Dyskerin is an RNA-binding pseudouridine synthase and a core protein of H/ACA ribonucleoprotein particles. Guide RNAs position RNA substrates for uridine isomerization during ribosomal and spliceosomal RNA maturation, and dyskerin-dependent pseudouridylation also occurs in human mRNAs. In telomerase, dyskerin binds and stabilizes the H/ACA region of telomerase RNA, enabling assembly and maintenance of the active enzyme while TERT carries out DNA synthesis. Dyskerin occupies nucleolar, nucleoplasmic and Cajal-body pools; a shorter natural product has reported cytoplasmic localization. Pathogenic DKC1 variants cause X-linked dyskeratosis congenita, linking altered RNA biology to telomere dysfunction.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000455 enzyme-directed rRNA pseudouridine synthesis | IMP PMID:25219674 Transcriptome-wide mapping reveals widespread dynamic-regula... | MODIFY | Summary: Dyskerin-dependent rRNA pseudouridylation uses the H/ACA guide-RNA mechanism. Reason: GO:0000455 specifically requires site selection without a guide RNA. PMID:25219674 distinguishes H/ACA-guided Cbf5/dyskerin from stand-alone PUS enzymes. Its human HEK293 DKC1 knockdown reduces rRNA pseudouridylation, and patient fibroblasts show smaller reductions; these are cellular modification measurements rather than purified guide-independent catalysis. The established H/ACA mechanism therefore supports GO:0000454. The original IMP source and relationship remain unchanged. Proposed replacements: snoRNA guided rRNA pseudouridine synthesis Supporting Evidence: |
| GO:0000495 box H/ACA sno(s)RNA 3'-end processing | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved H/ACA particle assembly supports snoRNA 3β²-end maturation. Reason: The literal IBD at PTN000565614 lies on the human DKC1 lineage. Its yeast Cbf5 donor is experimentally grounded in PMID:15964797: cotranscriptional Cbf5 recruitment and depletion-dependent snoRNA readthrough support a structural assembly/quality-control role in 3β²-end formation. DKC1 inherits this H/ACA function; this does not assign a cleavage nuclease activity or claim the yeast assay was performed in human cells. Supporting Evidence: GO_REF:0000033 PMID:15964797 cotranscriptional recruitment of Cbf5p and Nhp2p on H/ACA snoRNA precursors |
| GO:0001522 pseudouridine synthesis | IEA GO_REF:0000002 | MODIFY | Summary: The conserved pseudouridine synthase domain supports defined RNA-modification processes. Reason: The actual IPR020103 membership and InterPro2GO mapping support pseudouridine formation. Human rRNA and mRNA evidence and the reconstructed H/ACA snRNA lineage permit RNA-specific refinements instead of an undifferentiated synthesis term; these are different substrates of the same chemistry, not separate enzyme mechanisms. Proposed replacements: snoRNA guided rRNA pseudouridine synthesis snRNA pseudouridine synthesis mRNA pseudouridine synthesis |
| GO:0001650 fibrillar center | IDA GO_REF:0000052 | ACCEPT | Summary: Dyskerin is detected in the nucleolar fibrillar center. Reason: The current Human Protein Atlas record matches DKC1/O60832 and reports supported fibrillar-center and nucleoplasm localization. This is an inspected ICC/IF data record, not an independent interpretation of microscopy pixels or a product-specific assay. Supporting Evidence: GO_REF:0000052 |
| GO:0003720 telomerase activity | IDA PMID:12135483 Differential regulation of telomerase activity by six telome... | MARK AS OVER ANNOTATED | Summary: Dyskerin supports telomerase but is not its reverse-transcriptase catalyst. Reason: GO:0003720 describes RNA-templated DNA polymerization. PMID:12135483 reports dyskerin as a telomerase component and an antisense-dependent change in whole-cell telomerase activity; its full experimental text was unavailable. Independent human holoenzyme structural evidence establishes the H/ACA RNA-stabilizing contribution of dyskerin, whereas TERT performs DNA synthesis. The autonomous molecular-activity assertion therefore exceeds the established subunit role. Preserve the positive experiment and the separately accepted contributes_to assertion; this is not a claim of a wrong protein or absent telomerase contribution. |
| GO:0003720 telomerase activity | IDA PMID:23685356 HOT1 is a mammalian direct telomere repeat-binding protein c... | ACCEPT | Summary: Dyskerin contributes to an active telomerase ribonucleoprotein. Reason: This source explicitly makes the weaker contributes_to assertion. Human HeLa dyskerin immunoprecipitates served as a positive telomerase-activity control, and dyskerin was recovered with HOT1-associated H/ACA components. The result is consistent with a structural/RNA-stabilizing subunit of the active RNP, without assigning TERT-mediated DNA polymerization to dyskerin itself. Supporting Evidence: |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MODIFY | Summary: UV mRNA capture identifies DKC1 as an mRNA-binding protein. Reason: PMID:22658674 Table S1 lists ENSG00000130826/DKC1 in the HeLa mRNA interactome, identified after crosslinking and not in controls. The original protocol uses direct UV RNA-protein crosslinking, oligo(dT) capture and stringent washes. This supports mRNA binding rather than generic RNA binding; it does not identify the poly(A) tail as the contact site or establish a particular natural DKC1 product. Proposed replacements: mRNA binding |
| GO:0003723 RNA binding | IEA GO_REF:0000002 | MODIFY | Summary: RNA-binding domains support the established H/ACA, telomerase and mRNA substrates. Reason: All four cited InterPro memberships and their RNA-binding mappings were recovered. The broad domain prediction is consistent with DKC1 biology, while direct H/ACA-RNP and telomerase-RNA studies plus the human mRNA capture identify more informative RNA classes. The domain matches alone do not identify individual RNA contacts. |
| GO:0003723 RNA binding | IPI PMID:18082603 Purification of human telomerase complexes identifies factor... | MODIFY | Summary: The RNA association is with telomerase RNA. Reason: Human telomerase and dyskerin affinity purifications recover hTR, with knockdown effects on its accumulation. This supports telomerase RNA binding at the RNP level, not an isolated dyskerin affinity measurement. The imported RNAcentral identifier is preserved: its current 541-nt record contains the canonical 451-nt hTR sequence but does not establish the exact historical construct endpoint. Proposed replacements: telomerase RNA binding Supporting Evidence: |
