Affinage

DGCR8

Microprocessor complex subunit DGCR8 · UniProt Q8WYQ5

Length
773 aa
Mass
86.0 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DGCR8 is the obligate double-stranded RNA-binding partner of Drosha within the nuclear Microprocessor complex that initiates microRNA biogenesis by cleaving primary miRNA transcripts (PMID:15574589, PMID:17259983). DGCR8, but not Drosha, directly and specifically binds pri-miRNAs through its tandem dsRBDs, recognizing the flanking single-stranded segments and acting as a molecular anchor that measures ~11 bp from the dsRNA-ssRNA junction to position Drosha's catalytic cleavage (PMID:16751099, PMID:16963499); the cryo-EM structure of the assembled complex shows the two dsRBDs forming a molecular ruler across the stem while Drosha recognizes the basal junction (PMID:32220646). Beyond its dsRBDs, DGCR8 carries an RNA-binding heme domain (Rhed) that binds ferric [Fe(III)] heme via two endogenous cysteine axial ligands and contacts the apical UGU motif of pri-miRNAs, with ferric heme activating processing-competent complex formation and conferring cleavage fidelity (PMID:21454614, PMID:24910438, PMID:29170488, PMID:32620823). Substrate discrimination is enhanced by cooperative higher-order DGCR8 assembly on pri-miRNAs (PMID:20558544) and by the accessory subunit ERH, which binds the DGCR8 N-terminus to enable processing of suboptimal clustered pri-miRNAs (PMID:33035348). Microprocessor autoregulates the pathway by cleaving hairpins in DGCR8 mRNA while DGCR8 reciprocally stabilizes Drosha protein, forming a homeostatic feedback loop (PMID:19135890, PMID:19383765). DGCR8 activity and stability are tuned by extensive post-translational regulation, including ERK phosphorylation and SUMOylation that stabilize the protein and modulate pri-miRNA affinity (PMID:24239349, PMID:26202964, PMID:36950067), HDAC1-mediated deacetylation that raises RNA-binding affinity (PMID:22222205), and ABL-dependent Y267 phosphorylation that selectively drives DNA-damage-induced miRNA processing (PMID:26126715). DGCR8 also performs Drosha-independent, miRNA-independent functions: it serves as an adaptor recruiting the nuclear exosome to snoRNAs and telomerase RNA to control their stability (PMID:26687677), contributes to transcription-coupled nucleotide excision repair through JNK-mediated S153 phosphorylation and interaction with CSB and RNA Pol II (PMID:28380355), promotes double-strand break repair via ATM/USP51-controlled S677 phosphorylation and RNF168 recruitment (PMID:34188037), maintains heterochromatin organization through Lamin B1, KAP1, and HP1γ (PMID:31350386), and facilitates Tcf7l1 mRNA splicing required for stem-cell differentiation (PMID:28100686). Genetically, DGCR8 is essential for miRNA production and embryonic stem cell differentiation, with knockout cells failing to silence pluripotency upon differentiation (PMID:17259983).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2004 High

    Established that pri-miRNA processing requires a dedicated multiprotein complex, identifying DGCR8 as an essential dsRNA-binding cofactor of the Drosha nuclease.

    Evidence RNAi knockdown, biochemical reconstitution, and Drosha active-site mutagenesis of the ~650 kDa Microprocessor

    PMID:15574589

    Open questions at the time
    • Did not resolve which subunit recognizes substrate
    • No structural basis for cleavage positioning
  2. 2006 High

    Resolved the division of labor within Microprocessor by showing DGCR8 is the substrate-recognition subunit that anchors and measures the pri-miRNA to set the cleavage site.

    Evidence Purified-protein EMSA binding, pri-miRNA mutational analysis, and domain mapping with reciprocal co-IP

    PMID:16751099 PMID:16963499

    Open questions at the time
    • Atomic structure of the recognition surface not yet determined
    • Mechanism of distance measurement inferred, not visualized
  3. 2007 High

    Provided structural and genetic foundations: the dsRBD core fold for substrate recognition and the genetic requirement of DGCR8 for miRNA-dependent pluripotency exit.

