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FLASH GENE
Symbol DROSHA contributors: mct/npt - updated : 12-02-2015
HGNC name drosha, ribonuclease type III
HGNC id 17904
Location 5p13.3      Physical location : -
Synonym name
  • putative protein 241 which interacts with transcription factor sp1
  • ribonuclease type III, nuclear
  • drosha, double-stranded RNA-specific endoribonuclease
  • Synonym symbol(s) RN3, Etohi2, RANSE3L, RNASE3L, HSA242976, RNASEN
    EC.number 3.1.26.3
    DNA
    TYPE functioning gene
    STRUCTURE 131.68 kb     35 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    35 - 5424 159.2 1374 - 2007 17540974
    35 - 5389 155 1337 - 2007 17540974
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal protein-interaction domain, which associates with the RNA-binding protein NCBP1 and RNA Polymerase II
  • two Rnase III domains (RIIIDa and RIIIDb), that form an intramolecular dimer and cleave the 3' and 5' strands of the stem, respectively (Han 2004)
  • a DRBM (double stranded RNA binding) domain
  • a proline-rich, serine and arginine-rich domain
  • two RIBOcs domain
  • HOMOLOGY
    interspecies ortholog to murine Rnasen (96pc)
    Homologene
    FAMILY
  • ribonuclease III superfamily of double-stranded (ds) RNA-specific endoribonucleases
  • ribonuclease (RNase) III endonuclease protein family
  • CATEGORY enzyme , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleolus
    text a fraction is translocated to the nucleolus during the S phase of
    the cell cycle
    basic FUNCTION
  • executing the initial step of microRNA (miRNA) processing in the nucleus, that is cleavage of pre-miRNA to release pre-miRNA
  • involved in endonucleolytic cleavage to 5'-phosphomonoester
  • regulates cell proliferation and affects survival in esophageal cancer patients (Sugito 2006)
  • miRNA processing enzyme that are required for the maturation of miRNAs (Kuehbacher 2007)
  • significantly increased the expression of thrombospondin-1 (Kuehbacher 2007)
  • required in the first step of microRNA (miRNA) processing in the nucleus (Scotto 2008)
  • multiple functions for DROSHA and DICER1 in suppressing DNA damage in rapidly proliferating follicular matrix cells, facilitating catagen and maintaining follicular structures and their associated stem cells
  • is essential mainly for the canonical miRNA production, and DROSHA-mediated miRNA production is essential for normal spermatogenesis and male fertility
  • regulates neurogenesis by controlling NEUROG2 expression independent of microRNAs
  • DICER1 and DROSHA RNA products control DNA-damage response (DDR) activation and act independently from canonical microRNA-mediated translational repression mechanisms
  • potentially plays an important role breast cancer progression and assessment of its expression provides an independent predictor of patient outcome
  • cleaves double-stranded primary miRNA by interacting with double-stranded RNA binding protein DGCR8 and processes primary miRNA into precursor miRNA to participate in the miRNA biogenesis pathway
  • is required for vascular smooth muscle cell survival by targeting multiple signaling pathways
  • main RNase III-like enzyme involved in the process of microRNA (miRNA) biogenesis in the nucleus
  • RNA cleavage-independent function of Drosha in the regulation of human gene expression
  • promotes skipping of the overlapping exon in human cells independently of its cleavage function
  • CELLULAR PROCESS nucleotide, transcription, regulation
    protein, translation regulation
    PHYSIOLOGICAL PROCESS
    text
  • involved in pre-rRNA processing
  • ribosome biogenesis
  • RNA-mediated gene silencing
  • PATHWAY
    metabolism
    signaling
    general DROSHA-independent DGCR8/Pasha pathway that promotes proper morphology in multiple neuronal lineages
    a component
  • RNASEN -DGCR8 complex, also known as microprocessor, is essential for microRNA (miRNA) maturation, and functioning in mRNA stability control (Han 2009)
  • INTERACTION
    DNA
    RNA binding to double-stranded RNA
    small molecule nucleotide,
    protein
  • Sp1
  • cleaves the hairpins on the DGCR8 mRNA and destabilizes the mRNA, while the DGCR8 protein positively regulates RNASEN protein-protein interactionand may be involved in the stability control of other mRNAs (Han 2009)
  • excess RNASEN cleaves pasha/DGCR8 primary transcripts and leads to a reduction in pasha/DGCR8 mRNA levels and Pasha/DGCR8 synthesis (Kadener 2009)
  • mediates destabilization of LIN28A mRNA targets
  • intricate relationship between DGCR8 and DROSHA in which both proteins are required for binding and processing
  • specifically binds promoter-proximal regions of many human genes in a transcription-dependent manner
  • DGCR8 is an RNA-binding protein that interacts with DROSHA to produce pre-microRNA in the nucleus, while DICER generates not only mature microRNA, but also endogenous small interfering RNAs in the cytoplasm
  • DROSHA interacts with its cofactor DGCR8 to form the Microprocessor complex, which initiates microRNA (miRNA) maturation by cleaving hairpin structures embedded in primary transcripts
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in both the basal cell carcinomas, and squamous cell carcinomas (SCC) groups compared to those in the healthy controls
    constitutional       loss of function
    significantly reduces the number of cells positive for DNA-damage response (DDR) foci containing TP53BP1, the autophosphorylated form of ATM and the phosphorylated substrates of ATM and ATR
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS