DKC1 Gene

The DKC1 gene (DKC1 stands for "Dyskerin Pseudouridine Synthase 1") is a protein coding gene located on chromosome Xq28. Alternative splicing leads to several transcript variants.

The DKC1 gene functions in two different complexes. It plays an active role in the stabilization and maintenance of telomerase(see also under telomeropathy) and in the recognition of snoRNAs containing H/ACA sequences, which ensures stability during biogenesis and assembly into H/ACA ribonucleoproteins of small nucleolar RNA (snoRNPs) (see also under telomeropathies). The DKC1 gene is highly conserved. It may play additional roles in nucleo-cytoplasmic shuttling, DNA damage response, and cell adhesion.

Diseases associated with DKC1 include.

• dyskeratosis congenita, X-linked

and

• Hoyeraal-Hreidarsson syndrome (considered a severe variant of dyskeratosis congenita. Characteristic symptoms are: intrauterine growth retardation, microcephaly, cerebellar hypoplasia, progressive combined immunodeficiency and aplastic anemia).

Isoform 1: Catalytic subunit of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex that catalyzes pseudouridylation of rRNA (PubMed:25219674). This involves isomerization of uridine so that ribose is subsequently bound to C5 instead of the normal N1 (Schwartz S et al. 2014). Each rRNA may contain up to 100 pseudouridine residues ("psi"), which may serve to stabilize the conformation of rRNAs.

This complex is required for ribosome biogenesis and telomere maintenance. Also required for proper processing or intranuclear transport of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (Venteicher AS et al. 2009).

Isoform 3: Promotes cell-to-cell and cell-to-substrate adhesion, increases cell proliferation rate, and leads to hyper-expression of cytokeratin.

1. Schwartz S et al. (2014) Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159:148-162.
2. Venteicher AS et al (2009) A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science 323:644-648.
3. Wang C et al (2004) Architecture and assembly of mammalian H/ACA small nucleolar and telomerase ribonucleoproteins. EMBO J 23:1857-1867.