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FLASH GENE
Symbol DGCR8 contributors: mct/npt/pgu - updated : 19-04-2017
HGNC name microprocessor complex subunit
HGNC id 2847
Corresponding disease
DEL22Q11 chromosome 22q11.2 microdeletion syndrome
DUP22Q11 chromosome 22q11.2 microduplication or triplication syndrome
Location 22q11.2      Physical location : 20.067.754 - 20.099.398
Genatlas name PASHA
Synonym name
  • chromosome 22 open reading frame 12
  • DiGeorge syndrome critical region gene 8
  • Synonym symbol(s) Gy1, C22orf12, DGCRK6, PASHA
    DNA
    TYPE functioning gene
    STRUCTURE 31.64 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - DGCR8 - HTF9C - qter
    Physical map
    HIRA 22q11.21-q11.23 HIR histone cell cycle regulation defective homolog A (S. cerevisiae) MRPL40 22q11.2 mitochondrial ribosomal protein L40 LOC128977 22q11.21 hypothetical protein LOC128977 UFD1L 22q11.21 ubiquitin fusion degradation 1-like CDC45L 22q11.2 CDC45 cell division cycle 45-like (S. cerevisiae) CLDN5 22q11.21 claudin 5 (transmembrane protein deleted in velocardiofacial syndrome) PNUTL1 22q11.21 peanut-like 1 (Drosophila) GP1BB 22q11.21 glycoprotein Ib (platelet), beta polypeptide LOC391296 22 similar to contains similarity to cell wall-plasma membrane linker protein~gene_id:MKA23.5 TBX1 22q11.21 T-box 1 GNB1L 22q11.2 guanine nucleotide binding protein (G protein), beta polypeptide 1-like FLJ21125 22q11.21 hypothetical protein FLJ21125 TXNRD2 22q11.21 thioredoxin reductase 2 COMT 22q11.2 catechol-O-methyltransferase ARVCF 22q11.21 armadillo repeat gene deletes in velocardiofacial syndrome DKFZp761P1121 22q11.21 hypothetical protein DKFZp761P1121 DGCR8 22q11.2 DiGeorge syndrome critical region gene 8 HTF9C 22q11.2 DiGeorge syndrome critical region gene 8 RANBP1 22q11.21 RAN binding protein 1 ZDHHC8 22q11.1 zinc finger, DHHC domain containing 8 LOC388849 22 LOC388849 FLJ32575 22q11.21 hypothetical protein FLJ32575 RTN4R 22q11.21 reticulon 4 receptor LOC388850 22 similar to proline dehydrogenase (oxidase) 1; proline oxidase 2; p53 induced protein; tumor protein p53 inducible protein 6 DGCR6L 22q11.2 DiGeorge syndrome critical region gene 6-like LOC391297 22 LOC391297 LOC284859 22q11.21 hypothetical gene supported by BC039313 GGT2 22q11 gamma-glutamyltransferase 2 LOC284874 22q11.21 hypothetical LOC284874 LOC388851 22 similar to phosphatidylinositol 4-kinase, catalytic, alpha polypeptide isoform 2; phosphatidylinositol 4-kinase, type II, alpha; phosphatidylinositol 4-kinase, type III, alpha; phosphatidylinositol 4-kinase 230 LOC388852 22 similar to hypothetical protein LOC388853 22 similar to Sushi domain (SCR repeat) containing LOC391298 22 similar to KIAA0649 gene product LOC388854 22 similar to Gamma-glutamyltranspeptidase 1 precursor (Gamma-glutamyltransferase 1) (CD224 antigen) LOC388855 22 hypothetical gene supported by BC039313 LOC388856 22 hypothetical gene supported by BC039313 LOC388857 22 similar to KIAA0649 gene product LOC391299 22 similar to Collagen alpha 1(II) chain precursor USP41 22q11.22 ubiquitin specific protease 41 ZNF74 22q11.21 zinc finger protein 74 (Cos52) SCARF2 22q11.21 scavenger receptor class F, member 2 FLJ14360 22q11.21 hypothetical protein FLJ14360 PCQAP 22q11.21 PC2 (positive cofactor 2, multiprotein complex) glutamine/Q-rich-associated protein
    RNA
    TRANSCRIPTS type
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 4536 86 773 - 2007 17704815
    13 - 4437 - 740 - 2007 17704815
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainforebraincerebral cortex highly Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text
  • eye lens, anterior segment, retina, choroid
  • expressed in the developing cortex
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two double-stranded RNA binding motifs (DSRM)
  • two WW motifs
  • a heme-binding domain (HBD, AAs 276–498), with a dimerization domain embedded in an independently folded heme-binding domain and directly contributing to association with heme
  • HOMOLOGY
    interspecies homolog to rattus LOC287954
    Homologene
    FAMILY
    CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,nucleolus
    text
  • locates at the nucleolus and small foci adjacent to splicing speckles in the nucleoplasm (localization of DGCR8 at the nucleolus was changed by the inhibition of RNA transcription)
  • basic FUNCTION
