RNA polymerase II dynamics and mRNA stability feedback determine mRNA scaling with cell size

Abstract

A fundamental feature of cellular growth is that protein and RNA amounts scale with cell size so that concentrations remain constant. A key component to this is that global transcription rates increase in larger cells, but the underlying mechanism has remained unknown. Here, we identify RNAPII as the major limiting factor increasing transcription with cell size in budding yeast as transcription is highly sensitive to the dosage of RNAPII but not to other components of the general transcriptional machinery. Our experiments support a dynamic equilibrium model where global transcription at a given size is set by the mass-action recruitment kinetics of unengaged nucleoplasmic RNAPII, and DNA content. This drives a sub-linear increase in transcription with size, which is precisely compensated for by a decrease in mRNA decay rates as cells enlarge. Thus, limiting RNAPII and feedback on mRNA stability work in concert to ensure mRNA concentration homeostasis in growing cells.