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rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells.

Molecular cell | Nov 18, 2011

http://www.ncbi.nlm.nih.gov/pubmed/22099312

How pseudouridylation (Ψ), the most common and evolutionarily conserved modification of rRNA, regulates ribosome activity is poorly understood. Medically, Ψ is important because the rRNA Ψ synthase, DKC1, is mutated in X-linked dyskeratosis congenita (X-DC) and Hoyeraal-Hreidarsson (HH) syndrome. Here, we characterize ribosomes isolated from a yeast strain in which Cbf5p, the yeast homolog of DKC1, is catalytically impaired through a D95A mutation (cbf5-D95A). Ribosomes from cbf5-D95A cells display decreased affinities for tRNA binding to the A and P sites as well as the cricket paralysis virus internal ribosome entry site (IRES), which interacts with both the P and the E sites of the ribosome. This biochemical impairment in ribosome activity manifests as decreased translational fidelity and IRES-dependent translational initiation, which are also evident in mouse and human cells deficient for DKC1 activity. These findings uncover specific roles for Ψ modification in ribosome-ligand interactions that are conserved in yeast, mouse, and humans.

Pubmed ID: 22099312 RIS Download

Mesh terms: Animals | Binding Sites | Cell Cycle Proteins | Dyskeratosis Congenita | Fetal Growth Retardation | Genes, Reporter | Humans | Hydro-Lyases | Intellectual Disability | Luciferases | Mice | Microcephaly | Microtubule-Associated Proteins | Mutation | Nuclear Proteins | Plasmids | Protein Biosynthesis | RNA, Ribosomal | RNA, Transfer | Ribonucleoproteins, Small Nuclear | Ribosomes | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Sequence Homology, Amino Acid | Transduction, Genetic

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Associated grants

  • Agency: NIGMS NIH HHS, Id: 3R01GM058859-10A1S1
  • Agency: NIGMS NIH HHS, Id: 3R01GM084547-01A1S1
  • Agency: NHLBI NIH HHS, Id: 3R01HL085572-05S1
  • Agency: NIGMS NIH HHS, Id: 5R01GM058859
  • Agency: NIGMS NIH HHS, Id: R01 GM058859
  • Agency: NIGMS NIH HHS, Id: R01 GM058859-10A1
  • Agency: NIGMS NIH HHS, Id: R01 GM058859-10A1S1
  • Agency: NIGMS NIH HHS, Id: R01 GM058859-11
  • Agency: NIGMS NIH HHS, Id: R01 GM058859-12
  • Agency: NIGMS NIH HHS, Id: R01 GM058859-13
  • Agency: NIGMS NIH HHS, Id: R01 GM084547
  • Agency: NIGMS NIH HHS, Id: R01 GM084547-01A1S1
  • Agency: NIGMS NIH HHS, Id: R01 GM084547-02
  • Agency: NIGMS NIH HHS, Id: R01 GM084547-03
  • Agency: NIGMS NIH HHS, Id: R01 GM084547-04
  • Agency: NHLBI NIH HHS, Id: R01 HL085572
  • Agency: NHLBI NIH HHS, Id: R01 HL085572-03
  • Agency: NHLBI NIH HHS, Id: R01 HL085572-04
  • Agency: NHLBI NIH HHS, Id: R01 HL085572-05
  • Agency: NHLBI NIH HHS, Id: R01 HL085572-05S1
  • Agency: NIGMS NIH HHS, Id: R01GM084547
  • Agency: NHLBI NIH HHS, Id: R01HL085572

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