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Ribonuclease III Drosha (DROSHA) is a double-stranded RNA-specific endoribonuclease and the catalytic core of the Microprocessor complex, essential for initiating canonical microRNA (miRNA) maturation in the nucleus. Drosha, together with its cofactor DGCR8, recognizes and cleaves hairpin structures within primary miRNA transcripts (pri-miRNAs), producing precursor miRNAs (pre-miRNAs) that are processed further by Dicer in the cytoplasm to generate mature miRNAs. These mature miRNAs then regulate target messenger RNAs via the RNA-induced silencing complex (RISC), modulating gene expression post-transcriptionally[1][2][3][5]. Beyond miRNA processing, Drosha cleaves hairpin structures embedded in protein-coding mRNAs to regulate their stability, participates in the DNA damage response, influences transcription and alternative splicing, and displays cytoplasmic antiviral activity upon viral infection-induced export from the nucleus[2]. Dysregulation of Drosha has been implicated in certain cancers, making it an emerging biomarker and potential therapeutic target[2]. Drosha's multidomain architecture includes proline-rich and arginine/serine-rich regions, two RNase III domains, a central domain, and a double-stranded RNA-binding domain, which together confer its specificity and activity in RNA processing[3][4][5].
Not applicable for drugs since there are no direct Drosha inhibitors or activators in clinical use; experimental inhibitors (small molecules targeting miRNA biogenesis) or gene-editing approaches may indirectly affect Drosha mechanisms.
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