Affinage

DGCR8

Microprocessor complex subunit DGCR8 · UniProt Q8WYQ5

Length
773 aa
Mass
86.0 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DGCR8 is the essential RNA-recognition subunit of the nuclear Microprocessor complex that initiates microRNA biogenesis by cleaving primary miRNA transcripts. Together with the endonuclease Drosha, DGCR8 forms a ~650 kDa complex in which its tandem dsRNA-binding domains and dimeric heme-binding domain (Rhed) directly contact pri-miRNA substrates, functioning as a molecular ruler that measures ~11 bp from the stem–single-stranded RNA junction to position the Drosha cleavage site; ferric heme binding through a unique double-cysteine ligation induces a conformational change in DGCR8 that is required for high-fidelity substrate recognition and processing (PMID:16751099, PMID:21454614, PMID:29170488, PMID:32220646). DGCR8 activity is tuned by post-translational modifications—ERK phosphorylation stabilizes the protein, HDAC1-mediated deacetylation enhances its RNA-binding affinity, and SUMOylation by USP36 promotes pri-miRNA engagement—while its own mRNA is homeostatically down-regulated by Microprocessor cleavage of hairpins in the DGCR8 5′ UTR (PMID:24239349, PMID:22222205, PMID:36950067, PMID:19135890). Beyond canonical miRNA processing, DGCR8 performs Drosha-independent functions: it recruits the nuclear exosome to structured RNAs such as snoRNAs and telomerase RNA, regulates alternative splicing, maintains heterochromatin organization through interaction with Lamin B1/KAP1/HP1γ, facilitates UV-induced transcription-coupled nucleotide excision repair via CSB, and promotes DNA double-strand break repair through ATM-dependent stabilization and RNF168 recruitment (PMID:26687677, PMID:28100686, PMID:31350386, PMID:28380355, PMID:34188037).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2004 High

    Identification of DGCR8 as the obligate partner of Drosha in a nuclear pri-miRNA processing complex (Microprocessor) resolved how metazoan cells initiate miRNA biogenesis.

    Evidence Co-IP, biochemical fractionation, RNAi knockdown, and in vitro reconstitution of pri-miRNA cleavage in human cells

    PMID:15574589

    Open questions at the time
    • Mechanism by which DGCR8 recognizes pri-miRNA substrates was unknown
    • Stoichiometry and structural architecture of the complex were unresolved
  2. 2006 High

    Establishing that DGCR8—not Drosha—is the direct pri-miRNA-binding subunit and acts as a molecular anchor measuring distance from the stem–ssRNA junction defined the substrate-recognition logic of Microprocessor.

    Evidence In vitro RNA-binding assays with purified DGCR8, pri-miRNA mutational analysis, domain deletion/localization studies

    PMID:16751099 PMID:16963499

    Open questions at the time
    • Atomic-resolution structure of DGCR8 dsRBDs on pri-miRNA was lacking
    • Role of the N-terminal/heme-binding region in RNA recognition was unclear
  3. 2007 High

    Crystal structure of the DGCR8 dsRBD core and genetic knockout in mouse ES cells established the structural basis of dsRNA recognition and demonstrated that DGCR8 is essential for all miRNA production and proper stem cell differentiation.

    Evidence X-ray crystallography with FRET/mutagenesis validation; Dgcr8 knockout ES cells with miRNA profiling and differentiation assays

    PMID:17259983 PMID:17704815

    Open questions at the time
    • Structure of the heme-binding dimerization domain was unknown
    • How Drosha and DGCR8 coordinate cleavage site selection at atomic resolution was unresolved
  4. 2009 High

    Discovery of a homeostatic feedback loop—Microprocessor cleaves hairpins in the DGCR8 mRNA while DGCR8 stabilizes Drosha protein—explained how cells maintain balanced Microprocessor stoichiometry.

    Evidence In vitro cleavage reconstitution, luciferase reporters, RNAi of Drosha, mRNA/protein stability measurements

    PMID:19135890 PMID:19383765

    Open questions at the time
    • Physiological conditions under which the feedback set point shifts were not defined
    • Whether other hairpin-containing mRNAs are similarly regulated was unexplored
  5. 2011 High

    Demonstration that DGCR8 binds ferric heme through an unprecedented double-cysteine ligation, with heme being required for pri-miRNA processing activity, revealed a unique cofactor dependency in RNA processing.

    Evidence Electronic absorption, magnetic circular dichroism, EPR spectroscopy, selenomethionine substitution, and in vitro processing assays

    PMID:21454614 PMID:22308374

    Open questions at the time
    • How heme binding induces the activating conformational change was unknown
    • Physiological regulation of heme occupancy in DGCR8 was not addressed
  6. 2012 High

    Transcriptome-wide HITS-CLIP and identification of HDAC1 as a Microprocessor component expanded DGCR8 function beyond pri-miRNAs to mRNA regulation, snoRNA cleavage, and alternative splicing, and revealed that deacetylation of DGCR8 dsRBDs enhances RNA-binding affinity.