    Evidence X-ray crystallography of the DGCR8 core with FRET, plus conditional Dgcr8-knockout mouse ES cells

    PMID:17259983 PMID:17704815

    Open questions at the time
    • Orientation of binding ambiguous from crystal alone
    • Subnuclear localization determinants partially defined
  4. 2009 High

    Defined homeostatic control of the pathway, showing Microprocessor cleaves DGCR8 mRNA hairpins while DGCR8 stabilizes Drosha, establishing reciprocal cross-regulation.

    Evidence In vitro cleavage reconstitution, Drosha knockdown, and luciferase reporter assays of the DGCR8 5'UTR hairpin

    PMID:19135890 PMID:19383765

    Open questions at the time
    • Physiological triggers that tip the feedback balance not defined
    • Quantitative set-point of the loop unknown
  5. 2010 High

    Explained substrate selectivity through cooperative higher-order DGCR8 assembly that distinguishes pri-miRNAs from nonspecific RNAs.

    Evidence EMSA, gel filtration, in vitro processing, electron tomography, and C-terminal helix mutagenesis

    PMID:20558544

    Open questions at the time
    • Stoichiometry in the cleavage-competent complex later revised
    • In-cell relevance of trimer model not directly tested
  6. 2011 High

    Discovered DGCR8 as a heme-binding protein using two cysteine axial ligands, identifying an unexpected cofactor in miRNA biogenesis.

    Evidence UV-vis, MCD, EPR spectroscopy with cysteine/P351A mutagenesis and eukaryotic expression

    PMID:21454614

    Open questions at the time
    • Functional role of heme in processing not yet shown
    • Redox-state dependence undefined at this stage
  7. 2012 High

    Established ferric heme as an activator of pri-miRNA processing and demonstrated DGCR8's RNA targets, heme conservation, and HDAC1-dependent activation extend beyond canonical miRNA biology.

    Evidence In vitro processing with heme redox manipulation; HITS-CLIP transcriptome mapping; Xenopus/starfish heme assays; HDAC1 co-IP and deacetylation assays

    PMID:22222205 PMID:22308374 PMID:22768307 PMID:22796965

    Open questions at the time
    • Source and dynamics of cellular heme loading unknown
    • Drosha-independent endonuclease partner for snoRNA cleavage unidentified
  8. 2013 Medium

    Linked DGCR8 to disease by showing expanded CGG repeats sequester DGCR8/Drosha and reduce miRNA processing, with DGCR8 overexpression rescuing toxicity.

    Evidence RNA-protein binding, co-localization imaging, miRNA profiling in patient tissue, and DGCR8 rescue

    PMID:23478018

    Open questions at the time
    • Single disease model
    • Quantitative contribution of sequestration to pathology unclear
  9. 2014 Medium

    Demonstrated post-translational and protein-interaction control of Microprocessor: ERK phosphorylation stabilizes DGCR8 toward a pro-growth profile, while MeCP2 binding blocks complex assembly.

    Evidence Phosphoproteomics with phosphomimetic mutants and stability assays; MeCP2-DGCR8 co-IP with neuronal morphology readouts

    PMID:24239349 PMID:24636259

    Open questions at the time
    • Functional kinase(s) in vivo for individual sites not all defined
    • MeCP2 interaction studied in a single lab
  10. 2014 Medium

    Revealed the Rhed heme domain directly contacts pri-miRNAs and that heme is required to form processing-competent complexes, integrating the cofactor into substrate recognition.

    Evidence RNA binding and processing assays with Rhed deletion/mutant constructs and oligomeric-state analysis

    PMID:24910438

    Open questions at the time
    • Precise heme-induced conformational change not yet resolved
    • Single-lab biochemistry
  11. 2015 Medium

    Expanded DGCR8 into Drosha-independent and post-translational regulatory roles: nuclear exosome adaptor for structured ncRNAs, SUMO/ABL-controlled stability and selective processing.

    Evidence Exosome co-purification with snoRNA/hTR stability assays; K707 SUMOylation mutagenesis; ABL kinase and Y267F functional analysis

    PMID:26126715 PMID:26202964 PMID:26687677

    Open questions at the time
    • How DGCR8 switches between Drosha and exosome partners unknown
    • In vivo significance of selective miRNA induction limited to subset
  12. 2017 High

    Defined two independent genome-protective roles for DGCR8 in DNA repair: JNK/S153-driven transcription-coupled NER and a heme-dependent fidelity mechanism in processing.

