3'-untranslated region microRNA response element (3'-UTR MRE)

3'-untranslated region microRNA response elements (3'-UTR MREs) are specific nucleotide sequences located within the 3' untranslated region of messenger RNA (mRNA) that are recognized and bound by microRNAs (miRNAs). These elements are fundamental to post-transcriptional gene regulation, as the binding of a miRNA-induced silencing complex (miRISC) to an MRE typically leads to the degradation of the mRNA transcript or the inhibition of its translation into protein (Bartel, 2009, Cell). In various pathologies, including cancer and cardiovascular diseases, mutations within these MREs or changes in miRNA availability can lead to the escape of oncogenes from regulation or the inappropriate silencing of tumor suppressors (Ryan et al., 2010, Nature Reviews Cancer). Therapeutic strategies targeting MREs include the use of antisense oligonucleotides (ASOs) known as target site blockers (TSBs), which physically occupy the MRE to prevent miRNA binding and thereby restore protein expression (Baumann and Winkler, 2014, Frontiers in Bioengineering and Biotechnology). Additionally, miRNA mimics can be introduced to target these elements when endogenous miRNA levels are insufficient. The specificity of the MRE-miRNA interaction makes these sites attractive targets for precision medicine, although challenges remain regarding the delivery of nucleic acid therapeutics and potential off-target effects on other mRNAs containing similar sequences.

Other names

miRNA binding siteMicroRNA response elementMRE3'-UTR regulatory elementSeed match site

Targeting 3'-UTR MREs involves either the use of miRNA mimics to enhance the natural repressive effect on a target mRNA or the use of antisense oligonucleotides (ASOs), such as target site blockers (TSBs), to sterically hinder the binding of endogenous miRNAs, thereby preventing gene silencing and increasing protein production.