dyskerinCbf5

Dyskerin, encoded by the DKC1 gene in humans, is a highly conserved pseudouridine synthase that serves as the catalytic component of H/ACA small nucleolar ribonucleoproteins (snoRNPs). In yeast and archaea, the functional homolog is known as Cbf5. The protein forms a core complex with NOP10, Nhp2, and GAR1 and associates with H/ACA guide RNAs to catalyze the isomerization of uridine to pseudouridine in ribosomal RNA and small nuclear RNA, contributing to RNA stability and processing.

In mammals, dyskerin also binds the telomerase RNA component (TERC), aiding in the stabilization of telomerase RNP and facilitating telomere maintenance. This dual role links dyskerin to both ribosome biogenesis and telomere biology, making it a key factor in cellular proliferation and genome integrity. The Dyskerin-Cbf5 relationship is central to the conserved mechanism of pseudouridylation across species, and the term dyskerinCbf5 is sometimes used to emphasize this functional and evolutionary relationship between the human protein and its orthologs in other organisms.

Genetically, mutations in DKC1 cause X-linked dyskeratosis congenita (DC), a inherited disorder characterized by bone marrow failure, abnormal skin and mucosal findings, and an increased cancer risk. The DC phenotype often includes telomere shortening, reflecting impaired telomerase function, multilayered ribosome biogenesis defects, and disrupted RNA maturation. Other DC-associated genes encode components of the telomerase complex or the H/ACA snoRNPs, highlighting the interconnected roles of dyskerin/Cbf5 in RNA modification and telomere biology.

Research and clinical interest in the dyskerin-Cbf5 axis continues to focus on understanding its contributions to ribosome function, telomere maintenance, and the pathogenesis of DC, with the aim of identifying therapeutic approaches that address both RNA processing and telomere biology.