Growth Rate-Dependent Global Amplification of Gene Expression

Regulation of cell growth rate is essential for maintaining cellular homeostasis and survival in diverse conditions. Changes in cell growth rate result in changes in rRNA and tRNA content, but the effect of cell growth rate on mRNA abundance is not known. We developed a new method for measuring absolute transcript abundances using RNA-seq, SP ike in-based A bsolute R NA Q uantification (SPARQ), that does not assume a constant transcriptome size and applied it to the model eukaryote, Saccharomyces cerevisiae (budding yeast), grown at different rates. We find that increases in cell growth rate result in increased absolute abundance of almost every transcript, with significant coordinated changes in abundances among functionally related transcripts. mRNA degradation and synthesis rates increase with increased growth rate, but to differing extents, resulting in the observed net increases in absolute abundance. We propose that regulation of ribosome abundance links environmental conditions to transcriptome amplification via nutrient-sensing pathways.