Affinage

DKC1

H/ACA ribonucleoprotein complex subunit DKC1 · UniProt O60832

Length
514 aa
Mass
57.7 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DKC1 (dyskerin) is the catalytic pseudouridine synthase of H/ACA ribonucleoprotein complexes, functioning at the intersection of ribosome biogenesis, telomere maintenance, mRNA translational control, and transcriptional coactivation. Its pseudouridine synthase activity, dependent on the conserved aspartate in the catalytic XLD motif, is essential for rRNA pseudouridylation and stability; loss of this modification intrinsically alters ribosome translational fidelity and impairs IRES-dependent translation of tumor suppressors including p27 and p53 (PMID:10523634, PMID:25934701, PMID:20587522, PMID:20501855). DKC1 stabilizes human telomerase RNA (hTR) through direct binding via its PUA domain and N-terminal residues, shielding hTR from PAPD5/EXOSC10- and DCP2-mediated decay; disease-causing mutations that impair this interaction reduce hTR accumulation, telomerase activity, and telomere maintenance, causing X-linked dyskeratosis congenita (PMID:26950371, PMID:30931479, PMID:15240872, PMID:19835419). Beyond its RNA-modifying roles, DKC1 associates with RNA polymerase II to pseudouridylate thousands of mRNAs co-transcriptionally in a guide RNA-independent manner—reducing their translational efficiency—and acts as a transcriptional coactivator of OCT4/SOX2 at pluripotency gene enhancers; its nucleolar localization and protein stability are regulated by SUMOylation at K467 and interaction with GAR1 via a SUMO-interacting motif (PMID:37506213, PMID:25407680, PMID:33526451, PMID:23660516).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Identifying dyskerin's subnuclear address established it as a nucleolar protein associated with rRNA processing machinery, setting the stage for understanding its role in ribosome biogenesis.

    Evidence Coimmunoprecipitation with Nopp140 and immunogold EM localization to the dense fibrillar component of nucleoli, coiled bodies, and nucleoplasm in rat cells

    PMID:7798307

    Open questions at the time
    • Enzymatic activity of dyskerin was unknown
    • No functional consequence of the Nopp140 interaction was demonstrated
  2. 1999 High

    Demonstrating that Cbf5/dyskerin is the pseudouridine synthase of H/ACA snoRNPs—and that a single catalytic aspartate is essential—defined its core enzymatic function and linked it to rRNA modification.

    Evidence Active-site mutagenesis (D95A) in yeast Cbf5 abolishing in vivo rRNA pseudouridylation; NLS mapping in human dyskerin showing KRKR and C-terminal lysine clusters direct nuclear/nucleolar import

    PMID:10523634 PMID:10556300 PMID:10744426

    Open questions at the time
    • No structural basis for substrate recognition
    • Relationship to telomerase function not yet tested
  3. 2004 High

    Mouse knock-in of DC mutations revealed that dyskerin simultaneously governs telomerase RNA stability, telomere length, and rRNA pseudouridylation, establishing it as a bifunctional disease gene.

    Evidence A353V and G402E knock-in mouse ES cells showing reduced TERC, telomerase activity, H/ACA snoRNA levels, and rRNA pseudouridylation defects

    PMID:15240872

    Open questions at the time
    • Whether telomere and ribosome defects are separable in disease pathology was unclear
    • Mechanism of TERC destabilization not yet defined
  4. 2006 High

    Crystal structures of the archaeal Cbf5–Nop10–Gar1 complex provided the first atomic-level understanding of dyskerin's catalytic architecture, showing how Nop10 buttresses the active site and how DC mutations cluster on the PUA domain.

    Evidence X-ray crystallography at 1.95–2.1 Å resolution with mutagenesis validation and cross-species assembly assays

    PMID:16286935 PMID:16427014

    Open questions at the time
    • No full human dyskerin structure
    • Mechanism of guide RNA-directed substrate positioning not resolved at atomic level
  5. 2009 High

    A series of studies established that dyskerin mutations damage telomeres through mechanisms beyond simple shortening, activate the ATM/p53 DNA damage response, and that dyskerin controls telomerase by stabilizing TERC—with TERC overexpression fully rescuing the telomerase defect.

