Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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drosha ribonuclease III(DROSHA) drosha ribonuclease III(DROSHA) Related Genes Homo sapiens
CHROMOSOME 5,
CYTOBAND 5p13.3,
ENSEMBL_GENE_ID ENSG00000113360,
GENERIF_SUMMARY identification of another RNase III, human Drosha, as the core nuclease that executes the initiation step of miRNA processing in the nucleus, human Drosha is a component of two multi-protein complexes; both components of the smaller complex, termed Microprocessor, are necessary and sufficient in mediating the genesis of miRNAs from the primary miRNA transcript, Data show that human Drosha selectively cleaves RNA hairpins bearing a large (>/=10 nucleotides) terminal loop., nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to generate mature miRNAs, processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences, Dicer gene expression in human breast cells is regulated by alternative promoter selection to alter the length and composition of the 5'-leader sequence of its mRNA, We found that RNASEN expression levels were enhanced in a fraction of esophageal cancers., Drosha may cleave intronic miRNAs between the splicing commitment step and the excision step, thereby ensuring both miRNA biogenesis and protein synthesis from a single primary transcript., identify specific miRNAs up-regulated in leukemias triggered by All1 fusions. All1 fusion protein-mediated recruitment of Drosha to target genes encoding miRNAs is demonstrated, miR-BHRF1-2 in 3' cleavage of BHRF1 mRNA in the cytoplasm and Drosha in cleavage of latency III EBNA and EBV replication-associated BHRF1 transcripts in the nucleus., Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha., Our findings indicate that levels of Dicer and Drosha mRNA in ovarian-cancer cells have associations with outcomes in patients with ovarian cancer., The Drosha-DGCR8 complex cleaves the hairpin in the DGCR8 mRNA and thus destabilizes the mRNA; DGCR8 stabilizes Drosha protein via protein interaction; this crossregulation between Drosha and DGCR8 may contribute to the control of miRNA biogenesis., The mRNA for microprocessor component DROSHA was found to be significantly upregulated in the dorsolateral prefrontal cortex in tissues from schizophrenic patients., a Microprocessor, containing the RNA binding protein Dgcr8 and RNase III enzyme Drosha, is responsible for processing primary microRNAs to precursor microRNAs, Report dysregulation of microRNA processing enzymes Drosha and Dicer in epithelial skin tumors when compared to healthy control samples., Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha., Findings of growth promotion by Drosher silencing implies its potential use as therapeutic targets for neuroblastoma., This study revealed for the first time that expression alterations of Dicer and Drosha are present in endometrial cancer tissue and could be potentially responsible for altered microRNAs profiles observed in this malignancy., the selectivity of Drosha action contributes greatly to the specificity and efficiency of miRNA biogenesis, Drosha, an endoribonuclease best known for its role in the biogenesis of microRNAs, can also function to directly regulate viral gene expression of Kaposi's sarcoma-associated herpesvirus, The authors report that Drosha cleavage of latency III BHRF1 RNA and cis-acting splicing effects inhibit splicing and inhibit BHRF1 RNA and protein expression., Our results suggest that Drosha, Dicer, and Ago2 are possibly implicated in colorectal carcinoma pathobiology, Drosha regulates human mesenchymal stem cells cell cycle progression through a miRNA independent mechanism, potentially by regulating rRNA processing., Low drosha expression is associated with breast cancer., Drosha and Dicer expression was dysregulation in nasopharyngeal carcinoma compared with healthy control samples., PTEN-mediated miR-21 regulation is achieved by inhibiting the interaction between the Drosha complex and RNH1, revealing previously unidentified role of PTEN in the oncogenic miR-21 biogenesis, mesenchymal stromal cells from MDS patients show low gene and protein expression of DICER1 and DROSHA which are involved in the microRNA biogenesis, as well as their target gene SBDS., The results showed that genetic variants of DROSHA may modify the risk of abnormal semen parameters, which could result in male infertility., DGCR8 and Drosha are targeted post-transcriptionally to chromosome 19 microRNA cluster pri-miRNAs as a preformed complex but dissociate separately., results provide novel evidence that Drosha, is probably involved in the pathobiology of human smooth muscle neoplasms, Data show that down-regulation of either Dicer or Drosha had no effect on the sensitivity of cells to irradiation., Rare Drosha splice variants are deficient in microRNA processing but do not affect general microRNA expression in cancer cells, Gene silencing of hepatitis B virus X protein by RNA interference significantly restored the expression of Drosha., Drosha, Dicer, Argonaute 1, and Argonaute 2 are differentially expressed at different metastatic sites in ovarian carcinoma compared with primary carcinomas., Dicer, Drosha, and Exportin 5 genes were up-regulated in bladder urothelial carcinoma compared to normal urothelium. Silencing these genes induced cell proliferation inhibition and apoptosis in bladder urothelial carcinoma cells., DGCR8-mediated cleavage of snoRNAs was independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Binding of DGCR8 to cassette exons is a new mechanism for regulation of alternatively spliced isoforms., A subset of Lin28 mRNA targets are destabilized in a Drosha-dependent manner., Drosha protein potentially plays an important role in breast cancer progression., Data indicate that tumour sample showed a significantly higher Drosha expression versus normal mucosa, while Dicer levels did not differ., miRNA regulatory effect is a heritable trait in humans; a polymorphism of the DROSHA gene contributes to the observed inter-individual differences., Primary microRNA structure reveals deviations from canonical double-stranded RNA structure in the stem adjacent to the Drosha cut site. The necessity of these deformable sites for efficient processing is demonstrated through Drosha processing