| GO:0003723 RNA binding | IPI PMID:20351177 Specificity and stoichiometry of subunit interactions in the... | MODIFY | Summary: The RNA association is with telomerase RNA. Reason: Controlled tandem-tag purifications in human cells demonstrate two dyskerin-containing H/ACA units assembled on hTR. This supports telomerase RNA binding at the RNP level, not an isolated dyskerin affinity measurement. The imported RNAcentral identifier is preserved: its current 541-nt record contains the canonical 451-nt hTR sequence but does not establish the exact historical construct endpoint. Proposed replacements: telomerase RNA binding Supporting Evidence: |
| GO:0003723 RNA binding | IPI PMID:22527283 An enhanced H/ACA RNP assembly mechanism for human telomeras... | MODIFY | Summary: The RNA association is with telomerase RNA. Reason: Human dyskerin-containing preassembled complexes bind the hTR 3β² H/ACA hairpin; the BIO and ACA elements enhance assembly. This supports telomerase RNA binding at the RNP level, not an isolated dyskerin affinity measurement. The imported RNAcentral identifier is preserved: its current 541-nt record contains the canonical 451-nt hTR sequence but does not establish the exact historical construct endpoint. Proposed replacements: telomerase RNA binding Supporting Evidence: |
| GO:0003723 RNA binding | TAS PMID:10591218 A telomerase component is defective in the human disease dys... | MODIFY | Summary: The reported RNA association has identified H/ACA snoRNA and telomerase-RNA partners. Reason: The PMID:10591218 abstract explicitly reports dyskerin association with H/ACA small nucleolar RNAs and human telomerase RNA. The full 1999 original was not recovered, so its precise immunoprecipitation conditions and directness are not independently claimed. The separately inspected human holoenzyme structure in PMID:29695869 resolves dyskerin contacts with the hTR H/ACA hairpins and corroborates telomerase-RNA binding. These defined RNA classes are more informative than unrestricted RNA binding; this does not assign reverse-transcriptase activity to dyskerin. Proposed replacements: box H/ACA snoRNA binding telomerase RNA binding Supporting Evidence: PMID:10591218 also with human telomerase RNA |
| GO:0005515 protein binding | IPI PMID:16601202 hNaf1 is required for accumulation of human box H/ACA snoRNP... | KEEP AS NON CORE | Summary: NAF1 associates with dyskerin during H/ACA RNP assembly. Reason: The original human HeLa experiments recover endogenous dyskerin with NAF1 using an antibody-control comparison. The association is positive, but this source does not demonstrate a direct purified interface or justify a protein-folding-chaperone binding class. Retain this assembly-associated binding under the scoped project instruction for supported generic interactions. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16618814 Stepwise RNP assembly at the site of H/ACA RNA transcription... | KEEP AS NON CORE | Summary: NAF1 recruits and binds dyskerin during nascent H/ACA assembly. Reason: The source combines translated-protein immunoprecipitation, NAF1/GAR1 competition and human U2OS tethering that recruits endogenous NAP57/dyskerin. Rat reporter RNA and historical NAP57 constructs are kept distinct from present human product coordinates. NAF1 is an RNP assembly factor; this does not by itself establish the stricter protein-folding chaperone class. Retain the positive generic association as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18358808 Identification of ATPases pontin and reptin as telomerase co... | MODIFY | Summary: Dyskerin associates with the ATPase RUVBL1. Reason: The original includes RNase-resistant human co-immunoprecipitation and binding between recombinant MBP-dyskerin and pontin/RUVBL1. RUVBL1 has independently established ATPase activity, so ATPase binding is a supported partner-class refinement. It does not assert ATP hydrolysis by dyskerin, activation of RUVBL1, or a purified direct interface for the AP-MS observations. Proposed replacements: ATPase binding |
| GO:0005515 protein binding | IPI PMID:19179534 A human telomerase holoenzyme protein required for Cajal bod... | KEEP AS NON CORE | Summary: NAF1 is recovered in a human dyskerin assembly complex. Reason: The original dyskerin affinity purification identifies NAF1, and its association persists after RNase treatment. The experiment supports an assembly-associated interaction without establishing NAF1 as a protein-folding chaperone. Keep the positive generic interaction as non-core under the project instruction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19179534 A human telomerase holoenzyme protein required for Cajal bod... | KEEP AS NON CORE | Summary: TCAB1 associates with dyskerin-containing telomerase RNP. Reason: The original human dyskerin purification and reciprocal TCAB1 work support this association. TCAB1 organizes and chaperones RNA, but that is not the protein-folding chaperone class defined by GO:0051087. A generic positive RNP interaction is retained as non-core without assigning a new molecular mechanism to DKC1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19179534 A human telomerase holoenzyme protein required for Cajal bod... | MODIFY | Summary: Dyskerin associates with the ATPase RUVBL1. Reason: Endogenous-replacement human dyskerin purification recovers pontin/RUVBL1 after RNase treatment. RUVBL1 has independently established ATPase activity, so ATPase binding is a supported partner-class refinement. It does not assert ATP hydrolysis by dyskerin, activation of RUVBL1, or a purified direct interface for the AP-MS observations. Proposed replacements: ATPase binding |
| GO:0005515 protein binding | IPI PMID:19383767 SHQ1 is required prior to NAF1 for assembly of H/ACA small n... | KEEP AS NON CORE | Summary: SHQ1 binds free dyskerin before mature H/ACA RNP assembly. Reason: Recombinant SHQ1 and MBP-NAP57/dyskerin directly associate, and the original distinguishes RNA-free dyskerin from assembled RNPs. SHQ1 is proposed to stabilize an assembly-competent protein; these observations do not establish all requirements of protein-folding chaperone activity. Retain the direct positive interaction as non-core rather than infer that class from assembly-factor terminology. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21846770 The DEAH-box RNA helicase RHAU binds an intramolecular RNA G... | KEEP AS NON CORE | Summary: Dyskerin and DHX36 associate through a telomerase-RNA-dependent RNP. Reason: Human HEK293T co-immunoprecipitation recovers DHX36/RHAU with dyskerin when wild-type TERC is present, whereas disruption of the TERC G-quadruplex reduces association. This is positive, RNA-dependent co-complex evidence. Although DHX36 is an ATP-dependent helicase, this source does not independently establish recognition of the helicase protein by dyskerin; retain generic binding as non-core rather than infer an ATPase-binding interface or catalytic regulation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23685356 HOT1 is a mammalian direct telomere repeat-binding protein c... | KEEP AS NON CORE | Summary: Dyskerin is recovered with the telomere-binding protein HOT1/HMBOX1. Reason: Human HeLa HOT1 immunoprecipitation/SILAC and associated assays identify dyskerin and other H/ACA components. HOT1 directly binds telomeric DNA; a homeobox domain alone does not establish a transcription-factor role for this source interaction. Retain the supported association as non-core without inventing a transcriptional or direct binding mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24965446 Host factors that interact with the pestivirus N-terminal pr... | KEEP AS NON CORE | Summary: Dyskerin is recovered in a viral Npro-associated ribonucleoprotein fraction. Reason: GST-Npro affinity capture from human HEK293 lysate identifies O60832 in Table 1 with a GST control. The imported partner is the processed viral leader protease, but the authors explicitly note that the RNP interactions may be indirect. No independent binary dyskerinβNpro binding experiment was identified. Retain the positive co-complex association as non-core without asserting protease recognition, DKC1 cleavage or a native human complex. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: Dyskerin is recovered in a TCAB1 affinity-purified complex. Reason: The literal human TCAB1-bait AP-MS record and the primary study support the association. The paper demonstrates TRiC-dependent folding of TCAB1, not TCAB1 acting as a protein-folding chaperone for dyskerin. Keep the positive RNP interaction as non-core without transferring the TRiC catalytic/client role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: NAF1 affinity purification recovers dyskerin in human cells. Reason: The source-specific IntAct record identifies NAF1 as a tagged bait and DKC1 as a prey in HeLa affinity-capture mass spectrometry, with the source table and clone recorded. The complete original experimental controls were not independently recovered; positive curated pair evidence and established NAF1 assembly biology support conservative non-core retention. No direct interface or narrower folding-chaperone class is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: SHQ1 is recovered with dyskerin in an assembly-associated complex. Reason: The literal source-specific 2017 BioPlex human HEK293T dyskerin-bait AP-MS records support this positive association. Bait/prey identity, tag features and sequence/taxon hashes were checked without converting gene-level proteomics into a natural-product claim. SHQ1 assembly/stability functions do not alone establish the stricter protein-folding-chaperone class; retain generic binding as non-core, without asserting a direct interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: NAF1 is recovered with dyskerin in an assembly-associated complex. Reason: The literal source-specific 2017 BioPlex human HEK293T dyskerin-bait AP-MS records support this positive association. Bait/prey identity, tag features and sequence/taxon hashes were checked without converting gene-level proteomics into a natural-product claim. NAF1 assembly/stability functions do not alone establish the stricter protein-folding-chaperone class; retain generic binding as non-core, without asserting a direct interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Dyskerin associates with the ATPase RUVBL1. Reason: The literal BioPlex record recovers dyskerin with RUVBL1 bait in HEK293T cells, using C-terminal affinity tags. RUVBL1 has independently established ATPase activity, so ATPase binding is a supported partner-class refinement. It does not assert ATP hydrolysis by dyskerin, activation of RUVBL1, or a purified direct interface for the AP-MS observations. Proposed replacements: ATPase binding |
| GO:0005515 protein binding | IPI PMID:29178645 Inherited SHQ1 mutations impair interaction with NAP57/dyske... | KEEP AS NON CORE | Summary: SHQ1 mutations affect its direct association with dyskerin. Reason: The original recombinant assays compare wild-type and R335C/A426V SHQ1 constructs for binding to MBP-NAP57/dyskerin, with reduced but retained binding. Structural interpretation from yeast is separate from the human binding experiment. This supports SHQ1 association, without establishing a protein-folding activity of the partner; retain as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: SHQ1 is recovered with dyskerin in an assembly-associated complex. Reason: The literal source-specific 2021 BioPlex dyskerin-bait records in HEK293T and HCT116 records support this positive association. Bait/prey identity, tag features and sequence/taxon hashes were checked without converting gene-level proteomics into a natural-product claim. SHQ1 assembly/stability functions do not alone establish the stricter protein-folding-chaperone class; retain generic binding as non-core, without asserting a direct interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: NAF1 is recovered with dyskerin in an assembly-associated complex. Reason: The literal source-specific 2021 BioPlex dyskerin-bait records in HEK293T and HCT116 records support this positive association. Bait/prey identity, tag features and sequence/taxon hashes were checked without converting gene-level proteomics into a natural-product claim. NAF1 assembly/stability functions do not alone establish the stricter protein-folding-chaperone class; retain generic binding as non-core, without asserting a direct interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Dyskerin associates with the ATPase RUVBL1. Reason: The literal 2021 BioPlex record recovers dyskerin with RUVBL1 bait in HEK293T cells; source pair, publication and record index were checked together. RUVBL1 has independently established ATPase activity, so ATPase binding is a supported partner-class refinement. It does not assert ATP hydrolysis by dyskerin, activation of RUVBL1, or a purified direct interface for the AP-MS observations. Proposed replacements: ATPase binding |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: Endogenously tagged dyskerin recovers NAF1 in OpenCell. Reason: The actual OpenCell table contains the human DKC1-bait/NAF1-prey pair. The study uses CRISPR endogenous tagging and triplicate affinity capture from HEK293T cells. This is a co-complex observation, with proteomic accession-group ambiguity preserved; it does not identify a particular NAF1 isoform or demonstrate a purified interface. Keep the assembly-associated interaction as non-core. Supporting Evidence: |