    Evidence Mouse genetic models with X-inactivation skewing and γH2AX-telomere colocalization; siRNA knockdown with retroviral TERC rescue in human cells; single-molecule TCCD showing DC mutations impair direct dyskerin–hTR binding

    PMID:18626023 PMID:18936525 PMID:19835419 PMID:20008900

    Open questions at the time
    • Specific RNA decay pathways degrading hTR in dyskerin deficiency were not yet identified
    • Whether A353V tetramer assembly defect is the primary pathogenic mechanism remained uncertain
  6. 2009 High

    Conditional hepatocyte knockout demonstrated that dyskerin is essential for rRNA processing and cell division—but not cell survival—and identified c-MYC and later GATA1 as direct transcriptional regulators of DKC1.

    Evidence Cre/loxP Dkc1 deletion in mouse liver with rRNA precursor accumulation and p53 checkpoint activation; ChIP showing c-MYC binding DKC1 promoter/intron 1; ChIP showing GATA1 binding in erythroid cells

    PMID:17822678 PMID:19917719 PMID:31413099

    Open questions at the time
    • Transcriptional regulation in non-hematopoietic/non-hepatic tissues unexplored
    • Relative contribution of ribosome vs. telomerase defects to p53 activation unclear
  7. 2010 High

    Dyskerin's ribosome biogenesis function was linked to translational control of tumor suppressors: impaired rRNA pseudouridylation selectively reduces IRES-dependent translation of p27 and p53, connecting dyskerin to cancer biology independently of telomerase.

    Evidence In vivo bioluminescent IRES reporters and 48S preinitiation complex assembly assays in DKC1 hypomorphic mice; siRNA knockdown with IRES reporters in breast cancer and primary cells

    PMID:20501855 PMID:20587522

    Open questions at the time
    • Full catalog of IRES elements affected by dyskerin not defined
    • Whether IRES translation defects contribute to DC pathology unknown
  8. 2011 High

    The Shq1–Cbf5 crystal structure revealed that the assembly chaperone SHQ1 protects dyskerin from non-specific RNA binding before H/ACA RNA loading, and that DC mutations in the C-terminal extension interfere with this chaperoning step.

    Evidence X-ray crystallography of Shq1–Cbf5–Nop10–Gar1 complex with mutagenesis and yeast growth assays

    PMID:22117216

    Open questions at the time
    • Timing of SHQ1 release and H/ACA RNA loading in vivo not resolved
    • Relevance to human telomerase assembly not directly tested
  9. 2013 High

    Cell-free translation with purified ribosomes proved that rRNA pseudouridylation deficiency alone—without changes in ribosomal protein composition—intrinsically alters ribosome translational fidelity and IRES-dependent translation, while catalytically dead dyskerin (D125A) produces unstable rRNAs lacking pseudouridine.

    Evidence Ribosome purification from dyskerin-depleted cells with cell-free translation and mass spectrometry; D125A knock-in mouse fibroblasts with rRNA stability assays

    PMID:23726835 PMID:25934701

    Open questions at the time
    • Structural basis for how pseudouridine loss alters ribosome decoding unknown
    • Which specific rRNA pseudouridylation sites are most functionally critical not determined
  10. 2013 Medium

    SUMOylation was identified as a post-translational modification of dyskerin that regulates its stability and telomerase function, with DC-causing mutations mapping to SUMO consensus sites impairing hTR accumulation.

    Evidence In vivo SUMOylation assays, mutation of consensus sites, telomerase and telomere length assays

    PMID:23660516

    Open questions at the time
    • Specific SUMO E3 ligase responsible not identified in this study
    • Whether SUMOylation affects rRNA pseudouridylation independently of protein stability untested
  11. 2014 High

    An unexpected transcriptional coactivator role was uncovered: purified DKC1 complex mediates OCT4/SOX2-dependent transcription in a reconstituted in vitro system, occupies pluripotency gene enhancers, and is required for efficient iPSC generation.