    Evidence S153 phosphomutant with NER epistasis and CSB/RNAPII co-IP; in vitro fidelity and conformational assays with heme

    PMID:28380355 PMID:29170488

    Open questions at the time
    • Mechanism by which DGCR8 acts within TC-NER not fully resolved
    • Structural basis of heme-driven fidelity not visualized
  13. 2017 Medium

    Identified miRNA-independent roles in heterochromatin maintenance and stem-cell mRNA splicing, separating canonical from non-canonical DGCR8 functions genetically.

    Evidence Lamin B1/KAP1/HP1γ co-IP with truncation mutants and senescence assays; Tcf7l1 RIP with phosphomutant complementation in mESCs

    PMID:28100686 PMID:31350386

    Open questions at the time
    • Direct molecular mechanism of heterochromatin stabilization unclear
    • Generality of splicing role beyond Tcf7l1 untested
  14. 2019 Medium

    Extended the heterochromatin-stabilizing function to therapeutic relevance in stem-cell aging and osteoarthritis.

    Evidence Co-IP plus hMSC aging and mouse osteoarthritis models with DGCR8 overexpression

    PMID:31350386

    Open questions at the time
    • Same study as the mechanistic finding
    • Causal chain from DGCR8 to disease phenotype not fully dissected
  15. 2020 High

    Provided the structural basis for substrate recognition and refined accessory-factor and Rhed-motif contributions to processing accuracy.

    Evidence Cryo-EM of Drosha-DGCR8 with docked pri-miRNA; Rhed 461–463 mutagenesis for UGU recognition; ERH-DGCR8 crystal structure with cluster-assistance assays

    PMID:32220646 PMID:32620823 PMID:33035348

    Open questions at the time
    • Dynamics of substrate loading not captured in static structure
    • How heme-dependent and structural mechanisms integrate at atomic level open
  16. 2021 High

    Connected DGCR8 to double-strand break repair and further refined its regulatory modifications and partners.

    Evidence ATM/S677 and USP51-dependent stabilization with RNF168 recruitment and DSB foci assays; USP36-driven SUMO2ylation; coilin co-IP and knockdown

    PMID:34188037 PMID:34319763 PMID:36950067

    Open questions at the time
    • Coilin interaction rests on single low-confidence co-IP with indirect readouts
    • Interplay among the multiple competing ubiquitin/SUMO modifiers unresolved
  17. 2023 Low

    Proposed a non-canonical role for DGCR8 in cytoplasmic mRNA localization via CCDC137 in hepatocellular carcinoma.

    Evidence CCDC137-DGCR8 co-IP, C-BERST mRNA profiling, and subcellular fractionation with knockdown

