Abstract
Dyskerin is a protein involved in the formation of small nucleolar and small Cajal body ribonucleoproteins. These complexes participate in RNA pseudouridylation and are also components of the telomerase complex required for telomere elongation. Dyskerin mutations cause a rare disease, X-linked dyskeratosis congenita, with no curative treatment. The social amoeba Dictyostelium discoideum contains a gene coding for a dyskerin homologous protein. In this article D. discoideum mutant strains that have mutations corresponding to mutations found in dyskeratosis congenita patients are described. The phenotype of the mutant strains has been studied and no alterations were observed in pseudouridylation activity and telomere structure. Mutant strains showed increased proliferation on liquid culture but reduced growth feeding on bacteria. The results obtained indicated the existence of increased DNA damage response and reactive oxygen species, as also reported in human Dyskeratosis congenita cells and some other disease models. These data, together with the haploid character of D. discoideum vegetative cells, that resemble the genomic structure of the human dyskerin gene, located in the X chromosome, support the conclusion that D. discoideum can be a good model system for the study of this disease.
Highlights
Dyskerin is a nuclear protein highly conserved in archaea and eukaryotes
The functional domains identified in human dyskerin are schematically shown in Figure 1A, including the N-terminal extension (NTE), dyskerin-like domain (DKCLD), the catalytic TruB_N and the RNA-binding PUA domains
The D. discoideum protein fused to the Green Fluorescence Protein (GFP) localizes to nuclear bodies similar to nucleoli (Figure 1C)
Summary
Dyskerin is a nuclear protein highly conserved in archaea and eukaryotes. Dyskerin associates with H/ACA small nucleolar RNAs (snoRNAs) and with small Cajal Body RNAs (scaRNAs) to form ribonucleoprotein complexes (snoRNPs and scaRNPs). Dyskerin always is associated in these RNP complexes with other three highly conserved proteins, NOP10, NHP2 and GAR1 [1]. Dyskerin has pseudouridine synthase activity and is responsible for the modification of uridine residues in different RNA molecules, including ribosomal. The specificity of the reaction, including the RNA molecule and the residue modified is determined by the associated snoRNA that acts as a guide [3]. Pseudouridylation is required for the proper structure and function of these RNAs. In addition, H/ACA snoRNPs direct endonucleolytic processing of rRNA [4], enforcing the role played by dyskerin in ribosome biogenesis.
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