Loss of a Conserved tRNA Anticodon Modification Perturbs Cellular Signaling

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Transfer RNA (tRNA) modifications enhance the efficiency, specificity and fidelity of translation in all organisms. The anticodon modification mcm⁵s²U³⁴ is required for normal growth and stress resistance in yeast; mutants lacking this modification have numerous phenotypes. Mutations in the homologous human genes are linked to neurological disease. The yeast phenotypes can be ameliorated by overexpression of specific tRNAs, suggesting that the modifications are necessary for efficient translation of specific codons. We determined the in vivo ribosome distributions at single codon resolution in yeast strains lacking mcm⁵s²U. We found accumulations at AAA, CAA, and GAA codons, suggesting that translation is slow when these codons are in the ribosomal A site, but these changes appeared too small to affect protein output. Instead, we observed activation of the GCN4-mediated stress response by a non-canonical pathway. Thus, loss of mcm⁵s²U causes global effects on gene expression due to perturbation of cellular signaling.

Vyšlo v časopise: Loss of a Conserved tRNA Anticodon Modification Perturbs Cellular Signaling. PLoS Genet 9(8): e32767. doi:10.1371/journal.pgen.1003675
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003675

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