Homodirectional changes in transcriptome composition and mRNA translation induced by rapamycin and heat shock

Nat Struct Biol. 2003 Dec;10(12):1039-47. doi: 10.1038/nsb1015. Epub 2003 Nov 9.

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.'

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / pharmacology
  • Hot Temperature
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Protein Biosynthesis* / drug effects
  • RNA, Fungal / drug effects
  • RNA, Fungal / genetics
  • RNA, Fungal / isolation & purification
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics*
  • RNA, Messenger / isolation & purification
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / antagonists & inhibitors
  • Sirolimus / pharmacology*
  • Thermodynamics
  • Transcription, Genetic* / drug effects

Substances

  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Fungal
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR1 protein, S cerevisiae
  • Sirolimus