rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells
(2011) In Molecular Cell 44(4). p.6-660- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2011-11-18
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 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
- in
- Molecular Cell
- volume
- 44
- issue
- 4
- pages
- 7 pages
- publisher
- Cell Press
- external identifiers
-
- scopus:81355153985
- pmid:22099312
- ISSN
- 1097-4164
- DOI
- 10.1016/j.molcel.2011.09.017
- language
- English
- LU publication?
- no
- id
- 21155f13-a460-4755-bb6d-7925968b8683
- date added to LUP
- 2016-04-29 15:46:30
- date last changed
- 2024-09-07 10:54:58
@article{21155f13-a460-4755-bb6d-7925968b8683, abstract = {{<p>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.</p>}}, author = {{Jack, Karen and Bellodi, Cristian and Landry, Dori M and Niederer, Rachel O and Meskauskas, Arturas and Musalgaonkar, Sharmishtha and Kopmar, Noam and Krasnykh, Olya and Dean, Alison M and Thompson, Sunnie R and Ruggero, Davide and Dinman, Jonathan D}}, issn = {{1097-4164}}, keywords = {{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}}, language = {{eng}}, month = {{11}}, number = {{4}}, pages = {{6--660}}, publisher = {{Cell Press}}, series = {{Molecular Cell}}, title = {{rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells}}, url = {{http://dx.doi.org/10.1016/j.molcel.2011.09.017}}, doi = {{10.1016/j.molcel.2011.09.017}}, volume = {{44}}, year = {{2011}}, }