    Evidence Biochemically defined in vitro transcription of Nanog, ChIP-seq in ESCs, DKC1 depletion reducing reprogramming efficiency

    PMID:25407680

    Open questions at the time
    • Mechanism by which an H/ACA RNP complex coactivates Pol II transcription is unknown
    • Whether this role requires pseudouridine synthase catalytic activity untested
  12. 2016 High

    The RNA decay pathways responsible for hTR destruction in dyskerin deficiency were mapped: PAPD5-mediated oligoadenylation feeds hTR to EXOSC10 for 3′→5′ decay, while DCP2 decapping enables 5′→3′ decay; blocking these pathways rescues telomerase in dyskerin-deficient cells.

    Evidence Knockdown of PAPD5, EXOSC10, DCP2, and XRN1 with epistasis experiments; hTR oligoadenylation and localization assays

    PMID:26950371

    Open questions at the time
    • Whether pharmacological inhibition of PAPD5 can treat DC was not demonstrated in this study
    • Relative contribution of 3′ vs. 5′ decay in patient cells not quantified
  13. 2019 High

    Mapping of dyskerin–hTR contact sites showed that N-terminal residues K39/K43 and PUA domain residue A353 are independently required for binding both mature and polyadenylated hTR precursors, placing dyskerin engagement upstream of hTR maturation.

    Evidence Co-IP with multiple dyskerin variants, hTR accumulation and polyadenylation assays, rescue in dyskerin-deficient cells

    PMID:30931479

    Open questions at the time
    • Whether the N-terminal and PUA contacts are simultaneous or sequential in the assembly pathway is unresolved
  14. 2021 High

    SUMOylation at K467 within the NLS was shown to drive dyskerin's nucleolar localization, and GAR1 was found to recognize SUMOylated dyskerin through a SUMO-interacting motif, coupling post-translational modification to subnuclear targeting and hTR association.

    Evidence SUMO3 fusion constructs directing cytoplasmic dyskerin to the nucleus; GAR1 SIM analysis; dyskerin–hTR interaction assays with mislocalized variants

    PMID:33526451

    Open questions at the time
    • Whether SENP3-mediated deSUMOylation at K467 specifically controls nucleolar exit not tested in this study
    • In vivo stoichiometry of SUMOylated vs. unmodified dyskerin unknown
  15. 2023 High

    Dyskerin was revealed to associate with RNA Pol II and pseudouridylate thousands of mRNAs co-transcriptionally in a guide RNA-independent manner, with mRNA pseudouridylation suppressing translation—establishing a direct regulatory role for dyskerin in the mRNA translatome beyond its known rRNA and snRNA targets.

    Evidence RIP-seq, transcriptome-wide pseudouridylation profiling, ribosome profiling, de novo protein synthesis measurement, DC patient cell validation

    PMID:37506213

    Open questions at the time
    • Sequence or structural determinants for guide-independent mRNA substrate selection unknown
    • Whether mRNA pseudouridylation defects contribute to DC pathology or are incidental is not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how dyskerin selects mRNA substrates without guide RNAs; the structural basis for its transcriptional coactivator function; and the relative pathogenic contributions of ribosome, telomere, and mRNA pseudouridylation defects in dyskeratosis congenita.
  • No structure of human dyskerin in complex with RNA Pol II or mRNA substrates
  • Relative disease contribution of ribosome vs. telomere vs. mRNA pseudouridylation defects not disentangled
  • Mechanism of transcriptional coactivation at OCT4/SOX2 enhancers completely unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 7 GO:0003723 RNA binding 5 GO:0140110 transcription regulator activity 2
Localization
GO:0005730 nucleolus 4 GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 8 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1266738 Developmental Biology 1
Partners
GAR1NAF1NHP2NOP10NOPP140SENP3SHQ1SMUG1
Complex memberships
H/ACA snoRNPNAF1-dyskerin-NOP10-NHP2 pre-RNPtelomerase holoenzyme

