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FLASH GENE
Symbol DICER1 contributors: mct/shn - updated : 26-08-2018
HGNC name dicer 1, ribonuclease type III
HGNC id 17098
Corresponding disease
DICER1S DICER1 syndrome
Location 14q32.13      Physical location : 95.552.564 - 95.623.759
Synonym name
  • K12H4.8-like helicase-moi
  • homolog of Drosophila Dicer
  • dicer 1, double-stranded RNA-specific endoribonuclease
  • helicase with RNase motif
  • Dicer1, Dcr-1 homolog (Drosophila)
  • dicer 1, double-stranded RNA-specific endoribonuclease
  • endoribonuclease Dicer
  • helicase MOI
  • helicase with RNAse motif
  • helicase-moi
  • Synonym symbol(s) HERNA, KIAA0928, Dicer, K12H4.8-LIKE, DCR1, MNG1
    EC.number 3.1.26.-
    DNA
    TYPE functioning gene
    STRUCTURE 71.20 kb     28 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure promoter with two conserved E-box elements, the MITF consensus binding sequences, within 2 kb upstream of the DICER1 transcription start site
    MAPPING cloned Y linked N status confirmed
    Map cen -D14S1054 - D14S1434 - DICER1 - D14S1030 - D14S996 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    27 splicing 10323 218 1922 - 2005 15987463
    28 splicing 10267 218 1922 - 2005 15987463
    differing in the 5' UTR compared to variant 1
    26 splicing 9921 - 1829 in neuroblastoma cells and in cells induced to neuronal differentiation, whereas it was not detectable in other cell lines or in normal tissues 2010 20615407
  • also called t-Dicer
  • lacking the dsRNA-binding domain and is defective in one of the two RNase III catalytic centers
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   moderately Homo sapiens
    Endocrineneuroendocrinepituitary  highly
     pancreas   moderately
    Lymphoid/Immunelymph node   predominantly
    Nervousnervecranial nerve  moderately
    Reproductivefemale systembreastmammary gland highly
     female systemplacenta  moderately Homo sapiens
     male systemprostate  moderately
    Respiratorylung    
     respiratory tracttrachea  moderately
    Skin/Tegumentskin   moderately
    Urinarybladder   moderately
     kidney   moderately Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscular   moderately
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, highly in umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an helicase ATP-binding domain
  • an helicase C-terminal domain
  • a PAZ domain
  • two RNase III domains
  • a DRBM (double-stranded RNA-binding) domain
  • a unique amino acid sequence of 127 amino acids in the RIBOc-A domain as a binding site to Argonaute proteins
  • a basic 5prime pocket positioned in close proximity to the 3prime pocket on the same face of the DICER1 protein
  • mono polymer heteromer , trimer
    HOMOLOGY
    interspecies ortholog to DICER1, Pan troglodytes
    ortholog to Dicer1, Rattus norvegicus
    ortholog to Dicer1, Mus musculus
    Homologene
    FAMILY
  • ribonuclease (RNase) III endonuclease protein family
  • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    text colocalized with calreticulin, a resident protein of the endoplasmic reticulum
    basic FUNCTION
  • play an essential role in mammalian siRNA-mediated posttranscriptional gene silencing (
  • involved in cleaving double-stranded RNA in the RNA interference (RNAi) pathway
  • producing 21 to 23 bp dsRNAs (siRNAs) which target the selective destruction of homologous RNAs
  • acting as an endonuclease
  • playing a critical role in maintaining the proliferating pool of chondrocytes through regulation of chondrocyte proliferation and inhibition of premature differentiation to postmitotic hypertrophic chondrocytes
  • required for maintenance of proliferating chondrocytes in the growth plate
  • playing an essential role in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions
  • also involved in the assembly of the RNA-induced silencing complex (RISC) that mediates the effector steps of RNA silencing
  • essential for turnover of a substantial subset of maternal transcripts that are normally lost during oocyte maturation and as central to a regulatory network that controls oocyte gene expression programs and that promotes genomic integrity in a cell type notoriously susceptible to aneuploidy (
  • miRNA processing enzyme that are required for the maturation of miRNAs
  • significantly increased the expression of thrombospondin-1
  • transient reduction of the miRNA-regulating enzyme Dicer impairs angiogenesis
  • essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions (
  • prevalent role of DICER1 and EIF2C4 in neural cell differentiation
  • may be an important haploinsufficient tumor suppressor gene
  • plays a crucial role in melanocyte survival involving, in part, posttranscriptional processing of miR-17 which leads to downregulation of the proapoptotic protein BCL2L11
