biostudies-literatureBellodi CIntramural NIH HHSNIDDK NIH HHSHoward Hughes Medical InstituteNHLBI NIH HHSNIGMS NIH HHS1493-502https://www.ebi.ac.uk/biostudies/studies/S-EPMC3857015biostudies-literatureUnknown3(5)Noncoding RNAs control critical cellular processes, although their contribution to disease remains largely unexplored. Dyskerin associates with hundreds of H/ACA small RNAs to generate a multitude of functionally distinct ribonucleoproteins (RNPs). The DKC1 gene, encoding dyskerin, is mutated in the multisystem disorder X-linked dyskeratosis congenita (X-DC). A central question is whether DKC1 mutations affect the stability of H/ACA RNPs, including those modifying ribosomal RNA (rRNA). We carried out comprehensive profiling of dyskerin-associated H/ACA RNPs, revealing remarkable heterogeneity in the expression and function of subsets of H/ACA small RNAs in X-DC patient cells. Using a mass spectrometry approach, we uncovered single-nucleotide perturbations in dyskerin-guided rRNA modificatiCell reportsH/ACA small RNA dysfunctions in disease reveal key roles for noncoding RNA modifications in hematopoietic stem cell differentiation.PMC38570158P41GM103481P41 GM103481R01DK098057R01 DK0980573R01HL085572-05S1R01 HL085572R01HL085572Shimamura AMaltby DBellodi CContreras ASavage SAMcMahon MJuliano DKopmar NNakamura TRuggero DBurlingame AfalseH/ACA small RNA dysfunctions in disease reveal key roles for noncoding RNA modifications in hematopoietic stem cell differentiation.Noncoding RNAs control critical cellular processes, although their contribution to disease remains largely unexplored. Dyskerin associates with hundreds of H/ACA small RNAs to generate a multitude of functionally distinct ribonucleoproteins (RNPs). The DKC1 gene, encoding dyskerin, is mutated in the multisystem disorder X-linked dyskeratosis congenita (X-DC). A central question is whether DKC1 mutations affect the stability of H/ACA RNPs, including those modifying ribosomal RNA (rRNA). We carried out comprehensive profiling of dyskerin-associated H/ACA RNPs, revealing remarkable heterogeneity in the expression and function of subsets of H/ACA small RNAs in X-DC patient cells. Using a mass spectrometry approach, we uncovered single-nucleotide perturbations in dyskerin-guided rRNA modificati2013-01-01T00:00:00Z2013 May2026-04-29T01:03:17.561Z2019-03-27T01:18:14ZS-EPMC38570152370706210.1016/j.celrep.2013.04.030