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Series GSE67387 Query DataSets for GSE67387
Status Public on Jun 04, 2015
Title Optimization of codon translation rates via tRNA modifications maintains proteome integrity
Organisms Saccharomyces cerevisiae; Caenorhabditis elegans
Experiment type Expression profiling by high throughput sequencing
Summary Proteins begin to fold as they emerge from translating ribosomes. The kinetics of ribosome transit along a given mRNA can influence nascent chain folding, but the extent to which individual codon translation rates impact proteome integrity remains unknown. Here, we show that slower decoding of discrete codons elicits widespread protein aggregation in vivo. Using ribosome profiling, we find that loss of anticodon wobble uridine (U34) modifications in a subset of tRNAs leads to ribosome pausing at their cognate codons in S. cerevisiae and C. elegans. Yeast cells lacking U34 modifications exhibit gene expression hallmarks of proteotoxic stress and accumulate aggregates of endogenous proteins with key cellular functions. Moreover, these cells are severely compromised in clearing stress-induced protein aggregates. Overexpression of hypomodified tRNAs alleviates ribosome pausing, concomitantly restoring protein homeostasis. Our findings demonstrate that modified U34 is an evolutionarily conserved accelerator of decoding and reveal an unanticipated role for tRNA anticodon modifications in maintaining proteome integrity.
 
Overall design Ribosome profiling of wild-type and tRNA modification-deficient yeast and nematodes. Yeast samples were generated in various growth conditions (rich medium versus stress induced by treatment with diamide or rapamycin) and paired mRNA-Seq was performed on a subset of samples. Dataset contains three biological replicates for yeast samples and two biological replicates for nematode samples.
 
Contributor(s) Nedialkova DD, Leidel SA
Citation(s) 26052047
Submission date Mar 28, 2015
Last update date May 15, 2019
Contact name Danny D. Nedialkova
E-mail(s) danny.nedialkova@mpi-muenster.mpg.de
Organization name Max Planck Institute for Molecular Biomedicine
Department Max Planck Research Group for RNA Biology
Street address Von-Esmarch-Str. 54
City Münster
ZIP/Postal code 48149
Country Germany
 
Platforms (2)
GPL19958 Illumina HiScanSQ (Saccharomyces cerevisiae)
GPL19959 Illumina HiScanSQ (Caenorhabditis elegans)
Samples (98)
GSM1646015 WT_ribo_YPD_rep1
GSM1646016 WT_ribo_YPD_rep2
GSM1646017 WT_ribo_YPD_rep3
Relations
BioProject PRJNA279785
SRA SRP056647

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE67387_Celeg_mRNA_rawCounts.txt.gz 177.8 Kb (ftp)(http) TXT
GSE67387_Celeg_ribo_rawCounts.txt.gz 134.3 Kb (ftp)(http) TXT
GSE67387_Scer_mRNA_rawCounts.txt.gz 277.0 Kb (ftp)(http) TXT
GSE67387_Scer_ribo_rawCounts.txt.gz 336.3 Kb (ftp)(http) TXT
GSE67387_Scer_ribo_tKQE_rawCounts.txt.gz 159.0 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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