    PMID:37542342

    Open questions at the time
    • Single co-IP and fractionation without orthogonal validation
    • Direct versus indirect mRNA contact undetermined
    • Mechanism of cytoplasmic export by a nuclear protein unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DGCR8 is partitioned among its many competing complexes (Microprocessor, exosome, repair, heterochromatin) and how the cell coordinates its heme loading, phosphorylation, SUMOylation, and ubiquitination to select among these functions remains unresolved.
  • No integrated model of partner selection
  • Stoichiometry and regulation of non-canonical complexes in vivo unknown
  • Spatiotemporal control of competing post-translational modifications undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0008289 lipid binding 4 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
DROSHAERHHDAC1KAP1LAMIN B1MECP2USP36USP51
Complex memberships
Microprocessor (Drosha-DGCR8)nuclear exosome (hRRP6-containing)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 DGCR8 is an essential component of the ~650 kDa Drosha complex (Microprocessor) required for pri-miRNA processing. Drosha's two RNase III domains form an intramolecular dimer to cleave the 3' and 5' strands of the pri-miRNA stem. DGCR8, containing two dsRNA-binding domains, was shown by RNAi knockdown and biochemical reconstitution to be required for pri-miRNA processing activity. RNAi knockdown, biochemical reconstitution, size-exclusion fractionation, co-immunoprecipitation, active-site mutagenesis of Drosha RNase III domains 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 that measures the distance (~11 bp) from the dsRNA-ssRNA junction to determine the Drosha cleavage site. Purified protein binding assays (EMSA), pri-miRNA mutational analysis, computational modeling Cell High 16751099
2006 The tandem dsRNA-binding domains (dsRBDs) of DGCR8 are responsible for direct and stable interaction with pri-miRNAs. Drosha is stabilized through an interaction between its middle domain and the conserved C-terminal domain of DGCR8. The DGCR8 N-terminal region is unnecessary for pri-miRNA processing but is critical for nuclear localization. Domain deletion/mutant constructs, co-immunoprecipitation, RNA binding assays, subcellular localization imaging Nucleic acids research High 16963499
2007 DGCR8 is essential for microRNA biogenesis in mouse embryonic stem cells. Dgcr8 knockout ES cells fail to produce mature miRNAs and do not fully silence pluripotency markers upon induction of differentiation, establishing DGCR8's role in ES cell self-renewal silencing. Conditional Dgcr8 knockout mouse ES cells, Northern blot for miRNA levels, pluripotency marker expression analysis Nature genetics High 17259983
2007 Crystal structure of the human DGCR8 core (residues 493–720) revealed that the two dsRBDs are arranged with pseudo two-fold symmetry tightly packed against a C-terminal helix. The H2 helix in each dsRBD is important for pri-miRNA substrate recognition. FRET and mutational analyses suggest the DGCR8 core can recognize pri-miRNA in two possible orientations. X-ray crystallography, FRET, mutational analysis of dsRBD residues Nature structural & molecular biology High 17704815
2007 DGCR8 localizes to the nucleolus and small foci adjacent to splicing speckles in the nucleoplasm. Nucleolar localization of DGCR8 changes upon inhibition of RNA transcription. DGCR8 associates with at least four distinct protein complexes: DROSHA/DGCR8, DGCR8/Nucleolin (RNA-dependent), DGCR8/ILF3, and ILF3/XPO5. Immunoprecipitation/mass spectrometry, co-immunoprecipitation, immunofluorescence microscopy, immunoelectron microscopy, RNA transcription inhibition Experimental cell research Medium 17765891
2009 The Drosha-DGCR8 complex (Microprocessor) cleaves hairpin structures embedded in the DGCR8 mRNA 5'UTR and coding region, destabilizing the DGCR8 mRNA. Conversely, DGCR8 stabilizes Drosha protein via direct protein-protein interaction. This cross-regulation constitutes a homeostatic feedback loop controlling Microprocessor levels. In vitro cleavage reconstitution, knockdown of Drosha leading to increased DGCR8 mRNA/protein, microarray analysis, protein-protein interaction assays Cell High 19135890
2009 The Microprocessor negatively regulates DGCR8 expression by cleaving a hairpin in the 5'UTR of DGCR8 mRNA. Knockdown of Drosha increases DGCR8 mRNA and protein levels. The DGCR8 5'UTR hairpin confers Microprocessor-dependent repression on a luciferase reporter. In vitro reconstitution, Drosha knockdown, luciferase reporter assay, Northern/Western blotting RNA High 19383765
