Dyskerin Explained

H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the gene DKC1.^{[1] [2] [3]}

Dyskerin is a pseudouridine synthase enzyme which is part of the TruB family of enzymes.^[4] Dyskerin is an L-shaped protein of 514 residues and a molecular weight of about 58 kilo-daltons. Dyskerin is essential for the activity of telomerase by accumulating telomerase RNA component (TERC).

This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the NOLA1, 2 and 3 proteins. The protein encoded by this gene and the three NOLA proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The protein encoded by this gene is related to the Saccharomyces cerevisiae Cbf5p and Drosophila melanogaster Nop60B proteins. The gene lies in a tail-to-tail orientation with the palmitoylated erythrocyte membrane protein (MPP1) gene and is transcribed in a telomere to centromere direction. Both nucleotide substitutions and single trinucleotide repeat polymorphisms have been found in this gene. Mutations in this gene cause X-linked dyskeratosis congenita.^[3]

Clinical significance

Mutations in DKC1 are associated to Hoyeraal-Hreidarsson syndrome.^[5]

Further reading

• Marrone A, Dokal I . Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer . Expert Reviews in Molecular Medicine . 6 . 26 . 1–23 . 2004 . 15613268 . 10.1017/S1462399404008671 . 38163343 .
• Yamaguchi H . Mutations of telomerase complex genes linked to bone marrow failures . Journal of Nippon Medical School . 74 . 3 . 202–9 . 2007 . 17625368 . 10.1272/jnms.74.202. free .
• Aalfs CM, van den Berg H, Barth PG, Hennekam RC . The Hoyeraal-Hreidarsson syndrome: the fourth case of a separate entity with prenatal growth retardation, progressive pancytopenia and cerebellar hypoplasia . Eur. J. Pediatr. . 154 . 4 . 304–8 . 1995 . 7607282 . 10.1007/BF01957367 . 441225 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Devriendt K, Matthijs G, Legius E . Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita . Am. J. Hum. Genet. . 60 . 3 . 581–7 . 1997 . 9042917 . 1712491 . etal.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
• McGrath JA . Dyskeratosis congenita: new clinical and molecular insights into ribosome function . Lancet . 353 . 9160 . 1204–5 . 1999 . 10217077 . 10.1016/S0140-6736(99)00011-2 . 490860 .
• Knight SW, Heiss NS, Vulliamy TJ . X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene . Am. J. Hum. Genet. . 65 . 1 . 50–8 . 1999 . 10364516 . 10.1086/302446 . 1378074 . etal.
• Vulliamy TJ, Knight SW, Heiss NS . Dyskeratosis congenita caused by a 3' deletion: germline and somatic mosaicism in a female carrier . Blood . 94 . 4 . 1254–60 . 1999 . 10.1182/blood.V94.4.1254 . 10438713 . etal.
• Heiss NS, Girod A, Salowsky R . Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita . Hum. Mol. Genet. . 8 . 13 . 2515–24 . 2000 . 10556300 . 10.1093/hmg/8.13.2515 . etal.
• Knight SW, Heiss NS, Vulliamy TJ . Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1 . Br. J. Haematol. . 107 . 2 . 335–9 . 2000 . 10583221 . 10.1046/j.1365-2141.1999.01690.x . 23750791 . etal.
• Mitchell JR, Wood E, Collins K . A telomerase component is defective in the human disease dyskeratosis congenita . Nature . 402 . 6761 . 551–5 . 1999 . 10591218 . 10.1038/990141 . 1999Natur.402..551M . 4430482 .
• Yaghmai R, Kimyai-Asadi A, Rostamiani K . Overlap of dyskeratosis congenita with the Hoyeraal-Hreidarsson syndrome . J. Pediatr. . 136 . 3 . 390–3 . 2000 . 10700698 . 10.1067/mpd.2000.104295 . etal. free .
• Heiss NS, Bächner D, Salowsky R . Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1 . Genomics . 67 . 2 . 153–63 . 2000 . 10903840 . 10.1006/geno.2000.6227 . etal.
• Pogacić V, Dragon F, Filipowicz W . Human H/ACA Small Nucleolar RNPs and Telomerase Share Evolutionarily Conserved Proteins NHP2 and NOP10 . Mol. Cell. Biol. . 20 . 23 . 9028–40 . 2000 . 11074001 . 10.1128/MCB.20.23.9028-9040.2000 . 86556 .
• Hartley JL, Temple GF, Brasch MA . DNA Cloning Using In Vitro Site-Specific Recombination . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Simpson JC, Wellenreuther R, Poustka A . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Rep. . 1 . 3 . 287–92 . 2001 . 11256614 . 10.1093/embo-reports/kvd058 . 1083732 . etal.
• Knight SW, Vulliamy TJ, Morgan B . Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis . Hum. Genet. . 108 . 4 . 299–303 . 2001 . 11379875 . 10.1007/s004390100494 . 23829134 . etal.

External links

• GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita

Notes and References

1. Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A, Dokal I . X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions . Nat Genet . 19 . 1 . 32–8 . May 1998 . 9590285 . 10.1038/ng0598-32 . 205342127 .
2. Hassock S, Vetrie D, Giannelli F . Mapping and characterization of the X-linked dyskeratosis congenita (DKC) gene . Genomics . 55 . 1 . 21–7 . Mar 1999 . 9888995 . 10.1006/geno.1998.5600 .
3. Web site: Entrez Gene: DKC1 dyskeratosis congenita 1, dyskerin.
4. Garus A, Autexier C . Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance . . 27 . 12 . 1441–1458 . 2021 . 10.1261/rna.078953.121 . 8594475 . 34556550.
5. 24914498. 2014. Lim. B. C.. Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole-exome sequencing. Gene. Yoo. S. K.. Lee. S. Shin. J. Y.. Hwang. H. Chae. J. H.. Hwang. Y. S.. Seo. J. S.. Kim. J. I.. Kim. K. J.. 10.1016/j.gene.2014.06.011 . 546 . 2 . 425–9.