Messenger RNA 3'-untranslated region (3'-UTR)

The messenger RNA 3'-untranslated region (3'-UTR) is the section of a mature mRNA molecule that follows the translation termination codon and precedes the poly(A) tail. It plays a fundamental role in post-transcriptional gene regulation by harboring binding sites for microRNAs (miRNAs) and RNA-binding proteins (RBPs) that control mRNA stability, intracellular localization, and translation efficiency (Mayr, 2019, Cold Spring Harb Perspect Biol). Dysregulation of 3'-UTR-mediated control, often through mutations or alternative polyadenylation, is implicated in various pathologies, including cancer, where it can lead to the stabilization of oncogenic transcripts (Conne et al., 2000, Nature Medicine). As a therapeutic target, the 3'-UTR is highly valuable for RNA-based medicines such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), which can be designed to bind with high specificity to trigger transcript degradation or modulate protein production. For example, the siRNA drug Patisiran and the ASO Inotersen both target the 3'-UTR of the transthyretin (TTR) mRNA to reduce the production of amyloidogenic proteins in patients with hereditary transthyretin-mediated amyloidosis (Adams et al., 2018, N Engl J Med). This targeting strategy allows for the precise knockdown of disease-causing proteins without modifying the genomic DNA or the protein-coding sequence itself.

Other names

3' untranslated region3' trailermRNA 3'-UTRThree prime untranslated region

Drugs targeting the 3'-UTR typically function through RNA interference (RNAi) to induce transcript degradation, recruitment of RNase H for cleavage, or steric hindrance to block microRNA binding and regulatory protein interactions.