Messenger RNA 3' untranslated regions (3'UTR)

The messenger RNA 3' untranslated region (3'UTR) is the section of an mRNA molecule that follows the translation termination codon and precedes the poly(A) tail. These regions serve as critical hubs for post-transcriptional regulation, containing various cis-regulatory elements such as AU-rich elements (AREs) and binding sites for microRNAs (miRNAs) and RNA-binding proteins (RBPs) (Mayr, 2017). Through these interactions, 3'UTRs govern the stability, subcellular localization, and translation efficiency of the transcript (Barrett et al., 2012). Dysregulation of 3'UTR-mediated control, often through mutations or alternative polyadenylation, is implicated in numerous diseases, including cancer, where shortened 3'UTRs can lead to the overexpression of oncogenes by escaping miRNA-mediated repression (Passacantilli et al., 2017). In therapeutic development, 3'UTRs are targeted by antisense oligonucleotides (ASOs) and siRNAs to modulate protein production or induce transcript degradation, and they are increasingly explored as targets for small molecules designed to interfere with specific RNA-protein interactions (Crooke et al., 2021).

Other names

3'-untranslated region3'-UTRTrailer sequencemRNA 3'UTR3' untranslated region

Drugs targeting mRNA 3'UTRs typically function by binding to specific regulatory sequences to either promote RNA degradation (via RNase H or RNAi pathways) or to sterically hinder the binding of microRNAs and RNA-binding proteins, thereby modulating the stability and translation of the target message (Crooke et al., 2021).