2010 DGCR8 binds pri-miRNAs through highly cooperative binding mediated by the formation of higher-order structures (most likely a trimer of DGCR8 dimers). The amphipathic C-terminal helix is required both for trimerization on pri-miRNAs and for Drosha-mediated cleavage. High cooperativity enables DGCR8 to distinguish pri-miRNAs from non-specific competitors. Biochemical binding assays (EMSAs, gel filtration), in vitro processing assays, electron tomography of DGCR8-pri-miRNA complexes, mutagenesis of C-terminal helix RNA High 20558544
2011 DGCR8 is a ferric [Fe(III)] heme-binding protein that uses two endogenous cysteine side chains (including C352) as axial ligands to form a highly stable heme complex (half-life >4 days). Native DGCR8 binds heme when expressed in eukaryotic cells. This represents the first example of a heme protein with two endogenous cysteine axial ligands. Electronic absorption spectroscopy, magnetic circular dichroism, electron paramagnetic resonance, mutagenesis (P351A, cysteine mutants), selenomethionine substitution, mercury titration, eukaryotic cell expression The Journal of biological chemistry High 21454614
2012 Reduction of the DGCR8 heme iron from ferric [Fe(III)] to ferrous [Fe(II)] state abolishes pri-miRNA processing activity and dramatically increases the rate of heme dissociation. Ferric, but not ferrous, heme restores processing activity to apoDGCR8. ApoDGCR8 dimers show low processing activity in vitro, establishing ferric heme as an activator of miRNA maturation. In vitro pri-miRNA processing assays, electronic absorption/MCD/resonance Raman spectroscopy, heme redox manipulation Proceedings of the National Academy of Sciences of the United States of America High 22308374
2012 DGCR8 HITS-CLIP in human cells revealed that DGCR8 binds hundreds of mRNAs, snoRNAs, and long non-coding RNAs in addition to pri-miRNAs. DGCR8-mediated cleavage of snoRNAs occurs independently of Drosha, implying DGCR8 participates in alternative complexes with other endonucleases. DGCR8 binding to cassette exons regulates alternative splicing isoform abundance. DGCR8 controls stability of MALAT1 lncRNA. HITS-CLIP (high-throughput sequencing with cross-linking immunoprecipitation), knockdown experiments, RNA abundance measurements Nature structural & molecular biology High 22796965
2012 Histone deacetylase 1 (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's affinity for primary miRNA transcripts. Co-immunoprecipitation demonstrating HDAC1 in Drosha/DGCR8 complex, in vitro deacetylation assays, RNA binding affinity measurements, miRNA expression profiling EMBO reports Medium 22222205
2013 Expanded CGG RNA repeats (associated with FXTAS) directly bind DGCR8, resulting in partial sequestration of DGCR8 and its partner DROSHA within nuclear RNA aggregates. This sequestration reduces miRNA processing and decreases mature miRNA levels. Overexpression of DGCR8 rescues neuronal cell death induced by expanded CGG repeats. RNA-protein binding assays, co-localization imaging, miRNA profiling in cells and patient brain tissue, DGCR8 overexpression rescue experiment Cell reports Medium 23478018
2013 ERK/MAPK can phosphorylate DGCR8 at 23 mapped sites. Expression of phosphomimetic DGCR8 increases cellular levels of DGCR8 and Drosha proteins by increasing DGCR8 protein stability (not via altered mRNA levels, localization, or self-association). Phosphomimetic DGCR8-containing Microprocessor complexes exhibit a pro-growth miRNA profile and increased cell proliferation. Phosphoproteomics mapping, phosphomimetic/phosphomutant DGCR8 expression, protein stability assays, kinase inhibitor experiments, miRNA profiling, cell proliferation/scratch closure assays Cell reports Medium 24239349
2014 MeCP2 directly binds to DGCR8 and interferes with the assembly of the Drosha-DGCR8 complex, thereby suppressing nuclear miRNA processing. Gain-of-function MeCP2 inhibits dendritic and spine growth in a manner dependent on its interaction with DGCR8. Co-immunoprecipitation of MeCP2-DGCR8 interaction, Drosha-DGCR8 complex assembly assays, miRNA processing assays, dendritic morphology measurements in neurons with MeCP2/DGCR8 interaction mutants Developmental cell Medium 24636259
2014 In addition to its dsRBDs, DGCR8 uses a dimeric heme-binding domain (RNA-binding heme domain, Rhed) to directly contact pri-miRNAs. The Rhed directs two DGCR8 dimers to bind each pri-miRNA hairpin, with two Rhed-binding sites at both ends of the hairpin. The heme cofactor is required for formation of processing-competent DGCR8-pri-miRNA complexes. RNA binding assays with Rhed deletion/mutant constructs, pri-miRNA processing assays, biochemical analyses of DGCR8 oligomeric state on pri-miRNA Cell reports Medium 24910438
2015 DGCR8 acts as an adaptor for the nuclear exosome complex, preferentially associating with the hRRP6-containing nucleolar form. DGCR8 is essential for recruitment of the exosome to snoRNAs and to human telomerase RNA (hTR/TERC), controlling their stability independently of Drosha. Co-purification of DGCR8 with exosome subunits, co-immunoprecipitation, DGCR8 knockdown with snoRNA/hTR stability measurements, exosome recruitment assays Molecular cell High 26687677
