dyskerin

Dyskerin is a highly conserved nucleolar protein encoded by the DKC1 gene in humans. It serves as the catalytic subunit of the H/ACA small nucleolar ribonucleoprotein particles (snoRNPs) that guide the pseudouridylation of ribosomal RNA. Through its enzymatic activity and association with RNA guides, dyskerin contributes to proper rRNA processing and ribosome biogenesis.

In the H/ACA snoRNP complex, dyskerin partners with accessory proteins to modify uridine residues to pseudouridine in rRNA, a modification important for ribosome structure and function. The protein also participates in the maturation and stable accumulation of the RNA components that guide these snoRNPs, linking its activity to broader RNA processing pathways. Beyond ribosomal RNA, dyskerin associates with the telomerase complex, binding to the telomerase RNA component (TERC) and helping stabilize the RNA and assemble an active ribonucleoprotein enzyme that maintains telomere length.

Dyskerin is primarily localized in the nucleolus, with presence in Cajal bodies where small RNAs and RNPs are assembled. It forms a core component of the H/ACA snoRNPs with GAR1, NOP10, and NHP2, and it also interacts with the telomerase RNA component, linking its roles in RNA modification and telomere biology.

Mutations in DKC1 cause X-linked dyskeratosis congenita, a telomere biology disorder characterized by progressive bone marrow failure, mucocutaneous abnormalities, and an increased cancer risk. Some mutations yield severe phenotypes, such as Hoyeraal-Hreidarsson syndrome, reflecting combined defects in ribosome biogenesis and telomere maintenance.