The one-message-per-cell-cycle rule: A conserved minimum transcription level for essential genes

TL;DR

This study reveals a conserved minimum transcription level of one message per cell cycle for essential genes across E. coli, yeast, and humans, which is crucial for maintaining cellular robustness against stochastic noise.

Contribution

It identifies a conserved transcriptional rule that sets a lower limit on gene expression for essential genes across diverse organisms.

Findings

Minimum one message per cell cycle for essential genes is conserved across species.

Transcriptional noise is predicted by messages transcribed per cell cycle.

Robustness to noise influences the expression levels of essential genes.

Abstract

The inherent stochasticity of cellular processes leads to significant cell-to-cell variation in protein abundance. Although this noise has already been characterized and modeled, its broader implications and significance remain unclear. In this paper, we revisit the noise model and identify the number of messages transcribed per cell cycle as the critical determinant of noise. In yeast, we demonstrate that this quantity predicts the non-canonical scaling of noise with protein abundance, as well as quantitatively predicting its magnitude. We then hypothesize that growth robustness requires an upper ceiling on noise for the expression of essential genes, corresponding to a lower floor on the transcription level. We show that just such a floor exists: a minimum transcription level of one message per cell cycle is conserved between three model organisms: Escherichia coli, yeast, and human. Furthermore, all three organisms transcribe the same number of messages per gene, per cell cycle. This common transcriptional program reveals that robustness to noise plays a central role in determining the expression level of a large fraction of essential genes, and that this fundamental optimal strategy is conserved from E. coli to human cells.