2015 DGCR8 is SUMOylated at the major site K707 by SUMO1, a modification promoted by ERK-activated phosphorylation. SUMOylation enhances DGCR8 protein stability by preventing ubiquitin-proteasome degradation. SUMOylation does not alter DGCR8's association with Drosha or Microprocessor activity, but alters DGCR8's affinity for pri-miRNAs, affecting direct functions of pri-miRNAs in gene silencing. SUMO site mutagenesis (K707R), SUMOylation assays, ubiquitin-proteasome inhibitor experiments, co-immunoprecipitation for Drosha interaction, pri-miRNA binding assays, cell migration assays Nucleic acids research Medium 26202964
2015 The kinase ABL phosphorylates DGCR8 at Tyr267. ABL-dependent Y267 phosphorylation is required for induction of a subset of miRNAs (e.g., miR-34c but not miR-34a) after DNA damage by stimulating Drosha recruitment to selective pri-miRNAs. Y267F-DGCR8 mutant reduces Drosha recruitment to pri-miR-34c and prevents ABL-stimulated processing. In vitro kinase assay, phosphomutant DGCR8 (Y267F) expression, RNA cross-linking assays, Drosha recruitment assays, ABL nuclear import-defective mouse model Science signaling Medium 26126715
2017 Heme bound to DGCR8 is critical for Microprocessor to process pri-miRNAs with high fidelity. Heme-dependent pri-miRNAs fail to properly recruit Drosha, but heme-bound DGCR8 corrects erroneous binding events. Heme induces a conformational change in DGCR8 (rather than changing oligomerization state) and activates DGCR8 to recognize pri-miRNAs by specifically binding near the terminal loop at the 3' single-stranded segment. In vitro processing fidelity assays, Drosha recruitment assays, biophysical characterization of DGCR8 conformation with/without heme, pri-miRNA binding experiments Nature communications Medium 29170488
2017 UV irradiation induces phosphorylation of DGCR8 at serine 153 (S153) by JNK kinases. S153 phosphorylation is critical for resistance to UV, removal of UV-induced DNA lesions, and recovery of RNA synthesis after UV, but is not required for miRNA expression. DGCR8 physically interacts with CSB and RNA Polymerase II. DGCR8 depletion is epistatic to XPA, CSA, and CSB for UV sensitivity, placing DGCR8 in the transcription-coupled nucleotide excision repair pathway independently of miRNA processing. Phosphorylation mapping (S153), phosphomutant DGCR8 expression, DNA lesion removal assays, RNA synthesis recovery assays, co-immunoprecipitation with CSB/RNAPII, genetic epistasis (double knockdown with NER factors), miRNA expression measurement Cell reports High 28380355
2017 DGCR8 maintains heterochromatin organization by interacting with the nuclear envelope protein Lamin B1 and heterochromatin-associated proteins KAP1 and HP1γ. This function is independent of its miRNA processing activity; an N-terminal-truncated DGCR8 (DR8dex2) accelerates senescence in human mesenchymal stem cells without affecting miRNA processing. Overexpression of DGCR8, Lamin B1, KAP1, or HP1γ reverses premature senescent phenotypes. Co-immunoprecipitation of DGCR8 with Lamin B1/KAP1/HP1γ, N-terminal truncation mutant expression, heterochromatin organization analysis, senescence assays, overexpression rescue experiments in hMSCs Nature communications Medium 31350386
2017 DGCR8 directly interacts with the Tcf7l1 mRNA (a core pluripotency network component) through RNA immunoprecipitation. DGCR8 facilitates splicing of Tcf7l1, and this splicing event is required for differentiation of mouse embryonic stem cells. A phosphomutant DGCR8 that restores miRNA levels fails to rescue the exit-from-pluripotency defect, demonstrating a miRNA-independent noncanonical function of DGCR8 in alternative splicing. RNA immunoprecipitation, phosphomutant DGCR8 complementation in Dgcr8-null mESCs, splicing analysis of Tcf7l1, differentiation assays The Journal of cell biology Medium 28100686
2019 DGCR8 interacts with heterochromatin proteins (Lamin B1, KAP1, HP1γ) independently of its miRNA processing role. DGCR8 overexpression alleviated human mesenchymal stem cell aging and mouse osteoarthritis, demonstrating a therapeutic relevance of this non-canonical heterochromatin-stabilizing function. Co-immunoprecipitation, hMSC aging models, mouse osteoarthritis model with DGCR8 overexpression, heterochromatin organization assays Nature communications Medium 31350386
2020 Cryo-EM structure of human Microprocessor (Drosha-DGCR8) with a pri-miRNA docked in the active site revealed: the basal junction is recognized by a four-way intramolecular junction in Drosha triggered by Belt and Wedge regions clamping over ssRNA; two dsRBDs of DGCR8 form a molecular ruler measuring stem length between the two dsRNA-ssRNA junctions; the specific organization of dsRBDs near the apical junction is independent of Drosha core domains. Cryo-electron microscopy structure determination, functional validation of Belt and Wedge regions Molecular cell High 32220646