| GO:0005634 nucleus | IDA GO_REF:0000054 | MODIFY | Summary: Nuclear dyskerin occupies nucleoplasmic and nucleolar pools. Reason: The expressed-fusion source supports nuclear residence. The human localization study and HPA record establish nucleoplasm and nucleolus as more informative locations, with temporal movement and nonexclusive pools. The refinement does not imply that every observed nuclear molecule is simultaneously in both subcompartments. Cajal body is itself part of nucleoplasm in the typed ontology, so the separately supported Cajal-body pool is covered without adding a nested replacement or excluding diffuse nucleoplasm. Proposed replacements: nucleoplasm nucleolus |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Dyskerin has a nucleoplasmic pool. Reason: The inspected HPA target record reports supported nucleoplasm alongside fibrillar-center localization. This is consistent with nucleoplasmic H/ACA/telomerase assembly; it does not imply an exclusively diffuse pool or resolve natural products. Supporting Evidence: GO_REF:0000052 |
| GO:0005654 nucleoplasm | TAS PMID:10556300 Dyskerin localizes to the nucleolus and its mislocalization ... | ACCEPT | Summary: Human dyskerin accumulates first in nucleoplasm before nucleoli. Reason: The complete cached abstract explicitly reports time-dependent localization of expressed human EGFP-dyskerin to nucleoplasm and then nucleoli, with occasional coiled-body staining. Full original access was unavailable; the specific positive observation and independent HPA evidence support retention with curator deference. Supporting Evidence: |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-163090 | ACCEPT | Summary: Dyskerin remains in the nucleoplasmic telomerase RNP during initial telomeric repeat extension. Reason: The curated event adds nucleotides to the telomeric DNA end using the TERC template. Its bound telomerase input, output and catalytic complex contain DKC1 2β514; TERT supplies DNA synthesis, while dyskerin is an RNA-associated structural subunit. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-163090 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-163096 | ACCEPT | Summary: A DKC1-containing telomerase RNP is recruited to a telomeric chromosome end. Reason: The curated recruitment event connects free telomerase RNP to the chromosome-bound RNP. Both contain DKC1 2β514 in nucleoplasm; this does not establish a separate DKC1 DNA-recruitment activity. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-163096 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-163099 | ACCEPT | Summary: Dyskerin is retained during alignment of the telomerase RNA template with the chromosome end. Reason: The curated alignment event converts a telomere-associated telomerase RNP into a base-paired complex. Both contain DKC1 2β514 in nucleoplasm; RNAβDNA template alignment is a property of the complete RNP, not an autonomous dyskerin reaction. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-163099 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-163120 | ACCEPT | Summary: Dyskerin remains in the telomerase RNP after its dissociation from the chromosome end. Reason: The curated event releases telomerase RNP from an extended chromosome end. DKC1 2β514 occurs in both bound input and released RNP in nucleoplasm; membership does not make dyskerin an independent dissociation enzyme. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-163120 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-164616 | ACCEPT | Summary: Dyskerin joins the nucleoplasmic telomerase RNP during its biogenesis. Reason: The curated assembly event includes DKC1 2β514 as an input and a component of the assembled telomerase RNP. H/ACA binding supports TERC accumulation and RNP assembly; the source also describes nuclear trafficking without assigning every assembly step to one exclusive subcompartment. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-164616 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-164617 | ACCEPT | Summary: Dyskerin remains in telomerase during a further round of telomeric repeat extension. Reason: The curated subsequent-extension event contains DKC1 2β514 in chromosome-bound telomerase input, product and catalytic complexes in nucleoplasm. This is continued RNP membership; TERT, not dyskerin, performs nucleotide polymerization. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-164617 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-164620 | ACCEPT | Summary: A DKC1-containing telomerase RNP translocates and realigns its RNA template for another repeat. Reason: The curated translocation event connects an extended telomere-associated RNP to the next base-paired state. Both contain DKC1 2β514 in nucleoplasm; the model does not assign an autonomous motor or translocase activity to dyskerin. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-164620 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6790905 | ACCEPT | Summary: Dyskerin is the catalytic subunit of a guide-directed pre-rRNA-modifying H/ACA particle. Reason: The curated event converts uridine to pseudouridine in pre-rRNA using an H/ACA guide RNA. Its catalytic physical entity contains DKC1 2β514 and is modeled in nucleoplasm; that curated compartment is retained without excluding the independently supported nucleolar pool. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-6790905 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9671145 | ACCEPT | Summary: SHQ1 binds dyskerin in an early nucleoplasmic RNP-assembly intermediate. Reason: The curated binding event takes DKC1 2β514 as input and produces a DKC1:SHQ1 complex in nucleoplasm. SHQ1 binding controls stepwise H/ACA/telomerase assembly and does not imply that SHQ1 is a permanent mature telomerase subunit. The inspected positive path ends at reference O60832; it is curated event evidence, not a new localization experiment. Supporting Evidence: Reactome:R-HSA-9671145 |
| GO:0005697 telomerase holoenzyme complex | IDA PMID:12135483 Differential regulation of telomerase activity by six telome... | ACCEPT | Summary: Dyskerin is a component of telomerase holoenzyme. Reason: PMID:12135483 explicitly studies dyskerin among telomerase components. Its full text was unavailable, but later human purification and structural studies independently establish whole-holoenzyme membership. This component assertion is distinct from intrinsic reverse-transcriptase activity. |
| GO:0005697 telomerase holoenzyme complex | IDA PMID:18082603 Purification of human telomerase complexes identifies factor... | ACCEPT | Summary: Human telomerase purifications recover dyskerin. Reason: The original human hTERT/hTR and dyskerin purification experiments establish dyskerin within telomerase RNPs. H/ACA-RNP stability and telomerase assembly are supported without treating every associated factor as a permanent catalytic subunit. Supporting Evidence: |