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 NAP57 (rat ortholog of DKC1/dyskerin) is associated with nucleolar protein Nopp140 in a stoichiometric complex, as shown by coimmunoprecipitation, and colocalizes with Nopp140 to the dense fibrillar component of the nucleolus, coiled bodies, and nucleoplasm. Coimmunoprecipitation, immunofluorescence, immunogold electron microscopy The Journal of cell biology High 7798307
1999 Yeast Cbf5p (ortholog of DKC1) is the pseudouridine synthase component of box H/ACA snoRNPs; substitution of the conserved aspartic acid in the XLD motif (D95A) abolishes in vivo pseudouridylation of rRNA, and other active-site mutations reduce pseudouridylation and impair association with H/ACA snoRNAs. In vitro mutagenesis, in vivo pseudouridylation assays, growth phenotype analysis, RNA co-precipitation Molecular and cellular biology High 10523634
1999 Dyskerin localizes to the nucleolus via multiple nuclear localization signals (NLS); the KRKR sequence mediates nuclear import and C-terminal lysine-rich clusters influence the rate of nucleolar accumulation; DKC1 disease mutations do not cause mislocalization. EGFP fusion protein live imaging, time-course expression analysis, deletion/mutation analysis of NLS constructs in mammalian cell lines Human molecular genetics High 10556300
1999 Dyskerin contains a C-terminal nuclear localization signal (amino acids 467–475, KKEKKKSKK) that is necessary and sufficient for nuclear entry; dyskerin does not interact with FANCA. Epitope-tagged expression in HeLa/COS-1 cells, deletion mapping, coimmunoprecipitation Blood cells, molecules & diseases Medium 10744426
2004 Mouse dyskerin mutations A353V and G402E lead to reduced accumulation of telomerase RNA (TERC), decreased telomerase activity, and reduced H/ACA snoRNA levels; A353V but not G402E causes continuous telomere shortening; both mutations cause defective rRNA pseudouridylation and impair pre-rRNA processing. Mouse embryonic stem cell knock-in model, telomerase activity assay (TRAP), telomere length measurement, Northern blotting, pseudouridylation assays Proceedings of the National Academy of Sciences of the United States of America High 15240872
2006 Crystal structure of archaeal Cbf5 (DKC1 ortholog)–Nop10–Gar1 complex at 2.1 Å reveals that Cbf5 has unique structural properties among pseudouridine synthases consistent with RNA-guided catalysis; Nop10 buttresses the Cbf5 active site; the complex contains bidirectional basic troughs extending the active-site cleft; a dyskeratosis congenita mutation cluster maps to the modeled dyskerin PUA domain. X-ray crystallography at 2.1 Å, structural modeling of full RNP with substrate RNA Molecular cell High 16427014
2005 Archaeal Cbf5 and Nop10 co-crystal structure at 1.95 Å shows Nop10 buttresses the Cbf5 active site and reveals two basic troughs forming a tripartite RNA-binding surface; Cbf5 can assemble with yeast Nop10 and human telomerase RNA, indicating phylogenetic conservation of the Cbf5-Nop10 architecture. X-ray crystallography, mutagenesis of RNA-binding surface, cross-species assembly assays Nature structural & molecular biology High 16286935
2006 Dyskerin gene silencing in MCF-7 breast cancer cells reduces both telomerase activity (through reduction of TERC levels) and rRNA pseudouridylation, demonstrating that dyskerin expression directly governs both functions. siRNA knockdown, telomerase activity assay, pseudouridylation measurement The Journal of pathology High 16841302
2009 Mouse dyskerin mutations cause a growth disadvantage and enhanced DNA damage response (via ATM/p53 pathway) independently of telomere shortening; the growth disadvantage is telomerase-dependent; DNA damage foci colocalize with telomeres, indicating dyskerin affects telomere maintenance independent of length. Mouse genetic model, X-inactivation skewing assay, γH2AX/ATM/p53 pathway analysis, etoposide treatment, colocalization of damage foci with telomeres Proceedings of the National Academy of Sciences of the United States of America High 18626023
