Poly-rich RNA elements (PREs)

Poly-rich RNA elements (PREs) are regulatory sequences found within the 3' untranslated regions (UTRs) of messenger RNAs (mRNAs) that consist of repetitive or enriched sequences of a single nucleotide, most commonly adenosine (A) or uridine (U) (Choi et al., 2020). These elements, which include AU-rich elements (AREs) and GU-rich elements (GREs), serve as critical binding sites for various RNA-binding proteins (RBPs) that control the stability, localization, and translation efficiency of the host mRNA (Garcia-Maurino et al., 2017). In many diseases, such as cancer and chronic inflammation, the dysregulation of PRE-mediated mRNA decay leads to the over-stabilization and overexpression of potent oncogenes and pro-inflammatory cytokines like TNF-alpha and MYC (Choi et al., 2020). Consequently, PREs have emerged as attractive therapeutic targets for small molecules and antisense oligonucleotides (ASOs) designed to either displace pathological RBPs or recruit nucleases to selectively degrade disease-associated transcripts (Disney et al., 2018). Recent advances in RNA-targeted drug discovery, including the development of Ribonuclease Targeting Chimeras (RIBOTACs), have demonstrated the feasibility of modulating gene expression by directly binding to these poly-rich motifs (Choi et al., 2020).

Other names

AU-rich elements (AREs)GU-rich elements (GREs)U-rich elementsC-rich elementsPoly-pyrimidine tracts3' UTR regulatory elementsPoly-rich elements (PREs)

Small molecules or ASOs bind to the poly-rich sequences to displace RNA-binding proteins (RBPs), recruit nucleases for targeted degradation (e.g., via RIBOTACs), or modulate mRNA stability and translation efficiency by altering the transcript's half-life.