    Evidence HITS-CLIP deep sequencing with knockdown validation; Co-IP of HDAC1 with Microprocessor plus in vitro deacetylation and RNA-binding assays

    PMID:22222205 PMID:22796965

    Open questions at the time
    • Identity of the endonuclease partnering with DGCR8 for Drosha-independent snoRNA cleavage was not established
    • Specific acetylation sites on DGCR8 dsRBDs were not mapped
  7. 2013 High

    Mapping of ERK-mediated phosphorylation sites on DGCR8 and demonstration that phosphorylation stabilizes the protein linked mitogenic signaling to miRNA biogenesis output.

    Evidence Phosphoproteomics of full-length DGCR8, phosphomimetic/phosphomutant functional assays, miRNA profiling, proliferation assays

    PMID:24239349

    Open questions at the time
    • Which individual phosphosites are most critical for stability vs. activity was not fully resolved
    • Whether other kinases contribute to basal DGCR8 phosphorylation was unknown
  8. 2014 High

    Identification of the Rhed as a direct RNA-contact domain and demonstration that MeCP2 competes with Drosha for DGCR8 binding revealed dual regulatory mechanisms at the substrate-recognition and complex-assembly levels.

    Evidence In vitro reconstitution with Rhed domain mutants and stoichiometry analysis; Co-IP of MeCP2–DGCR8, in vitro processing with interaction-deficient MeCP2 mutants, neuronal morphology assays

    PMID:24636259 PMID:24910438

    Open questions at the time
    • Atomic structure of Rhed bound to pri-miRNA was not available
    • Whether MeCP2 regulation of DGCR8 operates on all or select pri-miRNAs was unclear
  9. 2015 High

    Discovery that DGCR8 recruits the nuclear exosome to structured RNAs independently of Drosha, and that ABL kinase phosphorylates DGCR8 at Y267 to selectively promote pri-miRNA processing upon DNA damage, established DGCR8 as a multifunctional RNA-processing adaptor modulated by damage signaling.

    Evidence Reciprocal Co-IP of DGCR8 with exosome subunits, RNAi knockdown, snoRNA/hTR processing assays; in vitro ABL kinase assay, Y267F mutant, RNA cross-linking

    PMID:26126715 PMID:26687677

    Open questions at the time
    • How DGCR8 discriminates exosome substrates from Microprocessor substrates was unresolved
    • Structural basis of ABL-phosphorylated DGCR8 preferentially engaging select pri-miRNAs was unknown
  10. 2017 High

    Mechanistic dissection showed that heme induces a conformational change (not oligomerization change) in DGCR8 for high-fidelity processing; simultaneously, miRNA-independent roles in heterochromatin maintenance via Lamin B1/KAP1/HP1γ, alternative splicing of Tcf7l1, and UV-induced TC-NER via CSB interaction were established.

    Evidence In vitro heme manipulation with conformational analysis; Co-IP and senescence rescue with N-terminal truncation mutant in hMSCs; RNA-IP and phosphomutant complementation in Dgcr8-KO mESCs; phospho-S153 mutant epistasis with NER factors and Co-IP with CSB/RNA Pol II

    PMID:28100686 PMID:28380355 PMID:29170488 PMID:31350386

    Open questions at the time
    • Whether heterochromatin maintenance requires DGCR8 RNA-binding activity was unclear
    • How DGCR8 is recruited to UV lesions and whether it acts catalytically or as a scaffold was unknown
  11. 2020 High

    Cryo-EM structure of the complete Microprocessor–pri-miRNA complex confirmed the molecular-ruler model, showing DGCR8 dsRBDs spanning the two junctions, while identification of ERH as a new Microprocessor component explained 'cluster assistance' for suboptimal pri-miRNAs in polycistronic transcripts.

    Evidence Cryo-EM structural determination with Belt/Wedge mutagenesis; crystal structure of ERH–DGCR8 N-terminus, ERH knockdown with in vitro and cellular miRNA profiling

    PMID:32220646 PMID:33035348

    Open questions at the time
    • Full-length DGCR8 structure including the Rhed in the context of the holo-complex was not resolved
    • Mechanism of cluster assistance at a structural level was not determined
  12. 2021 High

    ATM-mediated phosphorylation at S677 stabilizes DGCR8 via USP51 deubiquitination and enables DGCR8 to recruit RNF168 for H2A ubiquitination at DNA double-strand breaks, establishing a Drosha-independent role in DSB repair signaling.

