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The 3' untranslated region (3'UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon and extends to the poly-A tail. These regions serve as critical regulatory platforms containing binding sites for microRNAs (miRNAs) and RNA-binding proteins (RBPs), which control the stability, localization, and translation efficiency of the transcript (Mayr, 2019; Barrett et al., 2012). By modulating these interactions, the cell can rapidly adjust protein levels in response to physiological cues without the need for new transcription. In many pathological states, such as cancer, fibrosis, and neurological disorders, mutations or dysregulation within 3'UTRs can lead to the aberrant expression of oncogenes or the silencing of tumor suppressors (Conne et al., 2000; Siawrys et al., 2014). Therapeutically, targeting multiple mRNA 3'UTRs is a strategy often employed by microRNA-based drugs, where a single miRNA mimic or inhibitor can coordinately regulate an entire network of genes involved in a disease pathway (Rupaimoole & Slack, 2017). For example, miRNA mimics can restore the repressive function of a downregulated miRNA across its various target 3'UTRs to treat conditions like fibrosis or cancer. However, this multi-target approach necessitates careful design to minimize off-target effects and manage the potential for innate immune activation triggered by exogenous RNA molecules (Setten et al., 2019).
MicroRNA mimicry, microRNA antagonism, RNA interference (RNAi), and steric hindrance of RNA-binding protein or microRNA binding sites.
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