| GO:0005697 telomerase holoenzyme complex | IDA PMID:29695869 Cryo-EM structure of substrate-bound human telomerase holoen... | ACCEPT | Summary: Dyskerin is a physical component of active human telomerase holoenzyme. Reason: PMID:29695869 reconstitutes human telomerase by expressing TERT and hTR in human cells, identifies endogenous dyskerin in purified active fractions, and places two dyskerin-containing H/ACA heterotetramers in the H/ACA lobe. Immunoblotting, mass spectrometry, subunit-dropout comparisons and cryo-EM support whole-holoenzyme membership. The catalytic TERTβRNA lobe is distinct; neither holoenzyme membership nor primer extension is evidence that dyskerin itself performs reverse transcription. At 8.2 Γ
for the H/ACA lobe, the interpretation uses fitted homologous structures rather than an atomic-resolution human dyskerin structure. Supporting Evidence: |
| GO:0005697 telomerase holoenzyme complex | NAS PMID:20351177 Specificity and stoichiometry of subunit interactions in the... | ACCEPT | Summary: Dyskerin is an assembled human telomerase subunit. Reason: The cited original uses controlled tandem-tag purification and RNA/protein measurements to establish dyskerin-containing H/ACA RNPs on human telomerase RNA. Retain whole-holoenzyme membership while preserving assembly heterogeneity and avoiding autonomous polymerase claims. Supporting Evidence: |
| GO:0005697 telomerase holoenzyme complex | TAS PMID:20351177 Specificity and stoichiometry of subunit interactions in the... | ACCEPT | Summary: Dyskerin is an assembled human telomerase subunit. Reason: The cited original uses controlled tandem-tag purification and RNA/protein measurements to establish dyskerin-containing H/ACA RNPs on human telomerase RNA. Retain whole-holoenzyme membership while preserving assembly heterogeneity and avoiding autonomous polymerase claims. Supporting Evidence: |
| GO:0005730 nucleolus | IEA GO_REF:0000120 | ACCEPT | Summary: Conserved dyskerin occupies nucleoli. Reason: The actual mouse ortholog donor and Swiss-Prot location mapping support nucleolar residence. PMID:23726835 directly compares wild-type and D125A mouse dyskerin in nucleoli/Cajal bodies; human EGFP-dyskerin localization independently corroborates nucleoli. The mutant catalytic/stability phenotype is not transferred as a normal human product property. |
| GO:0005730 nucleolus | TAS PMID:10556300 Dyskerin localizes to the nucleolus and its mislocalization ... | ACCEPT | Summary: Human dyskerin localizes to nucleoli. Reason: The complete human source abstract explicitly reports nucleolar enrichment after an initial nucleoplasmic phase. Full original access was unavailable, but direct HPA fibrillar-center evidence and H/ACA biology corroborate the location without forcing all dyskerin into one nucleolar substructure. Supporting Evidence: |
| GO:0005737 cytoplasm | EXP PMID:21820037 A new human dyskerin isoform with cytoplasmic localization. | KEEP AS NON CORE | Summary: A natural shorter dyskerin product has experimentally reported cytoplasmic localization. Reason: The PMID:21820037 abstract explicitly describes a human splice variant, protein detection by immunoblotting and immunocytochemistry, and cytoplasmic localization. Official UniProt connects this study to VSP_042422 and O60832-2, named isoform 3; sequence reconstruction gives 420 residues. The location is therefore retained despite unavailable full-text assay details. It is not generalized to every product, refined to cytosol without fraction-specific evidence, or converted into a separate catalytic core from the reported HeLa overexpression phenotypes. Supporting Evidence: PMID:21820037 variant dyskerin with unexpected cytoplasmic localization |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A characterized alternative dyskerin product can occupy cytoplasm. Reason: The Swiss-Prot subcellular-location mapping is consistent with the reported cytoplasmic alternative product in PMID:21820037. This is a real non-core pool rather than a localization contradiction. The source does not establish exclusive cytosol, normal catalytic equivalence or a separate cytoplasmic mechanism for all products. |
| GO:0006364 rRNA processing | TAS PMID:10556300 Dyskerin localizes to the nucleolus and its mislocalization ... | ACCEPT | Summary: Dyskerin participates in rRNA maturation through H/ACA RNP function. Reason: The original human localization report motivates rRNA-processing involvement; its full text was unavailable. Conserved H/ACA assembly and human rRNA modification, together with direct yeast and mouse processing experiments, support this biologically correct broader maturation role. It is not an assertion that dyskerin cleaves pre-rRNA. |
| GO:0006396 RNA processing | IEA GO_REF:0000002 | MODIFY | Summary: The predicted RNA-processing role includes defined H/ACA-dependent maturation. Reason: The actual IPR002501 and IPR004802 memberships match dyskerin/Cbf5 RNA-processing biology. rRNA processing is an established narrower process supported by H/ACA assembly and modification evidence; the refinement does not assign an endoribonuclease mechanism. The inherited snRNA pseudouridylation role is also a descendant of RNA processing and is supported by the literal Cbf5 lineage and the original yeast U2 guide-dependent/catalytic controls in PMID:15962000. Include it alongside rRNA processing; the separately retained mRNA pseudouridylation term is not an is_a/part_of descendant of this broad processing term. Proposed replacements: rRNA processing snRNA pseudouridine synthesis |
| GO:0006396 RNA processing | TAS PMID:9590285 X-linked dyskeratosis congenita is caused by mutations in a ... | MODIFY | Summary: The early human disease-gene report supports a conserved rRNA-processing function. Reason: PMID:9590285 identifies the human dyskeratosis-congenita gene and conserved TruB/Cbf5 features rather than directly measuring every RNA process. Later target and ortholog evidence establishes rRNA maturation, providing a supported narrower replacement while preserving the early source and its inference limits. The inherited snRNA pseudouridylation role is also a descendant of RNA processing and is supported by the literal Cbf5 lineage and the original yeast U2 guide-dependent/catalytic controls in PMID:15962000. Include it alongside rRNA processing; the separately retained mRNA pseudouridylation term is not an is_a/part_of descendant of this broad processing term. Proposed replacements: rRNA processing snRNA pseudouridine synthesis |