2009 Conditional deletion of Dkc1 in mouse hepatocytes inhibits rRNA processing (accumulation of large precursors), prevents fibrillarin accumulation in nucleoli, induces p53-dependent cell cycle checkpoint, and blocks proliferation; hepatocytes can survive without dyskerin but cannot divide. Cre/loxP conditional knockout, rRNA processing analysis, immunohistochemistry for fibrillarin, p53 pathway analysis, carbon tetrachloride-induced liver regeneration assay Molecular and cellular biology High 19917719
2009 Dyskerin (DKC1) mutations associated with X-linked dyskeratosis congenita significantly impair the direct dyskerin–hTR interaction as shown by single-molecule two-color coincidence detection; the H/ACA domain of hTR is required for dyskerin binding; hTR mutations associated with autosomal dominant DC did not affect this interaction. Single-molecule two-color coincidence detection (TCCD), systematic hTR deletion analysis, DC-associated mutation analysis Biochemistry High 19835419
2009 DKC1 is a direct transcriptional target of c-MYC; c-MYC binds two conserved regions in the DKC1 promoter and intron 1 as shown by chromatin immunoprecipitation; DKC1 induction by c-MYC is independent of de novo protein synthesis. Chromatin immunoprecipitation (ChIP), conditional c-MYC activation system, cycloheximide chase Biochemical and biophysical research communications Medium 17822678
2009 Dyskerin knockdown reduces telomerase activity through reduction of TERC levels independently of TERT expression; retroviral overexpression of TERC abolishes the telomerase impairment caused by dyskerin knockdown, placing dyskerin upstream of TERC stability in the telomerase pathway. siRNA knockdown, telomerase activity assay, TERC/TERT quantification, retroviral TERC overexpression rescue Cellular oncology High 18936525
2009 The most prevalent DC mutation A353V in dyskerin does not prevent formation of the NAF1-dyskerin-NOP10-NHP2 tetramer required for H/ACA pre-RNP assembly but slightly reduces assembly with the H/ACA-like domain of hTR, revealing mutation-specific effects on RNP biogenesis. In vivo H/ACA pre-RNP assembly assay, protein co-immunoprecipitation, hTR H/ACA domain interaction assay Human molecular genetics High 20008900
2010 Impaired dyskerin function reduces IRES-mediated translation of p27 mRNA; DKC1 has a critical role in assembling the 48S translational preinitiation complex at the p27 IRES element; reduced DKC1 activity (including the somatic S485G cancer mutation) decreases p27 protein levels and increases pituitary tumorigenesis in mice. Mouse DKC1 hypomorphic model, bioluminescent IRES translation reporter in vivo, 48S complex assembly assay, DKC1 mutation analysis in human tumors Cancer research High 20587522
2010 Dyskerin knockdown causes a selective defect in p53 mRNA IRES-mediated translation, reducing p53 protein levels and transcriptional activity, in breast cancer cells and primary mammary epithelial progenitor cells; this effect is independent of telomerase function. siRNA knockdown, IRES-reporter assay, p53 protein/activity measurement, rescue experiments Cancer research High 20501855
2011 Crystal structure of the Shq1-Cbf5-Nop10-Gar1 complex shows that the Shq1-specific domain contacts the PUA domain and disordered C-terminal extension (CTE) of Cbf5; Shq1 shares an overlapping binding surface with H/ACA RNA; DC mutations in the CTE likely interfere with Shq1 binding; Shq1 functions as an assembly chaperone protecting Cbf5 from non-specific RNA binding before H/ACA RNA assembly. X-ray crystallography, mutagenesis, yeast growth assays, binding assays The EMBO journal High 22117216
2012 SMUG1 (base excision repair enzyme) directly interacts with DKC1, colocalizes with DKC1 in nucleoli and Cajal bodies, associates with the 47S rRNA precursor processed by DKC1, and contributes to rRNA quality control; combined SMUG1 and DKC1 depletion causes accumulation of 5-hydroxymethyluridine in rRNA. Co-immunoprecipitation, immunofluorescence colocalization, siRNA depletion, rRNA quality analysis, 5-hmU measurement Molecular cell High 23246433