    Evidence ATM kinase assay, USP51 deubiquitination assay, S677A mutant, Co-IP of DGCR8–RNF168–MDC1, H2A ubiquitination and radioresistance assays

    PMID:34188037

    Open questions at the time
    • Whether DGCR8's RNA-binding capability contributes to DSB repair was not tested
    • Structural basis of the DGCR8–RNF168 interaction was unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full atomic-resolution structure of heme-bound DGCR8 in complex with Drosha and pri-miRNA, the identity of the endonuclease(s) partnering with DGCR8 for Drosha-independent RNA cleavage, and the mechanisms by which DGCR8 partitions between its canonical miRNA-processing and noncanonical chromatin/DNA-repair functions remain to be determined.
  • No complete holo-Microprocessor structure with Rhed and heme resolved
  • Endonuclease identity for Drosha-independent snoRNA cleavage not established
  • Decision logic for DGCR8 allocation among its multiple nuclear functions is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005730 nucleolus 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-73894 DNA Repair 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-4839726 Chromatin organization 1
Partners
CSBDROSHAERHHDAC1LMNB1MECP2RNF168USP51
Complex memberships
DGCR8–nuclear exosome complexERH–DGCR8 subcomplexMicroprocessor (Drosha–DGCR8)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 DGCR8 interacts directly with Drosha to form a ~650 kDa nuclear complex (Microprocessor) that cleaves pri-miRNAs to release pre-miRNAs; DGCR8 contains two dsRNA-binding domains and is an essential component of this processing complex, demonstrated by RNAi knockdown and biochemical reconstitution. Co-immunoprecipitation, biochemical fractionation, RNAi knockdown, in vitro reconstitution assay Genes & development High 15574589
2006 Purified DGCR8, but not Drosha, directly and specifically binds pri-miRNAs; the flanking single-stranded RNA segments of the pri-miRNA are critical for DGCR8 binding; DGCR8 functions as a molecular anchor measuring ~11 bp distance from the stem-ssRNA junction to determine the Drosha cleavage site. In vitro RNA-binding assays with purified protein, mutational analysis of pri-miRNA substrates, biochemical reconstitution Cell High 16751099
2006 The tandem dsRNA-binding domains (dsRBDs) of DGCR8 are responsible for direct and stable interaction with pri-miRNAs; the middle domain of Drosha interacts with the conserved C-terminal domain of DGCR8 to stabilize Drosha; the N-terminal region of DGCR8 upstream of its dsRBDs is critical for nuclear localization but not for pri-miRNA processing. Domain deletion/mutant analysis, co-immunoprecipitation, subcellular localization imaging Nucleic acids research High 16963499
2007 Crystal structure of human DGCR8 core (residues 493-720) reveals two dsRBDs arranged with pseudo two-fold symmetry tightly packed against a C-terminal helix; the H2 helix in each dsRBD is important for pri-miRNA recognition; FRET and mutational analyses support two possible orientations for DGCR8 core binding to pri-miRNA. X-ray crystallography, FRET, mutational analysis, in vitro processing assay Nature structural & molecular biology High 17704815
2007 DGCR8 is required for miRNA biogenesis in mouse embryonic stem cells; DGCR8-deficient ES cells fail to produce mature miRNAs and cannot properly silence self-renewal upon induction of differentiation, demonstrating an essential role in the miRNA processing pathway. Dgcr8 gene knockout in mouse ES cells, small RNA profiling, differentiation assays Nature genetics High 17259983
2007 DGCR8 localizes to the nucleolus and to small foci adjacent to splicing speckles; nucleolar localization depends on active RNA transcription; DGCR8 forms distinct protein complexes including DROSHA/DGCR8, DGCR8/Nucleolin (RNA-dependent), DGCR8/ILF3, and ILF3/XPO5, identified by immunoprecipitation and mass spectrometry. Immunoprecipitation, mass spectrometry, immunofluorescence, immunoelectron microscopy, transcription inhibition Experimental cell research Medium 17765891
2009 The Drosha-DGCR8 complex (Microprocessor) cleaves hairpin structures embedded within the DGCR8 mRNA 5'UTR and coding region, thereby destabilizing the DGCR8 mRNA; conversely, DGCR8 stabilizes Drosha protein via protein-protein interaction, establishing a homeostatic cross-regulatory loop. In vitro cleavage assay, mRNA stability analysis, RNAi knockdown, protein interaction assay, microarray analysis Cell High 19135890
2009 The Microprocessor negatively regulates DGCR8 expression by cleaving a hairpin located in the 5'UTR of DGCR8 mRNA; demonstrated by in vitro reconstitution and a luciferase reporter assay showing that the DGCR8 5'UTR confers Microprocessor-dependent repression; Drosha knockdown increases DGCR8 mRNA and protein levels. In vitro cleavage reconstitution, luciferase reporter assay, RNAi knockdown, qRT-PCR/western blot RNA High 19383765
2010 DGCR8 binds pri-miRNAs with high cooperativity through the formation of higher-order structures (a trimer of DGCR8 dimers) on the pri-miRNA; the amphipathic C-terminal helix of DGCR8 is important for trimerization on pri-miRNAs and for Drosha-mediated cleavage; electron tomography 3D modeling supports this trimeric assembly. Biochemical binding assays, in vitro cleavage assay, electron tomography, mutational analysis RNA High 20558544
2011 DGCR8 forms a highly stable complex with ferric [Fe(III)] heme using two endogenous cysteine side chains as axial ligands, making it the first known heme protein with a double-cysteine ligation; this heme complex is required for DGCR8 pri-miRNA processing activity. Biochemical characterization, electronic absorption spectroscopy, magnetic circular dichroism, electron paramagnetic resonance, selenomethionine substitution, mercury titration, in vitro processing assay Journal of Biological Chemistry High 21454614
