title: Anomalous electrophoretic migration of newly synthesized ribosomal RNAs and their precursors from cells with DKC1 mutations.
abstract: Mutations in the X-linked gene, DKC1, encoding dyskerin, cause dyskeratosis congenita by leading to decreased telomerase activity and causing short telomeres. Dyskerin is also a pseudouridine synthase that modifies nascent ribosomal and other RNAs and it is not known if this function is affected by the mutations. Here we show that newly synthesized ribosomal RNA, extracted from human and mouse cells with pathogenic mutations, shows anomalous mobility in agarose gels under certain denaturation conditions. The anomalously migrating RNA is turned over rapidly. Analysis of ribosomal RNA in these cells suggests the altered mobility is due to inefficient pseudouridylation.
authors.affiliation: Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Bai-Wei
authors.initials: BW
authors.lastname: Gu
authors.forename: Chunjun
authors.initials: C
authors.lastname: Zhao
authors.forename: Jian-Meng
authors.initials: JM
authors.lastname: Fan
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.forename: Monica
authors.initials: M
authors.lastname: Bessler
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mason
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D004586:Electrophoresis; D006801:Humans; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011560:Pseudouridine / Q000378:metabolism; D020871:RNA Stability; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000737:chemistry*
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; C510431:Dkc1 protein, mouse; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D011560:Pseudouridine