Anomalous electrophoretic migration of newly synthesized ribosomal RNAs and their precursors from cells with DKC1 mutations.
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.
Gu
Bai-Wei
BW
Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Zhao
Chunjun
C
Fan
Jian-Meng
JM
Dai
Qing
Q
Bessler
Monica
M
Mason
Philip J
PJ
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*
D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; C510431:Dkc1 protein, mouse; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D011560:Pseudouridine