2012 Ferric [Fe(III)] heme activates DGCR8 for pri-miRNA processing; reduction of heme iron to the ferrous [Fe(II)] state abolishes processing activity by causing loss of cysteine axial ligands and dramatic increase in heme dissociation rate; apoDGCR8 dimers generated by heme removal show low processing activity restored by ferric but not ferrous heme. In vitro processing assay, electronic absorption spectroscopy, magnetic circular dichroism, resonance Raman spectroscopy, heme reconstitution Proceedings of the National Academy of Sciences High 22308374
2012 DGCR8 HITS-CLIP reveals that DGCR8 binds not only miRNA precursors but also hundreds of mRNAs, snoRNAs, and long noncoding RNAs (including MALAT1); DGCR8 controls mRNA and MALAT1 abundance; DGCR8 cleaves snoRNAs independently of Drosha, suggesting participation in complexes with other endonucleases; DGCR8 binding to cassette exons regulates alternative splicing isoform abundance. HITS-CLIP, deep sequencing, knockdown experiments, RNA abundance measurement Nature structural & molecular biology High 22796965
2012 HDAC1 is an integral component of the Drosha/DGCR8 complex and enhances miRNA processing by deacetylating critical lysine residues in the RNA-binding domains of DGCR8, thereby increasing DGCR8 affinity for primary miRNA transcripts. Co-immunoprecipitation, in vitro deacetylation assay, RNA-binding assay, miRNA expression profiling EMBO reports High 22222205
2012 Dimerization and heme binding are evolutionarily conserved properties of DGCR8; the crystal structure of the Xenopus laevis DGCR8 dimerization domain closely resembles that of human DGCR8; dimerization creates a surface important for heme association. X-ray crystallography, spectroscopic heme-binding assay PloS one Medium 22768307
2013 Expanded CGG RNA repeats (associated with FXTAS) sequester DGCR8 and its partner DROSHA within nuclear RNA aggregates, partially depleting the Microprocessor and reducing mature miRNA levels in neuronal cells and patient brain tissue; overexpression of DGCR8 rescues neuronal cell death caused by expanded CGG repeats. RNA immunoprecipitation, RNA FISH, miRNA profiling, DGCR8 overexpression rescue assay in neuronal cells Cell reports High 23478018
2013 DGCR8 phosphorylation by mitogenic ERK/MAPK signaling increases DGCR8 protein stability (not via mRNA, localization changes, or self-association); phosphomimetic DGCR8 leads to a pro-growth miRNA expression profile and increased cell proliferation; 23 phosphorylation sites on full-length human DGCR8 were mapped by phosphoproteomics. Phosphoproteomics mapping, phosphomimetic/phosphomutant DGCR8 expression, western blot, miRNA profiling, proliferation/scratch assay Cell reports High 24239349
2014 MeCP2 directly binds DGCR8 and interferes with assembly of the Drosha-DGCR8 complex, thereby suppressing nuclear miRNA processing; MeCP2-dependent inhibition of miRNA processing regulates dendritic and spine growth, and gain-of-function MeCP2's inhibition of dendritic growth depends on its interaction with DGCR8. Co-immunoprecipitation, in vitro processing assay, confocal imaging, neuronal morphology analysis with DGCR8-interaction-deficient MeCP2 mutants Developmental cell High 24636259
2014 The DGCR8 RNA-binding heme domain (Rhed, dimeric) directly contacts pri-miRNA hairpins; two DGCR8 dimers bind each pri-miRNA hairpin using their Rheds, with binding sites at both ends of the hairpin; the heme cofactor is required for formation of processing-competent DGCR8-pri-miRNA complexes; the Rhed RNA-binding surface is important for pri-miRNA processing activity. In vitro RNA-binding assay, in vitro processing assay, heme-domain mutant analysis, stoichiometry analysis Cell reports High 24910438
2015 DGCR8 acts as an adaptor to recruit the nuclear exosome (preferentially its hRRP6-containing nucleolar form) to structured RNAs including snoRNAs and telomerase RNA (hTR/TERC), independently of Drosha; DGCR8 copurifies with exosome subunits and is essential for exosome recruitment to these substrates. Co-purification, co-immunoprecipitation, RNAi knockdown, RNA abundance measurement, snoRNA/hTR processing assays Molecular cell High 26687677
2015 DGCR8 is SUMOylated at K707 (the major site) by SUMO1, a modification promoted by ERK-activated phosphorylation; SUMOylation enhances DGCR8 protein stability by preventing ubiquitin-proteasome degradation; SUMOylation does not alter DGCR8 association with Drosha or Microprocessor cleavage activity, but alters DGCR8 affinity for pri-miRNAs and influences direct pri-miRNA functions in gene silencing. Site-directed mutagenesis, SUMOylation assay, ubiquitination assay, Co-IP, RNA-binding assay, in vitro processing assay, cell migration/invasion assay Nucleic acids research High 26202964
2015 The ABL tyrosine kinase phosphorylates DGCR8 at Tyr267 in response to DNA damage; this phosphorylation is required for ABL-stimulated processing of select pri-miRNAs (e.g., pri-miR-34c but not pri-miR-34a); phosphorylation of DGCR8 Y267 alters DGCR8 association with the pri-miRNA and facilitates Drosha recruitment. In vitro kinase assay, co-immunoprecipitation, RNA cross-linking assay, Y267F mutant rescue experiment, miRNA expression in ABL nuclear import-defective mice Science signaling High 26126715
2017 Heme is critical for Microprocessor to process pri-miRNAs with high fidelity; heme-bound DGCR8 corrects erroneous Drosha binding; heme induces a conformational change in DGCR8 (rather than changing oligomerization state); heme activates DGCR8 to recognize pri-miRNAs by specifically binding the terminal loop near the 3' single-stranded segment. In vitro processing assay with heme manipulation, conformational analysis, biochemical binding assays Nature communications High 29170488