  • ribonuclease playing a key role in the biogenesis of microRNAs and small interfering RNAs
  • key role of DICER1 in maintaining retinal pigmented epithelium (RPE) cell health
  • cellular functions dependent on DICER expression are not required for the early steps in CD8+ T-cell activation, but are essential for their survival and accumulation
  • essential for the CD8+ effector T-cell response
  • DICER1/miRNAs also control CD8+ T-cell activation, proliferation, migration, and accumulation during acute infection
  • regulates CD8+ T-cell activation and proliferation, and controls CD69 retention and cell migration in activated CD8+ T cells
  • key mediator of miRNA biosynthesis, within the optic cup in overlapping yet distinct spatiotemporal patterns
  • required for vascular development and regulates vascular remodeling by modulating VSMC (vascular smooth muscle cells) proliferation and differentiation
  • key regulator in siRNA and miRNA biogenesis
  • essential during early retinal development (
  • DDX3X and DICER1 are also required in promoting chromosome segregation and chromosomal localization of NCAPH (human homolog of Barr)
  • accurate processing by DICER1 is crucial for the functionality of microRNAs (miRNAs)
  • appears to be the first gene implicated in the etiology of cervix embryonal rhabdomyosarcoma (cERMS), and primitive neuroectodermal tumor (cPNE)
  • 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
  • rate-limiting enzyme for microRNA (miRNA) synthesis
  • controls proadipogenic genes such as CEBPA and PPARG in the early, but not in the late, stage of adipogenesis via regulation of miRNA synthesis
  • is an essential endogenous negative regulator of NLRP3 inflammasome activation, and its deficiency leads to Alu RNA-mediated, MYD88-dependent, microRNA-independent RPE degeneration
  • required for the biogenesis of several small RNA species
  • DICER1 and DROSHA RNA products control DNA-damage response (DDR) activation and act independently from canonical microRNA-mediated translational repression mechanisms
  • is a critical regulator of post-transcriptional gene silencing
  • hypoxic down-regulation of DICER1 plays a significant role in maintaining the cellular response to hypoxia by preserving the expression of HIF1A and HIF2A via microRNA regulation
  • cytoplasmic RISC proteins PRKRA, TARBP2, and DICER1 are steroid receptor RNA activator (SRA) binding nuclear receptor (NR) coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression
  • CELLULAR PROCESS nucleotide, transcription, maturation
    PHYSIOLOGICAL PROCESS
    text processes double-stranded RNAs to 21 nt small interfering RNAs during RNA interference, and excises microRNAs from precursor hairpins
    PATHWAY
    metabolism
    signaling
  • biogenesis of miRNAs
  • a component
  • PRKRA is associated with a ~500 kDa complex that contains DICER1, AGO2, and TARBP2 and it associates with DICER1 to facilitate the production of small interfering RNA
  • DICER1 and Argonaute 1-4 proteins (EIF2C1, EIF2C2, EIF2C3, EIF2C4) are key components of the cytoplasmic enzyme machinery responsible for biogenesis and performance of microRNAs
  • INTERACTION
    DNA
    RNA binding
    small molecule nucleotide,
  • ATP
  • protein
  • eukaryotic translation initiation factor 2C 1, EIF2C1 (
  • PIWIL2, PIXWIL3, PIWIL4, AGO3, AGO4 (
  • PAZ PIWI domain proteins and argonaut 2, AGOA (
  • PIWIL1
  • HIV-1 TAR RNA-binding protein, TRBP and protein kinase, interferon-inducible double stranded RNA dependent activator, PACT (
  • Argonaute family proteins through the small binding site within RIBOc-A domain
  • decreased DICER1 expression induces FN1 expression via an EGR1-dependent manner
  • TP63 binds to and transactivates the DICER1 promoter, demonstrating direct transcriptional regulation of DICER1 by TAP63
  • required, at least in part, to promote the mitotic localization of DDX3X and NCAPH in the regulation of chromosome segregation
  • DICER1 associates with NUP153(this association is detected predominantly in the cytoplasm but is also clearly distinguishable at the nuclear periphery), and NUP153 plays a crucial role in the nuclear localization of the DICER1 protein
  • potential antagonism between ZC3H12A and DICER1 function in human cancer
  • AGO2, PRKRA and TARBP2 were required for the efficient functioning of DICER1 in cells, and likely one of the roles of these proteins is to assure better synchronization of cleavages triggered by two RNase III domains of DICER1
  • might have important roles in the expression of adipogenic genes including PPARG and CEBPA via regulation of the expression of miRNAs at the early, but not the late, stage of adipocyte differentiation
  • endogenous non-coding RNA-induced NLRP3 inflammasome activation results from DICER1 deficiency in a non-immune cell