| GO:0007004 telomere maintenance via telomerase | IDA PMID:29695869 Cryo-EM structure of substrate-bound human telomerase holoen... | ACCEPT | Summary: The dyskerin-containing H/ACA RNP structurally contributes to active telomerase. Reason: The active human holoenzyme isolated in PMID:29695869 contains dyskerin at hTR-binding and H/ACA-subunit interfaces, whereas TERT occupies the catalytic lobe. Direct primer-extension assays establish activity of the assembled complex. Dyskerin performs RNA-binding and structural work within that complex, supporting participation in telomerase-dependent telomere maintenance without claiming it is the polymerase. The HCT116 telomere-rescue controls test tagged TERT, not an isolated DKC1 rescue; this distinction is retained. Supporting Evidence: |
| GO:0007004 telomere maintenance via telomerase | IMP PMID:26950371 Inhibition of telomerase RNA decay rescues telomerase defici... | ACCEPT | Summary: Dyskerin maintains telomerase by protecting its RNA component. Reason: In human HeLa cells, DKC1 depletion destabilizes hTR; inhibiting nuclear and cytoplasmic decay pathways restores hTR abundance, localization and telomerase activity. This supports participation through RNA binding/stabilization and assembled RNP function, not autonomous telomeric DNA synthesis. Supporting Evidence: |
| GO:0007004 telomere maintenance via telomerase | NAS PMID:20351177 Specificity and stoichiometry of subunit interactions in the... | ACCEPT | Summary: The human dyskerin-containing RNP supports telomere maintenance. Reason: The source demonstrates assembly of two dyskerin-containing H/ACA units on hTR in active telomerase. Together with direct target RNA-stability evidence, this supports the established telomere-maintenance role; it does not require dyskerin to be the reverse transcriptase. |
| GO:0007004 telomere maintenance via telomerase | TAS PMID:10591218 A telomerase component is defective in the human disease dys... | ACCEPT | Summary: Dyskerin supports telomerase RNA abundance and telomerase-dependent telomere maintenance. Reason: PMID:10591218 explicitly reports dyskerinβhTR association and lower hTR, telomerase activity and telomere length in patient-derived fibroblasts and lymphoblasts. Its full original was not recovered, so detailed assay or mutant-construct claims are not added. The independently read human structure in PMID:29695869 shows the physical RNA-binding/structural contribution that complements these cellular observations. The existing TAS process annotation is retained with curator deference; dyskerin is not assigned TERT chemistry. Supporting Evidence: |
| GO:0009451 RNA modification | IEA GO_REF:0000002 | MODIFY | Summary: Dyskerin modifies specific RNA classes by pseudouridylation. Reason: The actual IPR020103 mapping supports RNA modification, while human rRNA/mRNA and conserved guide-dependent snRNA evidence identify the chemistry and substrates. Replace the broad modification term with supported pseudouridylation processes without assigning additional chemical modifications. Proposed replacements: snoRNA guided rRNA pseudouridine synthesis snRNA pseudouridine synthesis mRNA pseudouridine synthesis |
| GO:0009982 pseudouridine synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Pseudouridine synthase activity is conserved on the DKC1 lineage. Reason: The literal IBD at PTN000565614 is ancestral to human DKC1 and has experimental human and yeast grounding. The target itself is a valid descendant source, not circular evidence. Human rRNA and mRNA modification supports the general synthase term, while yeast assays independently establish H/ACA pseudouridylation. |
| GO:0009982 pseudouridine synthase activity | IEA GO_REF:0000002 | ACCEPT | Summary: The conserved catalytic domain supports pseudouridine synthase activity. Reason: The verified IPR020103 membership and its literal GO mapping agree with dyskerin catalytic chemistry. Retain the general enzyme activity because target evidence spans more than rRNA; this does not attribute catalytic equivalence to the shortened natural product. |
| GO:0009982 pseudouridine synthase activity | IMP PMID:25219674 Transcriptome-wide mapping reveals widespread dynamic-regula... | ACCEPT | Summary: Dyskerin supports pseudouridine formation in more than one RNA substrate class. Reason: PMID:25219674 measures reduced rRNA pseudouridylation after human DKC1 knockdown and lower modification at 58 of 396 mapped mRNA/non-rRNA sites, with snoRNA complementarity among the DKC1-dependent sites. The general RNA-isomerization term fits the combined substrate scope; replacing it solely with rRNA activity would lose the mRNA evidence. These cellular perturbation data support the existing IMP, while not being described as purified DKC1 kinetics or proof of modification of every RNA species. The H/ACA catalytic assignment is also established in the official protein record. Supporting Evidence: |
| GO:0015030 Cajal body | IEA GO_REF:0000120 | ACCEPT | Summary: Dyskerin is present in Cajal bodies as well as nucleoli. Reason: The current ARBA rule matches a mammalian dyskerin FunFam branch, and the actual mouse donor record is supported by wild-type/mutant localization experiments showing Cajal bodies and nucleoli. Human source observations of coiled bodies corroborate this nonexclusive pool. Rule membership is not substituted for the localization evidence. |
| GO:0031118 rRNA pseudouridine synthesis | IBA GO_REF:0000033 | MODIFY | Summary: The conserved rRNA modification role is refined to the supported snoRNA-guided mechanism. Reason: The literal PTN000565614 IBD lies on the human lineage and supports the broad ancestral rRNA-pseudouridylation claim. Its rat, yeast, mouse and human descendant evidence remains valid; human self-grounding is not circular. Human H/ACA-dependent modification and rat guide-dependent assays establish snoRNA-guided rRNA pseudouridylation for the target, so GO:0000454 is the supported narrower replacement. This target-level refinement does not relabel the entire ArchaeaβEukaryota ancestral clade as snoRNA-guided. PMID:15240872 adds mouse mutation evidence for rRNA pseudouridylation, with distinct telomerase effects of A353V and G402E. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000565614 Β· PTN000565614 SUPPORTS TRANSFER The literal rRNA-pseudouridylation IBD is on the human lineage and has experimental descendant grounding. The source supports transfer; the narrower snoRNA-guided target term follows human and mammalian H/ACA evidence, without changing the broad ancestral assertion. Proposed replacements: snoRNA guided rRNA pseudouridine synthesis |