  • essential for biogenesis of miRNAs, functioning in the silencing of embryonic stem cell self-renewal that normally occurs with the induction of differentiation
  • recognizes primary microRNA (pre-miRNA) in two possible orientations
  • stabilizes the RNASEN (Drosha) protein via protein-protein interaction
  • component of the "microprocessor" complex that is essential for microRNA production, resulting in abnormal processing of specific brain miRNAs and working memory deficits
  • novel heme-binding protein with two cysteine side chains as axial ligands
  • native DGCR8 binds heme when expressed in eukaryotic cells
  • RNA-binding protein required for microRNA biogenesis
  • is required for vascular development through the regulation of vascular smooth muscle cells (VSMCs) proliferation, apoptosis, and differentiation
  • DGCR8-dependent miRs are indispensable for osteoclastic control of bone metabolism
  • is likely responsible for modulation of gene expression programs underlying myelin formation and maintenance as well as suppression of an injury-related gene expression program
  • acts likely as an adaptor to recruit the exosome complex to structured RNAs and induce their degradation
  • 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
  • noncanonical function of DGCR8 in the modulation of the alternative splicing of TCF7L1 mRNA in addition to its established function in microRNA biogenesis
  • RNA binding protein that canonically functions with DROSHA to mediate microRNA processing, in the repair of UV-induced DNA lesions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    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
  • component of the microprocessor complex essential for microRNA production, resulting in abnormal processing of specific brain miRNAs and working memory deficits
  • intricate relationship between DGCR8 and DROSHA in which both proteins are required for binding and processing
  • INTERACTION
    DNA
    RNA binding, binds RNA nonspecifically
    small molecule
    protein
  • crossregulation between RNASEN and DGCR8 may contribute to the homeostatic control of miRNA biogenesis
  • interacting with Nucleolin, ILF3 and others, most of which appeared to be involved in the RNA processing or RNA transportation
  • binds heme through a heme-binding domain (HBD, amino acids 276–498) that can be expressed in a soluble, heme-bound form in the absence of other domains
  • heme may bind and activate DGCR8 while the signal is turned off through protein degradation
  • caspases cleave and inhibit the microRNA processing DGCR8
  • DGCR8 is a direct interactor of TCF7L1 mRNA, a core component of the pluripotency network
  • physically interacted with ERCC6 and RNA polymerase II
  • 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
    repressed by negatively regulated by the RNASEN-DGCR8 complex through mRNA cleavage
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL22Q11 , DUP22Q11
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    resulted in smaller dendritic spines and simpler dendritic tree and impaired sensorimotor gating and acquisition of a spatial working memory–dependent task
    constitutional       loss of function
    associated with altered short-term plasticity and is a neural substrate underlying the cognitive dysfunction and the increased risk for schizophrenia associated with the 22q11.2 microdeletions
    tumoral       gain of function
    may be involved in tumorigenesis and aggressiveness of invasive ductal breast carcinoma (IDC)
    constitutional   deletion    
    conditional gene deletion of the essential miRNA-processing enzyme Dgcr8 in the developing renal tubular system results in severe developmental defects and kidney failure
    constitutional       loss of function
    senescence triggered by DGCR8 loss is accompanied by the upregulation of the cell-cycle inhibitor CDKN1A
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    may serve as future therapeutic target in invasive ductal breast carcinoma (IDC)
    ANIMAL & CELL MODELS
  • Dgcr8+/- mice display reduced expression of a subset of microRNAs in the prefrontal cortex, a deficit that emerges over postnatal development
  • deficiency in Dgcr8-dependent canonical microRNAs causes infertility due to multiple abnormalities during uterine development in mice