RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size

A fundamental feature of cellular growth is that total protein and RNA amounts increase with cell size to keep concentrations approximately constant. A key component to this is that global transcription rates increase in larger cells. Here, we identify RNAPII as the limiting factor scaling mRNA transcription with cell size in budding yeast, as transcription is highly sensitive to the dosage of RNAPII but not to other components of the transcriptional machinery. Our experiments support a dynamic equilibrium model where global RNAPII transcription at a given size is set by the mass-action recruitment kinetics of unengaged nucleoplasmic RNAPII to the genome. However, this only drives a sub-linear increase in transcription with size, which is then partially compensated for by a decrease in mRNA decay rates as cells enlarge. Thus, limiting RNAPII and feedback on mRNA stability work in concert to scale mRNA amounts with cell size. ChIP-seq and RNA-seq experiments using S. cerevisiae with a spike-in of S. pombe or C. glabrata cells for spike-in normalisation.