Homodirectional changes in transcriptome composition and mRNA translation induced by rapamycin and heat shock.
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.'
Preiss
Thomas
T
EMBL Heidelberg, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Baron-Benhamou
Julie
J
Ansorge
Wilhelm
W
Hentze
Matthias W
MW
D004791:Enzyme Inhibitors / Q000494:pharmacology; D006358:Hot Temperature; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects; D012331:RNA, Fungal / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000494:pharmacology*; D013816:Thermodynamics; D014158:Transcription, Genetic / Q000187:drug effects
D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; C083324:TOR1 protein, S cerevisiae