farabursen (RGLS4326) and RGLS8429 act by preventing microRNA-mediated suppression at this site, while experimental steric-blocking oligonucleotides (SBOs) directly occlude the binding motifs [5][8]. By stabilizing PKD1 mRNA and boosting protein production, these approaches offer a potential mutation-agnostic treatment for ADPKD patients [12][21].

Other names

Pkd1 3'-UTRPolycystin-1 3' untranslated regionmiR-17 binding element in PKD1MBE in PKD1PKD1 cis-inhibitory element

Prevention of microRNA binding (specifically miR-17) to the 3' UTR of PKD1 mRNA to de-repress protein translation and increase Polycystin-1 levels.