2013 Dyskerin can be modified by SUMOylation; DC-causing mutations in dyskerin SUMOylation consensus sites impair hTR accumulation, telomerase activity, and telomere maintenance; SUMOylation is required for dyskerin stability. SUMOylation assay, mutation of SUMOylation consensus sites, telomerase activity assay, telomere length measurement, dyskerin stability assay Human molecular genetics Medium 23660516
2013 Dyskerin depletion increases VEGF mRNA IRES-mediated translation, leading to increased VEGF production without upregulating VEGF mRNA; dyskerin differentially affects translation from different viral and cellular IRES elements. siRNA knockdown, IRES-reporter assay, VEGF protein/mRNA quantification in transformed and primary cells Nucleic acids research Medium 23821664
2013 Ribosomes purified from dyskerin-depleted human cells show reduced rRNA pseudouridylation, altered translational fidelity, and impaired IRES-mediated translation in a cell-free system; ribosomal protein composition is unchanged, demonstrating that rRNA pseudouridylation deficiency is sufficient to intrinsically alter ribosome function. Ribosome purification, cell-free translation assay, mass spectrometry for ribosomal protein composition, pseudouridylation quantification FASEB journal High 25934701
2013 Catalytically inactive dyskerin (D125A mutation) is extremely unstable; cells expressing only D125A produce mature cytoplasmic rRNAs lacking pseudouridine, but these are very unstable; pseudouridine is required to stabilize rRNA secondary structure essential for function. Mouse embryonic fibroblast knock-in of catalytically inactive DKC1 D125A, rRNA stability assay, pseudouridylation analysis FEBS letters High 23726835
2014 The DKC1 ribonucleoprotein complex functions as an OCT4/SOX2 coactivator in embryonic stem cells; purified DKC1 complex mediates OCT4/SOX2-dependent transcription of the Nanog gene in a biochemically defined in vitro transcription system; DKC1 occupies enhancers and regulates pluripotency gene expression; DKC1 depletion significantly decreases iPSC generation efficiency. Biochemically defined in vitro transcription system, affinity purification, ChIP-seq, DKC1 depletion in fibroblast reprogramming eLife High 25407680
2016 Defects in dyskerin binding to hTR lead to hTR degradation through PAPD5-mediated oligoadenylation followed by 3'-to-5' degradation by EXOSC10, and through decapping and 5'-to-3' decay by DCP2/XRN1; PARN deadenylates hTR to limit EXOSC10-mediated degradation; knockdown of DCP2 and/or EXOSC10 rescues telomerase activity and hTR localization in dyskerin-deficient cells. Knockdown of decay pathway components, hTR oligoadenylation assay, telomerase activity assay, hTR localization analysis, epistasis experiments Nature structural & molecular biology High 26950371
2016 SMN and coilin negatively regulate dyskerin association with telomerase RNA; reduction of SMN or coilin increases dyskerin-hTR association; clinically defined SMN mutants show altered association with telomerase complex proteins. RIP (RNA immunoprecipitation), SMN/coilin knockdown, co-immunoprecipitation, SMN patient mutant analysis Biology open Medium 27215323
2017 SHQ1 mutations that map to the SHQ1-NAP57(dyskerin) interface impair the interaction of recombinant SHQ1 variants with NAP57 in pulldown assays, and cause a severe neurological disorder resembling Hoyeraal-Hreidarsson syndrome. Pulldown assay with recombinant proteins, exome sequencing, structural mapping of mutation sites Molecular genetics & genomic medicine Medium 29178645
2019 N-terminal residues of dyskerin (K39, K43) and PUA domain residue A353 are required for interaction with hTR and polyadenylated hTR species; loss of these interactions impairs hTR accumulation and telomerase activity; hTR precursor degradation occurs upstream of mature complex assembly when dyskerin binding is absent. X-DC mutant analysis, Co-IP with dyskerin variants, hTR accumulation and polyadenylation assay, rescue experiments in dyskerin-deficient cells Nucleic acids research High 30931479
