9qb2

Structural highlights

Disease

DKC1_HUMAN Dyskeratosis congenita;Hoyeraal-Hreidarsson syndrome. The disease is caused by variants affecting the gene represented in this entry. Reduced rRNA pseudouridine levels in cells from patients (PubMed:25219674).^[1] The disease is caused by variants affecting the gene represented in this entry. The disease may be caused by variants affecting the gene represented in this entry.

Function

DKC1_HUMAN Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:25219674, PubMed:32554502). This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1 (PubMed:25219674). Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance (PubMed:19179534, PubMed:25219674). Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (PubMed:19179534).^{[2] [3] [4]} Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression.^[5]

References

1. ↑ Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH, León-Ricardo BX, Engreitz JM, Guttman M, Satija R, Lander ES, Fink G, Regev A. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell. 2014 Sep 25;159(1):148-162. PMID:25219674 doi:10.1016/j.cell.2014.08.028
2. ↑ Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE. A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science. 2009 Jan 30;323(5914):644-8. PMID:19179534 doi:10.1126/science.1165357
3. ↑ Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH, León-Ricardo BX, Engreitz JM, Guttman M, Satija R, Lander ES, Fink G, Regev A. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell. 2014 Sep 25;159(1):148-162. PMID:25219674 doi:10.1016/j.cell.2014.08.028
4. ↑ Balogh E, Chandler JC, Varga M, Tahoun M, Menyhárd DK, Schay G, Goncalves T, Hamar R, Légrádi R, Szekeres Á, Gribouval O, Kleta R, Stanescu H, Bockenhauer D, Kerti A, Williams H, Kinsler V, Di WL, Curtis D, Kolatsi-Joannou M, Hammid H, Szőcs A, Perczel K, Maka E, Toldi G, Sava F, Arrondel C, Kardos M, Fintha A, Hossain A, D'Arco F, Kaliakatsos M, Koeglmeier J, Mifsud W, Moosajee M, Faro A, Jávorszky E, Rudas G, Saied MH, Marzouk S, Kelen K, Götze J, Reusz G, Tulassay T, Dragon F, Mollet G, Motameny S, Thiele H, Dorval G, Nürnberg P, Perczel A, Szabó AJ, Long DA, Tomita K, Antignac C, Waters AM, Tory K. Pseudouridylation defect due to DKC1 and NOP10 mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15137-15147. PMID:32554502 doi:10.1073/pnas.2002328117
5. ↑ Angrisani A, Turano M, Paparo L, Di Mauro C, Furia M. A new human dyskerin isoform with cytoplasmic localization. Biochim Biophys Acta. 2011 Dec;1810(12):1361-8. PMID:21820037 doi:10.1016/j.bbagen.2011.07.012