2017 DGCR8 has a miRNA-processing-independent role in maintaining heterochromatin organization by interacting with the nuclear envelope protein Lamin B1 and heterochromatin-associated proteins KAP1 and HP1γ; loss of this function (via N-terminal-truncated DR8dex2) accelerates senescence in human mesenchymal stem cells; DGCR8 overexpression reverses premature senescent phenotypes. Co-immunoprecipitation, senescence assays, overexpression/knockdown experiments in hMSCs, mouse osteoarthritis model Nature communications High 31350386
2017 DGCR8 has a Drosha-independent role in facilitating alternative splicing of Tcf7l1 mRNA; DGCR8 directly interacts with Tcf7l1 mRNA as shown by RNA immunoprecipitation; a phosphomutant DGCR8 that restores miRNA levels fails to rescue exit from pluripotency defect, demonstrating a noncanonical splicing function. RNA immunoprecipitation, RNA-seq, phosphomutant DGCR8 complementation in Dgcr8-knockout mESCs Journal of cell biology High 28100686
2017 UV irradiation induces JNK-mediated phosphorylation of DGCR8 at serine 153; this phosphorylation is critical for cellular UV resistance and removal of UV-induced DNA lesions via transcription-coupled nucleotide excision repair (TC-NER), independently of miRNA expression or Drosha-binding activity; DGCR8 physically interacts with CSB and RNA polymerase II; DGCR8 depletion is epistatic to XPA, CSA, and CSB defects for UV sensitivity. Phosphorylation mapping, S153A mutant analysis, epistasis analysis with NER factors, Co-IP with CSB and RNA Pol II, UV lesion removal assay, miRNA expression analysis Cell reports High 28380355
2020 Cryo-EM structure of human Microprocessor (Drosha-DGCR8) with pri-miRNA reveals: the basal junction is recognized by a four-way intramolecular junction in Drosha with Belt and Wedge regions clamping ssRNA; two DGCR8 dsRBDs form a molecular ruler to measure stem length between the two dsRNA-ssRNA junctions; the apical junction DGCR8 dsRBD organization is independent of Drosha core domains (observed in a partially docked state structure). Cryo-electron microscopy structural determination, functional mutagenesis of Belt and Wedge regions Molecular cell High 32220646
2020 Amino acids 461-463 in the Rhed (RNA-binding heme domain, residues 285-478) of DGCR8 are critical for interaction with the apical UGU motif of pri-miRNAs and are essential for accurate and efficient processing of UGU-pri-miRNAs in vitro; within the DGCR8 dimer, residues 461-463 from one monomer discriminate between UGU and non-UGU pri-miRNAs. Site-directed mutagenesis, in vitro processing assay, RNA-binding assay, cellular miRNA expression analysis Communications biology High 32620823
2020 METTL3-mediated m6A modification promotes pri-miRNA processing in a DGCR8-dependent manner; METTL3 overexpression increases mature miRNA levels through DGCR8-dependent Microprocessor activity, as DGCR8 knockdown abrogates the effect of METTL3 on miRNA maturation. RNAi knockdown of DGCR8, miRNA expression analysis, METTL3 overexpression Aging Medium 32365051
2020 ERH (Enhancer of Rudimentary Homolog) is a new component of the Microprocessor; crystal structure reveals ERH uses its hydrophobic groove to bind a conserved N-terminal region of DGCR8 in a 2:2 stoichiometry; ERH knockdown or deletion of the DGCR8 N-terminus reduces processing of suboptimal pri-miRNAs in polycistronic clusters; ERH mediates 'cluster assistance' for poor substrates via neighboring high-affinity substrates. X-ray crystallography, biochemical binding assay, knockdown of ERH, in vitro processing assay, cellular miRNA expression analysis Nucleic acids research High 33035348
2021 DGCR8 promotes tumor resistance to X-ray radiation independently of Drosha-binding; upon radiation, ATM phosphorylates DGCR8 at serine 677, which facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8; stabilized DGCR8 recruits RNF168 to MDC1 and RNF8 at DSBs, promoting H2A ubiquitination and DSB repair. Kinase assay (ATM), deubiquitination assay (USP51), co-immunoprecipitation, site-specific mutant (S677A), H2A ubiquitination assay, radioresistance assay Nature communications High 34188037
2021 USP36 associates with the Microprocessor complex, interacts with DGCR8, and promotes DGCR8 SUMOylation specifically by SUMO2; USP36-mediated SUMOylation does not affect DGCR8 protein levels or Drosha-DGCR8 complex formation but promotes DGCR8 binding to pri-miRNAs; USP36 knockdown reduces pri-miRNA processing and mature miRNA levels; SUMOylation-defective DGCR8 mutant inhibits cell proliferation. Co-immunoprecipitation, in vitro SUMOylation assay, RNA-binding assay, pri-miRNA processing assay, miRNA expression analysis, site-specific mutant Cancer research communications High 36950067
2021 Coilin (Cajal body marker protein) directly forms a complex with DGCR8 as shown by co-immunoprecipitation; coilin knockdown reduces DGCR8 phosphorylation and protein stability, alters levels of primary and mature miRNAs and their targets, implicating coilin in the regulatory network governing Microprocessor activity. Co-immunoprecipitation, coilin knockdown, western blot, miRNA expression analysis Molecular biology of the cell Medium 34319763
2023 DGCR8 has a non-canonical function in mRNA subcellular localization; CCDC137 binds DGCR8, and DGCR8 mediates the cytoplasmic distribution of CCDC137-bound mRNAs (FOXM1, JTV1, LASP1, FLOT2), thereby enhancing their protein expression and activating AKT signaling in hepatocellular carcinoma. Co-immunoprecipitation, APOBEC1-based mRNA profiling, subcellular fractionation, functional knockdown/overexpression Journal of experimental & clinical cancer research Medium 37542342

