Loss of a conserved tRNA anticodon modification perturbs cellular signaling

Transfer RNA (tRNA) modifications enhance the efficiency, specificity and fidelity of translation in all organisms. The anticodon modification mcm(5)s(2)U(34) is required for normal growth and stress resistance in yeast; mutants lacking this modification have numerous phenotypes. Mutations in the ho...

Full description

Saved in:
Bibliographic Details
Published in:PLoS genetics 2013-08, Vol.9 (8), p.e1003675-e1003675
Main Authors: Zinshteyn, Boris, Gilbert, Wendy V
Format: Article
Language:English
Subjects:
Anticodon - genetics
Biology
Cellular signal transduction
Codon
Codon - genetics
Defects
Efficiency
Gene expression
Genomes
Humans
Microbiology
Mutation
Nucleic Acid Conformation
Physiological aspects
Plasmids
Protein Biosynthesis
Proteins
Ribosomes - genetics
RNA sequencing
RNA, Transfer - genetics
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Signal Transduction - genetics
Stress response
Transfer RNA
Yeast
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Transfer RNA (tRNA) modifications enhance the efficiency, specificity and fidelity of translation in all organisms. The anticodon modification mcm(5)s(2)U(34) 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 mcm(5)s(2)U. 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 mcm(5)s(2)U causes global effects on gene expression due to perturbation of cellular signaling.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1003675