assays., Levels of DICER1, DROSHA and five different miRNAs were measured in NSCLC specimens., Our results demonstrate a reduced nuclear expression of DROSHA in melanoma, It is a miRNA processing enzyme and altered in non-alcoholic fatty liver disease., RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 binds and regulates a large variety of cellular RNAs, Our results suggest that Drosha affects the biological activity of cervical cancer cells by regulating the expression of numerous tumour-associated proteins., results indicate a block of miRNA maturation at the DROSHA processing step, Ectopic AKAP95 stimulates expression of a chromosomal reporter gene in synergy with MLL1 or MLL2, whereas AKAP95 depletion impairs retinoic acid-mediated gene induction in embryonic stem cells, Acetylation of Drosha on those N-terminal lysine sites prevents Drosha ubiquitination, thereby preventing its degradation., If the distances are not optimal, Drosha tends to cleave at multiple sites, which can, in turn, generate multiple 5' isomiRs., DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR, Drosha regulates nascent gene transcription trhough interaction with CBP80 and RNA PolII., Low Drosha expression is associated with invasive breast carcinoma., The Microprocessor complex of Drosha and DGCR8 proteins, which is responsible for the processing of the primary transcripts during the generation of microRNAs, destabilizes the mRNA of Aurora kinase B., Change in Drosha expression can be a biologically relevant mechanism by which eukaryotic cells control miRNA profiles, The altered expression of Dicer and Drosha may serve as markers for disrupted miRNA biogenesis in Triple negative breast cancer, Association between recurrent pregnancy loss development and the polymorphism of the miRNA machinery gene RAN and combined genotype of DROSHA/DICER., conclude that Drosha can function like a splicing enhancer and promote exon inclusion. Our results reveal a new mechanism of alternative splicing regulation involving a cleavage-independent role for Drosha in splicing, The pri-miRNA stem, defined by internal and flanking structural elements, guides the binding position of Drosha-DGCR8, which consequently determines the cleavage site., data underscore the pivotal role of the miRNA biogenesis pathway in WT tumorigenesis, particularly the major miRNA-processing gene DROSHA, The involvement of E2F1-dependent DROSHA activation in pri-miRNA processing under DNA damage stress will provide further insight into the regulation of miRNA biosynthesis., To inhibit the expression of Drosha., DROSHA RNase IIIB mutations globally inhibit miRNA biogenesis through a dominant-negative mechanism in Wilms tumors., Drosha is upregulated in gestational diabetes., We aimed to evaluate the expression of the major components of microRNA biogenesis machinery including Drosha, Dicer and DiGeorge syndrome critical region gene 8 (DGCR8) in multiple sclerosis patients, EIF2C2, Dicer, and Drosha are more highly expressed in bladder carcinoma, promote the development of bladder cancer, and suggested a poor prognosis, in tumors with DGCR8 E518K and DROSHA exon 29 (miRNAPG-HS) mutations ... greater prevalence of tumors with blastemal predominant histology in patients with miRNAPG-HS and/or SIX1/2 Q177R mutations, Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain of SIX1 and SIX2 in tumors with high proliferative potential (18.1% of blastemal cases); mutations in the DROSHA/DGCR8 microprocessor genes, p38 MAPK directly phosphorylates Drosha at its N terminus promoting its nuclear export and degradation., Drosha protein was identified as a new component of dipeptide-repeat aggregates in frontotemporal lobar degeneration and tauopathy., The sequence and structural features of Drosha and Dicer cleavage sites., Together with a 23-amino acid peptide from DGCR8, DROSHA constitutes a minimal functional core. DROSHA serves as a "ruler" by measuring 11 bp from the basal ssRNA-dsRNA junction. DGCR8 interacts with the stem and apical elements through its dsRNA-binding domains and RNA-binding heme domain, respectively, allowing efficient and accurate processing., Variations in DROSHA rs10719 of Korean patients are significantly associated with their risk of colorectal cancer., DICER1 and DROSHA copy number variation may be an important mechanism of upregulation/downregulation of miRNAs in lung cancer, Results indicate the role of Drosha, Dicer and Ago2 proteins in the development of non-small cell lung carcinomas (NSCLC) and suggest that Dicer may be implicated in the progression of these tumors to advanced stages., Drosha expression was reduced gradually with the degrading histological differentiation of gastric adenocarcinoma, and the knock-down of Drosha expression could promote gastric adenocarcinoma cell invasion., DGCR8 and Drosha assemble into a heterotrimeric complex on RNA, comprising two DGCR8 molecules and one Drosha molecule., Gradual loss of cytoplasmic Drosha was accompanied by tumor progression in both gastric cancer tissues and cell lines, and was inversely associated with tumor volume (P = 0.002), tumor grade (P < 0.001), tumor stage (P = 0.018), and distant metastasis, Study reports the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8; DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor; overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part., we found that both the structural features of shmiR hairpins and the nucleotide sequence at Drosha and Dicer processing sites contribute to cleavage site selection and cleavage precision., An essential role of DROSHA in the canonical miRNA pathway,
OFFICIAL_GENE_SYMBOL DROSHA,
SP_COMMENT catalytic activity:Endonucleolytic cleavage to 5'-phosphomonoester., cofactor:Magnesium or manganese., function:Executes the initial step of microRNA (miRNA) processing in the nucleus, that is cleavage of pri-miRNA to release pre-miRNA. Involved in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA., online information:The dark side of RNA -Issue 87 of October 2007, similarity:Contains 1 DRBM (double-stranded RNA-binding) domain., similarity:Contains 2 RNase III domains., subcellular location:A fraction is translocated to the nucleolus during the S phase of the cell cycle., subunit:Interacts with Sp1., tissue specificity:Ubiquitous.,