Abstract
Transcription and mRNA turnover determine the quantitative composition of the cellular transcriptome. The transcriptome in turn serves as a template for the proteome via translation. Treatment of Saccharomyces cerevisiae with the TOR kinase inhibitor rapamycin causes increases and decreases in the mRNA levels of hundreds of genes. We used DNA microarray analysis to monitor simultaneously transcriptome and translational changes for all detectable yeast mRNAs. Notably, genes that are induced in the transcriptome correlate tightly with more efficiently translated mRNAs (based on their relative degree of polyribosome association); similarly, genes that show reduced mRNA levels after rapamycin treatment also show lower translational fitness. Microarray analyses on heat-shocked cells also reveal homodirectional co-regulatory responses. Thus, signal-induced changes in the transcriptome are amplified at the translational level. These results unveil a higher level of coordinated gene regulation that we refer to as 'potentiation.'
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Acknowledgements
We thank all members of the EMBL microarray community, past and present, for fruitful interactions throughout this work, and for their contributions to the establishment of microarray technology at EMBL. We also thank M. Altmann, J.E.G. McCarthy, A.B. Sachs, B. Seraphin, G. Kornfeld, T. Lithgow, M. Knop and M. Seedorf for the gift of strains and reagents. This work was funded by grants from the Deutsche Forschungsgemeinschaft to T.P. and M.W.H. and from the Human Frontiers in Science Program to M.W.H.
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41594_2003_BFnsb1015_MOESM1_ESM.pdf
Supplementary Fig. 1. Correlation of mRNA translation state with length of the open reading frame (ORF). Translation state ratios from the control cell measurement in array set I were plotted against ORF size and a Lowess curve was fitted to all data points (solid line). The mRNA frequency in a given length interval (size: 200 amino acids) is shown for comparison (dashed line). The correlation breaks down beyond 2500 amino acids as there is only a statistically insignificant number of scored genes (n=12 in total) in this size region. (PDF 16 kb)
41594_2003_BFnsb1015_MOESM2_ESM.pdf
Supplementary Fig. 2. Selection of mRNA profiles. a, mRNAs were selected for translational state ratio change in response to rapamycin from array data set I as detailed in the main text and Fig. 3A-C. b, mRNAs were selected based on their polysome re-distribution profile from array data set II. Profiles were sorted into a 9x8 matrix using a self-organising map algorithm (GeneSpring 5.0) and then assigned to different candidate groups for translational behaviour as indicated by the coloured frames. (PDF 188 kb)
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Preiss, T., Baron-Benhamou, J., Ansorge, W. et al. Homodirectional changes in transcriptome composition and mRNA translation induced by rapamycin and heat shock. Nat Struct Mol Biol 10, 1039–1047 (2003). https://doi.org/10.1038/nsb1015
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DOI: https://doi.org/10.1038/nsb1015
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