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The Drosha-DGCR8 complex in primary microRNA processing. Genes & development 1645 15574589
2006 Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 1132 16751099
2007 DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nature genetics 791 17259983
2009 Posttranscriptional crossregulation between Drosha and DGCR8. Cell 347 19135890
2015 Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors. Cancer cell 242 25670083
2015 Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors. Cancer cell 227 25670082
2011 Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)--a new autoinflammatory syndrome distinct from PAPA syndrome. Journal of the American Academy of Dermatology 220 21745697
2014 MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex. Developmental cell 205 24636259
2006 Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing. Nucleic acids research 205 16963499
2013 Sequestration of DROSHA and DGCR8 by expanded CGG RNA repeats alters microRNA processing in fragile X-associated tremor/ataxia syndrome. Cell reports 201 23478018
2012 DGCR8 HITS-CLIP reveals novel functions for the Microprocessor. Nature structural & molecular biology 179 22796965
2011 Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex. Proceedings of the National Academy of Sciences of the United States of America 172 21368174
2013 Reduced adult hippocampal neurogenesis and working memory deficits in the Dgcr8-deficient mouse model of 22q11.2 deletion-associated schizophrenia can be rescued by IGF2. The Journal of neuroscience : the official journal of the Society for Neuroscience 132 23719809
2020 Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8. Aging 126 32365051
2009 Post-transcriptional control of DGCR8 expression by the Microprocessor. RNA (New York, N.Y.) 115 19383765
2019 Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis. Nature communications 106 31350386
2003 Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region. Biochemical and biophysical research communications 103 12705904
2020 Cryo-EM Structures of Human Drosha and DGCR8 in Complex with Primary MicroRNA. Molecular cell 100 32220646
2009 Genome-wide identification of targets of the drosha-pasha/DGCR8 complex. RNA (New York, N.Y.) 95 19223442
2011 A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing. RNA (New York, N.Y.) 94 21712401
2018 Noncanonical functions of microRNA pathway enzymes - Drosha, DGCR8, Dicer and Ago proteins. FEBS letters 92 30025156
2007 Nucleolar localization of DGCR8 and identification of eleven DGCR8-associated proteins. Experimental cell research 91 17765891
2007 Crystal structure of human DGCR8 core. Nature structural & molecular biology 89 17704815
2012 Ferric, not ferrous, heme activates RNA-binding protein DGCR8 for primary microRNA processing. Proceedings of the National Academy of Sciences of the United States of America 79 22308374
2013 Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile. Cell reports 75 24239349
2014 Germ cell-specific targeting of DICER or DGCR8 reveals a novel role for endo-siRNAs in the progression of mammalian spermatogenesis and male fertility. PloS one 74 25244517
2011 Monoallelic deletion of the microRNA biogenesis gene Dgcr8 produces deficits in the development of excitatory synaptic transmission in the prefrontal cortex. Neural development 73 21466685
2014 The DGCR8 RNA-binding heme domain recognizes primary microRNAs by clamping the hairpin. Cell reports 69 24910438
2015 DGCR8 Acts as an Adaptor for the Exosome Complex to Degrade Double-Stranded Structured RNAs. Molecular cell 66 26687677
2014 Induced multipotency in adult keratinocytes through down-regulation of ΔNp63 or DGCR8. Proceedings of the National Academy of Sciences of the United States of America 66 24449888
2012 Histone deacetylase 1 enhances microRNA processing via deacetylation of DGCR8. EMBO reports 66 22222205
2014 Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PloS one 65 25084529
2017 Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs. Nature communications 58 29170488
2020 DGCR8 microprocessor defect characterizes familial multinodular goiter with schwannomatosis. The Journal of clinical investigation 53 31805011
2011 DiGeorge critical region 8 (DGCR8) is a double-cysteine-ligated heme protein. The Journal of biological chemistry 53 21454614
2010 DGCR8 recognizes primary transcripts of microRNAs through highly cooperative binding and formation of higher-order structures. RNA (New York, N.Y.) 52 20558544
2012 DiGeorge syndrome critical region 8 (DGCR8) protein-mediated microRNA biogenesis is essential for vascular smooth muscle cell development in mice. The Journal of biological chemistry 51 22511778
