Drosha

Drosha, ribonuclease type III
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2KHX
Identifiers
Symbols	DROSHA ; ETOHI2; HSA242976; RANSE3L; RN3; RNASE3L; RNASEN
External IDs	OMIM: 608828 MGI: 1261425 HomoloGene: 8293 GeneCards: DROSHA Gene
EC number	3.1.26.3
Gene ontology Molecular function • lipopolysaccharide binding • double-stranded RNA binding • ribonuclease III activity • protein binding • protein homodimerization activity • poly(A) RNA binding • metal ion binding • primary miRNA binding Cellular component • nucleus • nucleoplasm • nucleolus • microprocessor complex Biological process • gene expression • miRNA metabolic process • positive regulation of gene expression • rRNA catabolic process • production of siRNA involved in RNA interference • primary miRNA processing • pre-miRNA processing • ribosome biogenesis • defense response to Gram-negative bacterium • defense response to Gram-positive bacterium • RNA phosphodiester bond hydrolysis • RNA phosphodiester bond hydrolysis, endonucleolytic • regulation of miRNA metabolic process Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE RNASEN 218269 at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	29102	14000
Ensembl	ENSG00000113360	ENSMUSG00000022191
UniProt	Q9NRR4	Q5HZJ0
RefSeq (mRNA)	NM_001100412	NM_001130149
RefSeq (protein)	NP_001093882	NP_001123621
Location (UCSC)	Chr 5: 31.4 – 31.53 Mb	Chr 15: 12.82 – 12.94 Mb
PubMed search	[1]	[2]

Drosha is a Class 2 ribonuclease III enzyme that in humans is encoded by the DROSHA (formerly RNASEN) gene.

Function

Members of the ribonuclease III superfamily of double-stranded (ds) RNA-specific endoribonucleases participate in diverse RNA maturation and decay pathways in eukaryotic and prokaryotic cells. The RNase III Drosha is the core nuclease that executes the initiation step of microRNA (miRNA) processing in the nucleus.

The microRNAs thus generated are short RNA molecules that regulate a wide variety of other genes by interacting with the RNA-induced silencing complex (RISC) to induce cleavage of complementary messenger RNA (mRNA) as part of the RNA interference pathway. A microRNA molecule is synthesized as a long RNA primary transcript known as a pri-miRNA, which is cleaved by Drosha to produce a characteristic stem-loop structure of about 70 base pairs long, known as a pre-miRNA. Drosha exists as part of a protein complex called the Microprocessor complex, which also contains the double-stranded RNA binding protein Pasha (also called DGCR8). Pasha is essential for Drosha activity and is capable of binding single-stranded fragments of the pri-miRNA that are required for proper processing.

Human Drosha was cloned in 2000, when it was identified as a nuclear dsRNA ribonuclease involved in the processing of ribosomal RNA precursors. The other two human enzymes that participate in the processing and activity of miRNA are the Dicer and Argonaute proteins.

Both Drosha and Pasha are localized to the cell nucleus, where processing of pri-miRNA to pre-miRNA occurs. This latter molecule is then further processed by the RNase Dicer into mature miRNAs in the cell cytoplasm. Both Drosha and Dicer also participate in the DNA damage response.

Clinical significance

Drosha and other miRNA processing enzymes may be important in cancer prognosis. Both Drosha and Dicer can function as master regulators of miRNA processing and have been observed to be down-regulated in some types of breast cancer. However, the nature of the association between microRNA processing and tumorigenesis is unclear.