2020 The Rhed (RNA-binding heme domain, amino acids 285–478) of DGCR8 interacts with the apical UGU motif of pri-miRNAs. Three amino acids at positions 461–463 within Rhed are critical for UGU interaction and essential for accurate and efficient processing of UGU-containing pri-miRNAs in vitro and UGU-miRNA expression in human cells. Within the DGCR8 dimer, amino acids 461–463 from one monomer discriminate between UGU- and non-UGU-pri-miRNAs. Rhed domain mapping with mutagenesis (461–463 mutations), in vitro pri-miRNA processing assays, cellular miRNA expression analysis Communications biology Medium 32620823
2020 ERH (Enhancer of Rudimentary Homolog) is a new component of the Microprocessor complex. Crystal structure reveals ERH uses its hydrophobic groove to bind a conserved region in the N-terminus 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' by enabling Microprocessor loading onto poor substrates aided by high-affinity neighbors. Crystal structure of ERH-DGCR8 N-terminus complex, biochemical binding assays, knockdown of ERH, deletion of DGCR8 N-terminus, pri-miRNA processing assays for clustered vs. individual pri-miRNAs Nucleic acids research High 33035348
2021 Upon X-ray radiation, ATM kinase phosphorylates DGCR8 at serine 677, which facilitates USP51 deubiquitinase to bind, deubiquitinate, and stabilize DGCR8. Stabilized DGCR8 recruits RNF168 to MDC1 and RNF8 at DNA double-strand breaks, promoting H2A ubiquitination and DSB repair. This DSB repair function is independent of DGCR8's Drosha-binding ability. Co-immunoprecipitation of DGCR8 with RNF168/MDC1/RNF8, phosphomutant (S677) and Drosha-binding-deficient DGCR8 constructs, ubiquitination assays, DSB repair foci analysis, radioresistance assays Nature communications High 34188037
2021 USP36, a nucleolar ubiquitin-specific protease, interacts with the Microprocessor complex and promotes DGCR8 SUMOylation specifically by SUMO2. USP36-mediated SUMO2ylation does not affect DGCR8 levels or Drosha-DGCR8 complex formation, but promotes DGCR8 binding to pri-miRNAs, thereby stimulating pri-miRNA processing. Co-immunoprecipitation of USP36 with Microprocessor, in vivo SUMOylation assays, SUMOylation-defective DGCR8 mutant, pri-miRNA binding assays, miRNA processing assays, USP36 knockdown Cancer research communications Medium 36950067
2021 Coilin (Cajal body marker protein) co-immunoprecipitates with DGCR8 and forms a complex with it. Coilin knockdown alters levels of primary and mature miRNAs and affects DGCR8 and Drosha protein levels. Coilin knockdown impairs ERK-mediated phosphorylation of DGCR8, which has been shown to increase DGCR8 protein stability. Co-immunoprecipitation with coilin and DGCR8 constructs, coilin knockdown, miRNA level measurements, DGCR8 phosphorylation analysis Molecular biology of the cell Low 34319763
2012 DGCR8 dimerization and heme binding are evolutionarily conserved properties present not only in vertebrates but also in at least some invertebrates (starfish Patiria miniata). Crystal structure of the Xenopus laevis DGCR8 dimerization domain is very similar to that of human DGCR8, confirming conservation of the dimerization mechanism underlying heme binding surface formation. Crystal structure of Xenopus DGCR8 dimerization domain, heme binding assay of starfish DGCR8 homologue, spectrophotometric determination of heme extinction coefficients PloS one Medium 22768307
2023 DGCR8 has a novel non-canonical function in mRNA subcellular localization. CCDC137 binds DGCR8, and DGCR8 mediates cytoplasmic distribution/localization of specific mRNAs (FOXM1, JTV1, LASP1, FLOT2) bound by CCDC137, thereby increasing their protein expression and activating AKT signaling in hepatocellular carcinoma. Co-immunoprecipitation of CCDC137-DGCR8, APOBEC1-mediated mRNA profiling (C-BERST), mRNA subcellular fractionation, DGCR8 knockdown Journal of experimental & clinical cancer research Low 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 1654 15574589
2006 Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 1134 16751099
2007 DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nature genetics 794 17259983
2009 Posttranscriptional crossregulation between Drosha and DGCR8. Cell 352 19135890
2015 Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors. Cancer cell 245 25670083
2015 Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors. Cancer cell 228 25670082
2011 Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)--a new autoinflammatory syndrome distinct from PAPA syndrome. Journal of the American Academy of Dermatology 222 21745697