2011 Dgcr8 controls neural crest cells survival in cardiovascular development. Developmental biology 49 22138056
2008 A Drosophila pasha mutant distinguishes the canonical microRNA and mirtron pathways. Molecular and cellular biology 45 19047376
2009 Genomic analysis suggests that mRNA destabilization by the microprocessor is specialized for the auto-regulation of Dgcr8. PloS one 43 19759829
2017 MicroRNA-independent functions of DGCR8 are essential for neocortical development and TBR1 expression. EMBO reports 42 28232627
2019 Biodegradation of decabromodiphenyl ether (BDE-209) using a novel microbial consortium GY1: Cells viability, pathway, toxicity assessment, and microbial function prediction. The Science of the total environment 41 31018474
2015 SUMOylation at K707 of DGCR8 controls direct function of primary microRNA. Nucleic acids research 39 26202964
2015 Dgcr8 and Dicer are essential for sex chromosome integrity during meiosis in males. Journal of cell science 38 25934699
2019 Dgcr8 knockout approaches to understand microRNA functions in vitro and in vivo. Cellular and molecular life sciences : CMLS 37 30694346
2021 METTL3 improves cardiomyocyte proliferation upon myocardial infarction via upregulating miR-17-3p in a DGCR8-dependent manner. Cell death discovery 34 34645805
2014 Drosha-independent DGCR8/Pasha pathway regulates neuronal morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 34 24474768
2013 The core microprocessor component DiGeorge syndrome critical region 8 (DGCR8) is a nonspecific RNA-binding protein. The Journal of biological chemistry 34 23893406
2017 DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing. Cell reports 32 28380355
2016 ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer. Cancer cell 32 27300436
2016 MicroRNA-dependent roles of Drosha and Pasha in the Drosophila larval ovary morphogenesis. Developmental biology 32 27339292
2021 Whole-genome Sequencing of Follicular Thyroid Carcinomas Reveal Recurrent Mutations in MicroRNA Processing Subunit DGCR8. The Journal of clinical endocrinology and metabolism 31 34171097
2020 ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8. Nucleic acids research 31 33035348
2017 Noncanonical function of DGCR8 controls mESC exit from pluripotency. The Journal of cell biology 31 28100686
2015 Silencing the double-stranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion. Pharmaceutical research 31 25823356
2015 Microprocessor complex subunit DiGeorge syndrome critical region gene 8 (Dgcr8) is required for schwann cell myelination and myelin maintenance. The Journal of biological chemistry 30 26272614
2013 An essential microRNA maturing microprocessor complex component DGCR8 is up-regulated in colorectal carcinomas. Clinical and experimental medicine 30 23775303
2010 Regulation of the microRNA processor DGCR8 by the tumor suppressor ING1. Cancer research 30 20179197
2009 The male-determining gene SRY is a hybrid of DGCR8 and SOX3, and is regulated by the transcription factor CP2. Molecular and cellular biochemistry 30 19902333
2021 Non-canonical function of DGCR8 in DNA double-strand break repair signaling and tumor radioresistance. Nature communications 29 34188037
2012 Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells. Biochemical and biophysical research communications 27 22925886
2020 Select amino acids in DGCR8 are essential for the UGU-pri-miRNA interaction and processing. Communications biology 26 32620823
2014 Expression of DGCR8-dependent microRNAs is indispensable for osteoclastic development and bone-resorbing activity. Journal of cellular biochemistry 26 24420069
2010 Short interfering RNA-mediated knockdown of drosha and pasha in undifferentiated Meloidogyne incognita eggs leads to irregular growth and embryonic lethality. International journal for parasitology 26 20398669
2019 DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells. Molecular therapy : the journal of the American Society of Gene Therapy 25 31813799
2017 BRG1 and SMARCAL1 transcriptionally co-regulate DROSHA, DGCR8 and DICER in response to doxorubicin-induced DNA damage. Biochimica et biophysica acta. Gene regulatory mechanisms 25 28716689
2016 The microprocessor component, DGCR8, is essential for early B-cell development in mice. European journal of immunology 25 27641147
2013 DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts. Aging cell 23 23773483
2022 METTL3 contributes to slow transit constipation by regulating miR-30b-5p/PIK3R2/Akt/mTOR signaling cascade through DGCR8. Journal of gastroenterology and hepatology 20 36068012
2016 Drosha, DGCR8, and Dicer mRNAs are down-regulated in human cells infected with dengue virus 4, and play a role in viral pathogenesis. Genetics and molecular research : GMR 20 27173348