2020 DKC1 p.Glu206Lys and NOP10 p.Thr16Met mutations fall at the dyskerin-NOP10 binding interface, impair the dyskerin-NOP10 interaction, disrupt the catalytic pseudouridylation site, and cause reduced rRNA pseudouridylation; zebrafish dkc1 mutants show reduced 18S pseudouridylation, ribosomal dysregulation, and cell-cycle defects in the absence of telomere attrition. Patient mutation analysis, structural mapping, pseudouridylation assay of patient rRNA, zebrafish dkc1 mutant model, cell-cycle analysis Proceedings of the National Academy of Sciences of the United States of America High 32554502
2021 SUMOylation of dyskerin at the K467 site in the C-terminal N/NoLS is required for nucleolar localization; mimicking constitutive SUMOylation drives nuclear accumulation of a cytoplasmic dyskerin variant; GAR1 contains a SUMO-interacting motif that mediates its interaction with dyskerin; mislocalization of dyskerin (cytoplasm or outside nucleolus) reduces dyskerin-hTR interaction. SUMO3 fusion constructs, nuclear/subnuclear localization assays, GAR1 SUMO-interacting motif analysis, dyskerin-hTR interaction assay Molecular and cellular biology High 33526451
2021 DKC1 binds to and stabilizes mRNAs of ribosomal proteins (RPL10A, RPL22L1, RPL34, RPS3), as shown by RIP-seq and RNA decay analyses; the catalytically inactive D125A mutant of DKC1 does not accelerate cell growth, demonstrating that catalytic activity is required for its oncogenic function; DKC1-regulated RPs interact with HRAS and suppress the RAS/RAF/MEK/ERK pathway. Proteomics, RNA immunoprecipitation sequencing (RIP-seq), RNA decay assay, catalytically inactive mutant D125A, RAS pathway analysis Advanced science High 34026451
2023 Dyskerin associates with RNA polymerase II, binds thousands of mRNAs, and pseudouridylates them in a guide RNA-independent manner at chromatin; mRNAs with fewer pseudouridines in dyskerin-depleted cells are translated more efficiently, indicating that mRNA pseudouridylation by dyskerin inhibits translation; mRNA pseudouridylation is severely reduced in dyskeratosis congenita patient cells. RIP-seq, pseudouridylation profiling, ribosome profiling/de novo protein synthesis measurement, DC patient cell analysis, DKC1 knockdown Science advances High 37506213
2023 SENP3 interacts with DKC1 and catalyzes deSUMOylation of DKC1 at three lysine residues (SUMO3 modification); SENP3-mediated deSUMOylation causes DKC1 instability and disruption of snoRNP protein interactions, impairing PDAC cell migration. Co-immunoprecipitation, in vivo SUMOylation assay, SUMO3 site mapping by mutagenesis, PDAC migration assay, xenograft model Cell death and differentiation Medium 37188742
2019 GATA1 directly regulates DKC1 transcription in erythroid cells; DKC1 upregulation during erythroid commitment drives increased telomerase activity; DKC1 overexpression is sufficient to extend telomeres in erythroleukemia cells; DKC1 upregulation is necessary for erythroblast expansion. Chromatin immunoprecipitation (ChIP), reporter assay, DKC1 knockdown/overexpression in erythroid differentiation, telomere length measurement, telomerase activity assay Haematologica Medium 31413099
2019 DKC1 facilitates HIF-1α expression by directly regulating HIF-1α promoter activity, as demonstrated by chromatin immunoprecipitation, and promotes VEGF expression and tumor angiogenesis in colorectal cancer. Chromatin immunoprecipitation (ChIP), HIF-1α/VEGF expression analysis, in vitro and in vivo angiogenesis assays British journal of cancer Medium 31857720
2022 Dyskerin binds cytoplasmic H/ACA-box-containing snoRNA-retaining transcripts (snoRTs) as shorter 3' fragments; dyskerin depletion affects expression and polysome association of snoRT-containing mRNA isoforms; dyskerin dysregulation alters nuclear hormone receptor ligand dependence in breast cancer cells. RIP-seq of cytoplasmic dyskerin RNA interactome, polysome profiling, knockdown experiments, xenograft in nude mice Genome biology Medium 35996163