2014 MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex. Developmental cell 208 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 202 23478018
2012 DGCR8 HITS-CLIP reveals novel functions for the Microprocessor. Nature structural & molecular biology 181 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 173 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 135 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.) 116 19383765
2019 Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis. Nature communications 108 31350386
2020 Cryo-EM Structures of Human Drosha and DGCR8 in Complex with Primary MicroRNA. Molecular cell 104 32220646
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
2009 Genome-wide identification of targets of the drosha-pasha/DGCR8 complex. RNA (New York, N.Y.) 96 19223442
2018 Noncanonical functions of microRNA pathway enzymes - Drosha, DGCR8, Dicer and Ago proteins. FEBS letters 94 30025156
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
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 80 22308374
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 76 25244517
2013 Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile. Cell reports 75 24239349
2011 Monoallelic deletion of the microRNA biogenesis gene Dgcr8 produces deficits in the development of excitatory synaptic transmission in the prefrontal cortex. Neural development 74 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 68 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
2014 Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PloS one 66 25084529
2012 Histone deacetylase 1 enhances microRNA processing via deacetylation of DGCR8. EMBO reports 66 22222205
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 54 31805011
2011 DiGeorge critical region 8 (DGCR8) is a double-cysteine-ligated heme protein. The Journal of biological chemistry 54 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 46 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 Dgcr8 and Dicer are essential for sex chromosome integrity during meiosis in males. Journal of cell science 39 25934699
2015 SUMOylation at K707 of DGCR8 controls direct function of primary microRNA. Nucleic acids research 39 26202964
2019 Dgcr8 knockout approaches to understand microRNA functions in vitro and in vivo. Cellular and molecular life sciences : CMLS 37 30694346
2014 Drosha-independent DGCR8/Pasha pathway regulates neuronal morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 35 24474768
2021 METTL3 improves cardiomyocyte proliferation upon myocardial infarction via upregulating miR-17-3p in a DGCR8-dependent manner. Cell death discovery 34 34645805
2020 ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8. Nucleic acids research 34 33035348
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
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
2021 Non-canonical function of DGCR8 in DNA double-strand break repair signaling and tumor radioresistance. Nature communications 30 34188037
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
2012 Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells. Biochemical and biophysical research communications 28 22925886
2014 Expression of DGCR8-dependent microRNAs is indispensable for osteoclastic development and bone-resorbing activity. Journal of cellular biochemistry 27 24420069
2020 Select amino acids in DGCR8 are essential for the UGU-pri-miRNA interaction and processing. Communications biology 26 32620823
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 26 28716689
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
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 Deficiency of DGCR8 increases bone formation through downregulation of miR-22 expression. Bone 19 28739418
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
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 18 37542342
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
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
2024 Prevalence, Molecular Landscape, and Clinical Impact of DICER1 and DGCR8 Mutated Follicular-Patterned Thyroid Nodules. The Journal of clinical endocrinology and metabolism 17 38252873
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
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
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.) 14 37254417
2020 DGCR8/miR-106 Axis Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinomas by Downregulating RUNX3. Frontiers in medicine 13 33385002
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
2015 DGCR8 is essential for tumor progression following PTEN loss in the prostate. EMBO reports 10 26206718

Missed literature

Know a paper Affinage missed for DGCR8? Flag it for the maintainers and the community.

No submissions yet.