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The Dicer–TRBP complex is a fundamental multi-protein assembly in the RNA interference (RNAi) pathway, primarily composed of the RNase III enzyme Dicer and its essential cofactor, the TAR RNA-binding protein (TRBP). This complex is responsible for the precise processing of precursor microRNAs (pre-miRNAs) and long double-stranded RNAs (dsRNAs) into mature miRNAs and small interfering RNAs (siRNAs), respectively (UniProt, 2024). TRBP plays a critical role in stabilizing Dicer and enhancing its catalytic efficiency, while also facilitating the recruitment of Argonaute proteins to form the RNA-induced silencing complex (RISC) (PubMed: 24508331). Dysregulation of the Dicer–TRBP complex is frequently observed in various human malignancies, where altered miRNA profiles contribute to oncogenesis, tumor progression, and poor clinical outcomes (PubMed: 22431510). Consequently, the complex has emerged as a significant therapeutic target, with research focusing on small molecules like enoxacin that can modulate its activity to restore normal miRNA biogenesis (PubMed: 18278052). However, targeting such a central regulatory hub presents substantial challenges, including the risk of widespread off-target effects on global gene expression and potential systemic toxicity.
Modulation of microRNA biogenesis and enhancement of RNA interference efficiency
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