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 NAP57, a mammalian nucleolar protein with a putative homolog in yeast and bacteria. The Journal of cell biology 222 7798307
1999 X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. American journal of human genetics 193 10364516
1999 Point mutations in yeast CBF5 can abolish in vivo pseudouridylation of rRNA. Molecular and cellular biology 191 10523634
1999 Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1. British journal of haematology 174 10583221
2004 Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing. Proceedings of the National Academy of Sciences of the United States of America 151 15240872
2010 Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis. Cancer research 140 20587522
2006 Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided pseudouridylation and dyskeratosis congenita. Molecular cell 134 16427014
2014 A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia. Chest 112 24504062
2016 Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects. Nature structural & molecular biology 98 26950371
2009 DKC1 overexpression associated with prostate cancer progression. British journal of cancer 97 19755982
2006 Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer. The Journal of pathology 96 16841302
2005 The Cbf5-Nop10 complex is a molecular bracket that organizes box H/ACA RNPs. Nature structural & molecular biology 94 16286935
2010 Novel dyskerin-mediated mechanism of p53 inactivation through defective mRNA translation. Cancer research 86 20501855
2013 Telomere phenotypes in females with heterozygous mutations in the dyskeratosis congenita 1 (DKC1) gene. Human mutation 84 23946118
2002 Targeted disruption of Dkc1, the gene mutated in X-linked dyskeratosis congenita, causes embryonic lethality in mice. Oncogene 83 12400016
2021 Dual Inhibition of DKC1 and MEK1/2 Synergistically Restrains the Growth of Colorectal Cancer Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 82 34026451
2008 A pathogenic dyskerin mutation impairs proliferation and activates a DNA damage response independent of telomere length in mice. Proceedings of the National Academy of Sciences of the United States of America 78 18626023
2021 Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance. RNA (New York, N.Y.) 77 34556550
2019 DKC1 enhances angiogenesis by promoting HIF-1α transcription and facilitates metastasis in colorectal cancer. British journal of cancer 73 31857720
2001 Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis. Human genetics 72 11379875
2008 Dyskerin is a component of the Arabidopsis telomerase RNP required for telomere maintenance. Molecular and cellular biology 66 18212040
2000 A CBF5 mutation that disrupts nucleolar localization of early tRNA biosynthesis in yeast also suppresses tRNA gene-mediated transcriptional silencing. Proceedings of the National Academy of Sciences of the United States of America 63 11069303
2012 The human base excision repair enzyme SMUG1 directly interacts with DKC1 and contributes to RNA quality control. Molecular cell 62 23246433
1999 Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita. Human molecular genetics 62 10556300
2002 A novel DKC1 mutation, severe combined immunodeficiency (T+B-NK- SCID) and bone marrow transplantation in an infant with Hoyeraal-Hreidarsson syndrome. British journal of haematology 60 12437656
2015 Human ribosomes from cells with reduced dyskerin levels are intrinsically altered in translation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 58 25934701
2022 Sex differences in telomere length, lifespan, and embryonic dyskerin levels. Aging cell 53 35441417
2019 Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion. Investigational new drugs 50 30847721
2011 Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita. Journal of medical genetics 49 21415081
2013 Dyskerin depletion increases VEGF mRNA internal ribosome entry site-mediated translation. Nucleic acids research 48 23821664
2009 Effects of dyskeratosis congenita mutations in dyskerin, NHP2 and NOP10 on assembly of H/ACA pre-RNPs. Human molecular genetics 48 20008900
2014 Human dyskerin: beyond telomeres. Biological chemistry 47 24468621
2011 Structure of the Shq1-Cbf5-Nop10-Gar1 complex and implications for H/ACA RNP biogenesis and dyskeratosis congenita. The EMBO journal 47 22117216
2005 Elucidating the role of H/ACA-like RNAs in trans-splicing and rRNA processing via RNA interference silencing of the Trypanosoma brucei CBF5 pseudouridine synthase. The Journal of biological chemistry 47 16107339
2008 Relationship between dyskerin expression and telomerase activity in human breast cancer. Cellular oncology : the official journal of the International Society for Cellular Oncology 43 18936525
2009 Dyskerin ablation in mouse liver inhibits rRNA processing and cell division. Molecular and cellular biology 42 19917719
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