2015 Loss of Dgcr8-mediated microRNA expression in the kidney results in hydronephrosis and renal malformation. BMC nephrology 20 25881298
2013 DGCR8-mediated production of canonical microRNAs is critical for regulatory T cell function and stability. PloS one 20 23741528
2020 Deficient Expression of DGCR8 in Human Testis is Related to Spermatogenesis Dysfunction, Especially in Meiosis I. International journal of general medicine 19 32523370
2017 Deletion Extents Are Not the Cause of Clinical Variability in 22q11.2 Deletion Syndrome: Does the Interaction between DGCR8 and miRNA-CNVs Play a Major Role? Frontiers in genetics 19 28507561
2017 A DGCR8-Independent Stable MicroRNA Expression Strategy Reveals Important Functions of miR-290 and miR-183-182 Families in Mouse Embryonic Stem Cells. Stem cell reports 19 28988987
2014 Overexpression of microRNA biogenesis machinery: Drosha, DGCR8 and Dicer in multiple sclerosis patients. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 19 25439752
2019 Dysregulation of the miRNA biogenesis components DICER1, DROSHA, DGCR8 and AGO2 in clear cell renal cell carcinoma in both a Korean cohort and the cancer genome atlas kidney clear cell carcinoma cohort. Oncology letters 18 31516620
2017 Deficiency of DGCR8 increases bone formation through downregulation of miR-22 expression. Bone 18 28739418
2016 Deficiency in DGCR8-dependent canonical microRNAs causes infertility due to multiple abnormalities during uterine development in mice. Scientific reports 18 26833131
2012 Dimerization and heme binding are conserved in amphibian and starfish homologues of the microRNA processing protein DGCR8. PloS one 18 22768307
2011 Isolation and characterization of cDNAs encoding Ars2 and Pasha homologues, two components of the RNA interference pathway in Litopenaeus vannamei. Fish & shellfish immunology 18 22155278
2023 RNA-binding protein CCDC137 activates AKT signaling and promotes hepatocellular carcinoma through a novel non-canonical role of DGCR8 in mRNA localization. Journal of experimental & clinical cancer research : CR 17 37542342
2021 DGCR8-dependent efficient pri-miRNA processing of human pri-miR-9-2. The Journal of biological chemistry 16 33581109
2019 Long noncoding RNA SNHG14 enhances migration and invasion of ovarian cancer by upregulating DGCR8. European review for medical and pharmacological sciences 16 31841176
2018 Dgcr8 deletion in the primitive heart uncovered novel microRNA regulating the balance of cardiac-vascular gene program. Protein & cell 16 30128894
2015 The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage. Science signaling 16 26126715
2024 Prevalence, Molecular Landscape, and Clinical Impact of DICER1 and DGCR8 Mutated Follicular-Patterned Thyroid Nodules. The Journal of clinical endocrinology and metabolism 15 38252873
2017 Germline-specific dgcr8 knockout in zebrafish using a BACK approach. Cellular and molecular life sciences : CMLS 15 28224202
2014 Regulation of the microRNA processor DGCR8 by hepatitis B virus proteins via the transcription factor YY1. Archives of virology 15 25427980
2020 DGCR8/miR-106 Axis Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinomas by Downregulating RUNX3. Frontiers in medicine 13 33385002
2023 Co-cultivation effects of Lactobacillus helveticus SNA12 and Kluveromyces marxiensis GY1 on the probiotic properties, flavor, and digestion in fermented milk. Food research international (Ottawa, Ont.) 12 37254417
2021 Coilin enhances phosphorylation and stability of DGCR8 and promotes miRNA biogenesis. Molecular biology of the cell 12 34319763
2010 MD simulations of the dsRBP DGCR8 reveal correlated motions that may aid pri-miRNA binding. Biophysical journal 12 20655853
2023 The Ubiquitin-specific Protease USP36 Associates with the Microprocessor Complex and Regulates miRNA Biogenesis by SUMOylating DGCR8. Cancer research communications 11 36950067
2020 Circ PSMC3 inhibits prostate cancer cell proliferation by downregulating DGCR8. European review for medical and pharmacological sciences 11 32196577
2020 STAT5A induced LINC01198 promotes proliferation of glioma cells through stabilizing DGCR8. Aging 11 32246817
2019 Long noncoding RNA TUG1 promotes progression via upregulating DGCR8 in prostate cancer. European review for medical and pharmacological sciences 11 30964164
2021 CCR1 enhances SUMOylation of DGCR8 by up-regulating ERK phosphorylation to promote spinal nerve ligation-induced neuropathic pain. Gene therapy 10 34413501
2016 Upregulation of the double-stranded RNA binding protein DGCR8 in invasive ductal breast carcinoma. Gene 10 26804549
2012 Large-scale identification of microRNA targets in murine Dgcr8-deficient embryonic stem cell lines. PloS one 10 22912678