Journal
NUCLEIC ACIDS RESEARCH
Volume 37, Issue 22, Pages 7665-7677Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkp816
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Funding
- Agence Nationale pour la Recherche [ANR-06-BLAN-0391-01]
- Association pour la Recherche sur le Cancer [3849]
- Association Francaise contre les Myopathies [12652]
- US National Institutes of Health [Gm19351]
- Agence Nationale de la Recherche (ANR) [ANR-06-BLAN-0391] Funding Source: Agence Nationale de la Recherche (ANR)
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Important regions of rRNA are rich in nucleotide modifications that can have strong effects on ribosome biogenesis and translation efficiency. Here, we examine the influence of pseudouridylation and 2'-O-methylation on translation accuracy in yeast, by deleting the corresponding guide snoRNAs. The regions analyzed were: the decoding centre (eight modifications), and two intersubunit bridge domains-the A-site finger and Helix 69 (six and five modifications). Results show that a number of modifications influence accuracy with effects ranging from 0.3- to 2.4-fold of wild-type activity. Blocking subsets of modifications, especially from the decoding region, impairs stop codon termination and reading frame maintenance. Unexpectedly, several Helix 69 mutants possess ribosomes with increased fidelity. Consistent with strong positional and synergistic effects is the finding that single deletions can have a more pronounced phenotype than multiple deficiencies in the same region. Altogether, the results demonstrate that rRNA modifications have significant roles in translation accuracy.
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