Gene transcription as a limiting factor in protein production and cell growth

Abstract

AbstractGrowth rate and cell size are principle characteristics of proliferating cells, whose values depend on cellular biosynthetic processes in a way poorly understood. Protein production is critical for growth, and we therefore examined for processes limiting this production. Burdening cells with an excess of inert protein changed endogenous gene expression similarly to transcription-perturbing mutants, was epistatic to these mutants, but did not deplete respective factors from gene promoters. Mathematical modeling, corroborated by experiments, attributed this signature to a feedback which proportionally increases all endogenous gene expression, but lags at fast initiating genes already transcribed close to the maximal possible rate. As a possible benefit of maximizing transcription rates, we discuss a conflict between cell growth rate and size, which emerges above a critical cell size set by transcript abundance. We propose that biochemical limits on protein and mRNA production define the characteristic values of cell size and division time.