  • VHL-dependent down-regulation of DICER1 is key to the expression and function of HIF1A subunits
  • DICER1 expression is at least in part dependent on VHL
  • CKAP4 is required for stabilizing DICER1 protein and for optimal regulation of a reporter gene coupled to the 3prime untranslated region of HMGA2 mRNA in human cells
  • PRKRA and TARBP2 have distinct effects on DICER1-mediated dsRNA processing
  • CTNNB1 is a critical regulator in the development of behavioural resilience, activating a network that includes DICER1 and downstream microRNAs
  • interface residues conserved between TARBP2 and PRKRA show that the proteins bind to DICER1 in a similar manner and by mutual exclusion
  • DGCR8 is an RNA-binding protein that interacts with DROSHA to produce pre-microRNA in the nucleus, while DICER1 generates not only mature microRNA, but also endogenous small interfering RNAs in the cytoplasm
  • MOV10-FMR1-AGO2 complex regulates DICER1 expression, revealing a novel mechanism for regulation of miRNA production required for normal neuronal morphology
  • cell & other
    REGULATION
    activated by MITF (via its transcriptional targeting by the melanocytic transcription factor MITF during differentiation, through a novel mechanism)
    induced by strongly induced during melanocyte differentiation via direct transcriptional regulation by MITF
    inhibited by RNAi in human cells, which up-regulates major histocompatibility complex class I-related molecules A and B (MICA and MICB)
    Other is regulated in hypoxia via VHL-dependent processes
    ASSOCIATED DISORDERS
    corresponding disease(s) DICER1S
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    results in a reduction in the number of proliferating chondrocytes through two distinct mechanisms: acceleration of differentiation into postmitotic hypertrophic chondrocytes and reduction in chondrocyte proliferation
    constitutional     --low  
    in end-stage human DCM and failing hearts
    constitutional germinal mutation      
    heterozygous gene mutation in 11 multiplex pleuropulmonary blastoma families
    constitutional germinal mutation      
    in familial cystic nephroma
    constitutional     --low  
    disruption of Dicer expression compromised most but not all miRNA expression we examined indicating the role of other mechanisms involved in miRNA maturation
    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 to gastric cancer
    Variant & Polymorphism SNP SNPs rs3742330 were associated with susceptibility to gastric cancer
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • deleted Dicer in VSMCs of mice, which caused a developmental delay that manifested as early as embryonic day E12.5, leading to embryonic death between E14.5 and E15.5 due to extensive hemorrhage in the liver, brain, and skin
  • an initial build-up of miRNA levels, produced by maternal Dicer1, in homozygous dicer1 mutants, but miRNA accumulation stopped after a few days is observed in target-selected inactivation of the dicer1 gene in zebrafish (
  • loss of Dicer1 in mice lead to lethality early in development, with Dicer1-null embryos depleted of stem cells (
  • Dicer-null embryonic stem cells are viablebut are completely defective in RNA interference and the generation of microRNAs (
  • epidermal organization is perturbed in embryonic skin progenitors conditionally targeted Dicer1 gene ablation (
  • Specific deletion of dcr-1 in the T cell lineage resulted in impaired T cell development and aberrant T helper cell differentiation and cytokine production (
  • mouse oocytes lacking Dicer arrest in meiosis I with multiple disorganized spindles and severe chromosome congression defects (
  • ablation of Dicer in mouse dopaminoceptive neurons leads to a range of phenotypes including ataxia, front and hind limb clasping, reduced brain size, and smaller neurons (
  • Dicer-null growth plates show a progressive reduction in the proliferating pool of chondrocytes, leading to severe skeletal growth defects and premature death of mice (
  • mouse cardiac-specific knockout of Dicer leads to rapidly progressive dilated cardiomyopathy, heart failure, and postnatal lethality (
  • conditional knock-out mouse for Dicer1 demonstrated that miRNAs are crucial for postnatal survival of functional hair cells of the inner ear (
  • deletion of Dicer1 in mouse oligodendrocyte lineage cells leads severe myelinating deficits despite an expansion of the oligodendrocyte progenitor pool (
  • DICER1 knockdown induces accumulation of Alu RNA in human retinal pigmented epithelium (RPE) cells and Alu-like B1 and B2 inducing RPE cytotoxicity and degeneration (
  • Massive death of retinal progenitor cells occurred during embryogenesis, resulting in microphthalmia, and most retinal cells had disappeared by postnatal day 14 in Dicer-CKO mice (