Dyskerin

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"DKC1" redirects here. For the 1994 video game, see Donkey Kong Country.

DKC1
Identifiers
AliasesDKC1, CBF5, DKC, DKCX, NAP57, NOLA4, XAP101, Dyskerin, dyskerin pseudouridine synthase 1
External IDsOMIM: 300126; MGI: 1861727; HomoloGene: 1045; GeneCards: DKC1; OMA:DKC1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1736

245474

Ensembl

ENSG00000130826

ENSMUSG00000031403

UniProt

O60832

Q9ESX5

RefSeq (mRNA)

NM_001142463
NM_001288747
NM_001363

NM_001030307
NM_001359411
NM_001359412
NM_001359413

RefSeq (protein)

NP_001135935
NP_001275676
NP_001354

NP_001025478
NP_001346340
NP_001346341
NP_001346342

Location (UCSC)Chr X: 154.76 – 154.78 MbChr X: 74.14 – 74.15 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the DKC1 gene.[5][6][7] The encoded protein, known as dyskerin, is a highly conserved nucleolar enzyme that plays key roles in rRNA modification, telomerase function, and ribosome biogenesis.

Structure

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Dyskerin is an L-shaped protein consisting of approximately 514 amino acid residues, with a molecular weight of about 58 kilo-daltons.[8] It belongs to the TruB family of pseudouridine synthase enzymes and forms the catalytic core of the H/ACA box snoRNP (small nucleolar ribonucleoprotein) complex. The DKC1 gene is located on the X chromosome, in a tail-to-tail orientation with the gene encoding palmitoylated erythrocyte membrane protein 1 (MPP1), and is transcribed in a telomere-to-centromere direction.[7]

Function

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The DKC1 gene encodes a core component of the H/ACA snoRNP complex, which also includes the NOLA1, NOLA2, and NOLA3 proteins. These proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. The H/ACA snoRNPs catalyze pseudouridylation of rRNA and are essential for proper ribosome biogenesis. Depletion of any of the four core proteins impairs 18S rRNA production and pseudouridylation.[7]

Beyond rRNA modification, dyskerin contributes to several other fundamental processes. It stabilizes the telomerase RNA component (TERC), thereby maintaining telomerase activity and ensuring telomere elongation and genomic stability.[8] Dyskerin also participates in the assembly and maturation of ribosomal subunits by promoting correct folding and processing of pre-rRNA intermediates. In addition, it has been implicated in the regulation of pre-mRNA splicing, potentially through interactions with small Cajal body-specific RNAs (scaRNAs) that guide pseudouridylation of spliceosomal RNAs.[8]

The human protein is homologous to Saccharomyces cerevisiae Cbf5p and Drosophila melanogaster Nop60B proteins, indicating strong evolutionary conservation.[7]

Clinical significance

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Mutations in DKC1 cause X-linked dyskeratosis congenita, a rare inherited disorder characterized by defective telomere maintenance, premature aging, bone marrow failure, and increased cancer susceptibility.[5][6][7] Both nucleotide substitutions and trinucleotide repeat polymorphisms have been identified in this gene. The pathogenic variants typically impair dyskerin function, disrupting rRNA modification and telomerase RNA stability, leading to the disease phenotype.

Mutations in DKC1 are also associated with Hoyeraal-Hreidarsson syndrome.[9]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000130826 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031403 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, et al. (May 1998). "X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions". Nature Genetics. 19 (1): 32–38. doi:10.1038/ng0598-32. PMID 9590285. S2CID 205342127.
  6. ^ a b Hassock S, Vetrie D, Giannelli F (January 1999). "Mapping and characterization of the X-linked dyskeratosis congenita (DKC) gene". Genomics. 55 (1): 21–27. doi:10.1006/geno.1998.5600. PMID 9888995.
  7. ^ a b c d e "Entrez Gene: DKC1 dyskeratosis congenita 1, dyskerin".
  8. ^ a b c Garus A, Autexier C (December 2021). "Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance". RNA. 27 (12): 1441–1458. doi:10.1261/rna.078953.121. PMC 8594475. PMID 34556550.
  9. ^ Lim BC, Yoo SK, Lee S, Shin JY, Hwang H, Chae JH, et al. (August 2014). "Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole-exome sequencing". Gene. 546 (2): 425–429. doi:10.1016/j.gene.2014.06.011. PMID 24914498.

Further reading

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