Decoupling of transcript and protein concentrations ensures budding yeast histone homeostasis in different nutrient conditions

Abstract

To maintain protein homeostasis in changing nutrient environments, cells must precisely control the amount of their proteins, despite the accompanying changes in cell growth and biosynthetic capacity. As nutrients are major regulators of cell cycle length and progression, a particular challenge arises for the nutrient-dependent regulation of cell cycle genes, which are periodically expressed during the cell cycle. One important example are histones, which are needed at a constant histone-to-DNA stoichiometry. Here we show that budding yeast achieves histone homeostasis in different nutrients through a decoupling of transcript and protein abundance. We find that cells downregulate histone transcripts in poor nutrients to avoid toxic histone overexpression, but produce constant amounts of histone proteins through nutrient-specific regulation of translation efficiency. Our findings suggest that this allows cells to balance the need for rapid histone production under fast growth conditions with the tight regulation required to avoid toxic overexpression in poor nutrients.

An mTOR/RNA pol I axis shapes chromatin architecture in response to fasting

“…Intestinal nuclei were manually segmented in 2D using Cell-ACDC (49) based on HIS-72-GFP or Hoechst 33342 signal and stacked into 3D "cylindrical" objects. To detect and quantify the volume of nucleoli in 3D, we adapted the spot detection routine developed in (50) and (51). The analysis steps are the following: 1) Application of a 3D gaussian filter with a small sigma (0.75 voxel) of the FIB-1::mCherry signal.…”