| GO:0031118 rRNA pseudouridine synthesis | IEA GO_REF:0000117 | MODIFY | Summary: The matched mammalian rule is refined to the established snoRNA-guided rRNA reaction. Reason: The actual ARBA00026725 branch requiring the dyskerin FunFam and Mammalia matches the target and soundly supports rRNA pseudouridylation. Human DKC1/H/ACA evidence and guide-dependent mammalian particles establish the narrower snoRNA-guided process, GO:0000454, a descendant of GO:0031118. Refining the target does not invalidate the rule's broader mapping or imply a 5S-rRNA-specific substrate. Proposed replacements: snoRNA guided rRNA pseudouridine synthesis |
| GO:0031120 snRNA pseudouridine synthesis | IBA GO_REF:0000033 | ACCEPT | Summary: H/ACA dyskerin supports guide-dependent snRNA pseudouridylation. Reason: The PTN000565614 IBD is on the target lineage and is grounded by the yeast Cbf5 U2 Ξ¨42 experiment. The original shows Cbf5-containing purified complexes, loss after RNA digestion, guide-RNA rescue and catalytic/depletion controls. This is a genuine ancestral catalytic function consistent with human H/ACA scaRNP membership, not a claim that the yeast U2 assay used human DKC1. |
| GO:0031429 box H/ACA snoRNP complex | IBA GO_REF:0000033 | ACCEPT | Summary: Dyskerin is the catalytic protein in H/ACA snoRNPs. Reason: The literal PTN000565615 eukaryotic IBD lies on the human lineage and has yeast, rat and human experimental grounding. Target RNP purification independently corroborates membership. Retain the ancestral complex assertion without using donor number or the target appearing among sources as a criticism. |
| GO:0031429 box H/ACA snoRNP complex | IDA PMID:18082603 Purification of human telomerase complexes identifies factor... | ACCEPT | Summary: Human dyskerin associates with H/ACA snoRNA-containing particles. Reason: The original human dyskerin purification recovers U64 as well as hTR, and depletion affects H/ACA RNA stability. U64 association grounds the snoRNP claim separately from telomerase RNP membership. Supporting Evidence: |
| GO:0031429 box H/ACA snoRNP complex | TAS PMID:22527283 An enhanced H/ACA RNP assembly mechanism for human telomeras... | ACCEPT | Summary: Dyskerin is a constituent of H/ACA snoRNPs. Reason: The original distinguishes preassembled dyskerin/NHP2/NAF1 assembly complexes from mature GAR1-containing particles and studies RNA recruitment. Established H/ACA snoRNP membership is supported; the preassembly proteins should not all be treated as permanent mature-complex components. Supporting Evidence: |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IDA PMID:23685356 HOT1 is a mammalian direct telomere repeat-binding protein c... | KEEP AS NON CORE | Summary: Dyskerin-containing active telomerase supports a positive telomere-maintenance context. Reason: The HOT1 study recovers dyskerin and uses dyskerin immunoprecipitates as a positive active-telomerase control. Its principal recruitment and depletion experiments concern HOT1/TCAB1, so they are not described as DKC1-specific perturbations. The positive regulatory context is retained conservatively alongside the established DKC1 RNA-stabilizing subunit role, rather than presented as a distinct autonomous regulator. |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: Dyskerin supports telomerase recruitment and new repeat addition. Reason: The original human DKC1-depletion controls show impaired TERC accumulation/localization, telomerase recruitment and newly synthesized telomeric repeats. These support a positive regulatory consequence of its structural/RNA-stabilizing role. Retain the process as non-core instead of inventing a separate regulatory mechanism. Supporting Evidence: |
| GO:0034513 box H/ACA snoRNA binding | IPI PMID:18082603 Purification of human telomerase complexes identifies factor... | ACCEPT | Summary: Dyskerin associates with the H/ACA snoRNA U64/SNORA64. Reason: The original human dyskerin RNP purification recovers U64, and the literal RNAcentral source URS0000210FD6 identifies SNORA64. This supports box H/ACA snoRNA binding in an assembled RNP without a purified monomer affinity claim. Supporting Evidence: |
| GO:0070034 telomerase RNA binding | IPI PMID:18082603 Purification of human telomerase complexes identifies factor... | ACCEPT | Summary: Dyskerin binds telomerase RNA within H/ACA RNP. Reason: Human affinity-purified dyskerin RNPs contain hTR and are sensitive to loss of H/ACA assembly components. Retain the specific RNA-binding activity without assigning an isolated-protein dissociation constant or an unverified historical construct to a current natural isoform. Supporting Evidence: |
| GO:0070034 telomerase RNA binding | IPI PMID:20351177 Specificity and stoichiometry of subunit interactions in the... | ACCEPT | Summary: Dyskerin binds telomerase RNA within H/ACA RNP. Reason: Controlled human tandem-tag purification establishes dyskerin-containing H/ACA units assembled on hTR. Retain the specific RNA-binding activity without assigning an isolated-protein dissociation constant or an unverified historical construct to a current natural isoform. Supporting Evidence: |
| GO:0070034 telomerase RNA binding | IPI PMID:22527283 An enhanced H/ACA RNP assembly mechanism for human telomeras... | ACCEPT | Summary: Dyskerin binds telomerase RNA within H/ACA RNP. Reason: Human dyskerin-containing preassembled complexes recruit the hTR 3β² hairpin through H/ACA/BIO elements. Retain the specific RNA-binding activity without assigning an isolated-protein dissociation constant or an unverified historical construct to a current natural isoform. Supporting Evidence: |
| GO:0070034 telomerase RNA binding | IPI PMID:26950371 Inhibition of telomerase RNA decay rescues telomerase defici... | ACCEPT | Summary: Dyskerin binds telomerase RNA within H/ACA RNP. Reason: Human dyskerin RNA-binding mutants and depletion/decay-rescue experiments link hTR association to its stability. Retain the specific RNA-binding activity without assigning an isolated-protein dissociation constant or an unverified historical construct to a current natural isoform. Supporting Evidence: |
| GO:0072589 box H/ACA scaRNP complex | TAS PMID:22527283 An enhanced H/ACA RNP assembly mechanism for human telomeras... | ACCEPT | Summary: Dyskerin is a shared H/ACA scaRNP constituent. Reason: The source places dyskerin in the conserved H/ACA core shared by scaRNAs, snoRNAs and telomerase RNA; independent human dyskerin purification recovers H/ACA scaRNAs. The Cajal-body scaRNP class is distinct from the telomerase subcomplex and does not imply that all dyskerin particles contain every RNA class. |
| GO:0090661 box H/ACA telomerase RNP complex | IDA PMID:18082603 Purification of human telomerase complexes identifies factor... | ACCEPT | Summary: Dyskerin belongs to the H/ACA telomerase RNP subcomplex. Reason: Human telomerase/dyskerin purification and hTR association support this specific structural RNP. Its H/ACA proteins stabilize telomerase RNA; this complex is not assigned pseudouridylation of hTR or autonomous DNA synthesis. Supporting Evidence: |
