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Ribonuclease III Drosha (DROSHA)

Target
DROSHA
Molecular classification
Enzyme, Ribonuclease III family, Double-stranded RNA-specific endoribonuclease, Nuclear RNase III
01

Overview

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].

Other names
Ribonuclease 3RN3RNASE3LRNASENRNase IIIEtohi2HSA242976p241double-stranded RNA-specific endoribonucleasenuclear RNase III Droshaputative ribonuclease IIIdroshaETOHI2protein DroshaSp1-interacting protein p241
02

Mechanism of action

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.

03

Biological functions

Initiation of microRNA (miRNA) processingCleavage of primary miRNA (pri-miRNA) to precursor miRNA (pre-miRNA)Post-transcriptional regulation of gene expression via miRNAsDestabilization of certain mRNAs by cleaving embedded hairpinsModulation of transcription (activation) and co-transcriptional RNA processingRegulation of alternative splicing and interaction with splicing machineryResponse to DNA damageAntiviral activity against RNA viruses
04

Disease associations

Cancer (mutations or dysregulation implicated in oncogenesis and tumor suppression via miRNA pathways)Other (developmental processes, possible roles in neurodegeneration and viral infection)
05

Safety considerations

Modulating Drosha may result in widespread disruption of miRNA biogenesis, potentially affecting normal cell function, differentiation, and immune responseTherapeutic targeting may risk off-target effects due to essential roles in RNA metabolism
06

Biomarkers

Drosha expression level (occasionally used for cancer subtype classification, prognosis, and prediction of miRNA-based pathway activity)

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