Adenylate-Uridylate-rich element-containing messenger RNA (ARE-mRNA) (ARE-mRNA)

Adenylate-Uridylate-rich element-containing messenger RNAs (ARE-mRNAs) are a class of transcripts characterized by specific AU-rich motifs, most commonly the AUUUA pentamer, located within their 3' untranslated regions (3'UTRs) (Khabar, 2017). These elements serve as critical post-transcriptional regulatory signals that dictate the stability and translational efficiency of the mRNA by recruiting various AU-rich element-binding proteins (ARE-BPs) (Garcia-Maurino et al., 2017). In healthy cells, AREs ensure the rapid turnover of potent signaling molecules such as cytokines (e.g., TNF-alpha, IL-6) and proto-oncogenes (e.g., MYC, FOS), allowing for transient and tightly controlled gene expression (Bakheet et al., 2018). Dysregulation of the ARE-mediated pathway, often through the overexpression of stabilizing proteins like HuR (ELAVL1) or the loss of destabilizing proteins like Tristetraprolin (TTP/ZFP36), leads to the pathological stabilization of these mRNAs, contributing to chronic inflammation and oncogenesis (Wu et al., 2019). Therapeutic strategies targeting ARE-mRNAs primarily focus on small molecules that disrupt the interaction between AREs and stabilizing RBPs or antisense oligonucleotides designed to modulate the decay of specific ARE-containing transcripts (Muralidharan et al., 2017). Because AREs are present in approximately 5-10% of all human genes, targeting this pathway offers a broad therapeutic window for treating diverse pathologies but also presents significant challenges regarding specificity and potential off-target effects (Khabar, 2017). Small molecule inhibitors like MS-444 and CMLD-2 have demonstrated efficacy in preclinical models by preventing the stabilization of oncogenic ARE-mRNAs by HuR (Meisner et al., 2007). Overall, ARE-mRNAs represent a pivotal node in gene regulation that is increasingly being explored for its potential in precision medicine and RNA-targeted drug discovery.

Other names

AU-rich element-containing mRNAARE-containing mRNAAU-rich elementARE-mRNA3'UTR AU-rich element

Inhibition of RNA-binding protein (RBP) recruitment to AU-rich elements, leading to increased mRNA decay or decreased translation.