| GO:0090661 box H/ACA telomerase RNP complex | TAS PMID:22527283 An enhanced H/ACA RNP assembly mechanism for human telomeras... | ACCEPT | Summary: The hTR H/ACA hairpin recruits a dyskerin-containing assembly complex. Reason: The source directly studies recruitment of the human preassembled H/ACA complex to the telomerase RNA 3β² hairpin. Preserve its assembly-factor versus mature-particle distinctions while retaining the defined H/ACA telomerase RNP membership. Supporting Evidence: |
| GO:0090666 scaRNA localization to Cajal body | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | UNDECIDED | Summary: The DKC1-specific scaRNA localization assertion remains unresolved. Reason: The main original demonstrates human DKC1-dependent TERC abundance/localization, but the scaRNA experiments visible in the main text primarily address TRiC/TCAB1. The source-specific DKC1 observations for the three imported scaRNA inputs could not be adjudicated because the linked supplement was not recovered as scientific content. Preserve the positive curator assertion without converting TERC experiments into scaRNA evidence or claiming the experiments were absent. Supporting Evidence: |
| GO:0090669 telomerase RNA stabilization | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | ACCEPT | Summary: Dyskerin stabilizes human telomerase RNA. Reason: The human DKC1-knockdown controls in this source reduce overall TERC accumulation rather than merely redistributing it. Independent decay assays and pathway rescue in PMID:26950371 directly corroborate stabilization. This is an RNA-bound structural contribution, not just a generic essentiality inference. |
| GO:0090669 telomerase RNA stabilization | IMP PMID:26950371 Inhibition of telomerase RNA decay rescues telomerase defici... | ACCEPT | Summary: Dyskerin protects telomerase RNA from degradation. Reason: The original uses human HeLa DKC1 depletion, actinomycin-D decay measurements and nuclear/cytoplasmic decay-pathway rescue. The evidence supports protection of bound hTR and explains reduced telomerase activity without assigning reverse-transcriptase chemistry to dyskerin. Supporting Evidence: PMID:26950371 we observed that in dyskerin knockdown cells, hTR was degraded faster than in control cells |
| GO:0120159 rRNA pseudouridine synthase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Dyskerin catalyzes uridine isomerization in rRNA. Reason: The literal Rhea mapping originates from the UniProt reaction phrased with 5S rRNA, whereas GO:0120159 defines rRNA pseudouridine synthase activity generally. Human DKC1-dependent rRNA modification and H/ACA biochemical evidence support this general rRNA enzyme activity. A 5S-specific target reaction is not established by the inspected human experiments and is not asserted here. |
| GO:1904867 protein localization to Cajal body | HMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | UNDECIDED | Summary: DKC1-dependent TCAB1 protein localization requires source-specific resolution. Reason: The original main text establishes TCAB1 folding by TRiC and includes DKC1 controls for TERC abundance/recruitment. The imported HMP assertion specifically concerns TCAB1 protein localization to Cajal bodies. Its target-specific screen/supplemental evidence was not independently accessible, so neither the positive TERC result nor the TRiC folding experiments settle this distinct claim. Preserve the curated observation as unresolved, not false. Supporting Evidence: |
| GO:1904872 regulation of telomerase RNA localization to Cajal body | IMP PMID:26950371 Inhibition of telomerase RNA decay rescues telomerase defici... | KEEP AS NON CORE | Summary: Dyskerin-dependent RNA stability affects TERC localization to Cajal bodies. Reason: The original human depletion and decay-pathway-rescue experiments show loss and restoration of Cajal-body hTR. DKC1 RNA binding/stabilization supplies a mechanistic basis, while degradation-pathway rescue shows that DKC1 is not uniquely responsible for transport. Retain this contextual regulatory process without inventing a separate trafficking activity. Supporting Evidence: |
| GO:1904874 positive regulation of telomerase RNA localization to Cajal body | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: Dyskerin supports accumulation of TERC in Cajal bodies. Reason: Human DKC1-depletion controls strongly reduce TERC-positive Cajal bodies in the primary screen and follow-up. The accompanying global TERC loss distinguishes this from the TCAB1/TRiC nucleolar-mislocalization phenotype. Retain the positive localization consequence of RNA stabilization without assigning a transport motor or chaperone activity. Supporting Evidence: |
| GO:1990481 mRNA pseudouridine synthesis | IBA GO_REF:0000033 | ACCEPT | Summary: Dyskerin has an inherited mRNA pseudouridylation role. Reason: The literal PTN000565614 IBD is on the human lineage and is grounded by experimental yeast Cbf5 annotations, including PMID:25219674. That paper also directly identifies human DKC1-dependent mRNA modification. The independent 25192136 study reports snoRNA-target-compatible mRNA sites; it is not represented as a purified human DKC1 assay. The convergent target and lineage evidence supports retention. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Does the 420-residue cytoplasmic product retain catalytic activity or assemble with distinct RNA/protein partners under endogenous expression?
Q: Which DKC1-specific supplemental observations establish scaRNA and TCAB1-protein localization effects beyond the documented TERC-stability phenotype?
Q: Which human mRNA sites are directly modified by dyskerin-containing RNPs, and which guide RNAs and cellular pools specify those sites?
Q: Does the curated 5S-rRNA reaction description reflect direct DKC1 substrate evidence, or should the reaction context remain rRNA-general?
Experiment: Compare purified, sequence-verified 514- and 420-residue products in matched H/ACA RNP reconstitution assays, measuring RNA binding and site-specific pseudouridine formation separately.
Hypothesis: Loss of the canonical C terminus changes localization and assembly without necessarily abolishing the retained catalytic domain.
Experiment: Use endogenous isoform-resolved tagging with RNA-protein crosslinking and site-resolved pseudouridine mapping to connect cytoplasmic and nuclear DKC1 pools to actual RNA substrates.
Hypothesis: Distinct dyskerin pools differ in RNA recruitment rather than simply in catalytic-domain presence.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)