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FLASH GENE

Symbol

DGCR8

contributors: mct/npt/pgu - updated : 19-04-2017

HGNC name	microprocessor complex subunit
HGNC id	2847

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_022720 14 - 4536 NP_073557 86 773 - 2007 17704815 NM_001190326 13 - 4437 NP_001177255 - 740 - 2007 17704815

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain forebrain cerebral 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer reproductive breast 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