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

Area of Science:

• Molecular Biology
• Systems Biology
• Genetics

Background:

• Cellular processes exhibit inherent stochasticity, leading to cell-to-cell variation in protein abundance, commonly referred to as noise.
• While noise has been modeled, its functional significance and implications for cellular robustness remain largely unexplored.

Approach:

• Revisiting established noise models to identify key determinants of gene expression variability.
• Analyzing transcription levels in yeast to understand their relationship with protein abundance noise.
• Comparing transcriptional programs across diverse organisms, including Escherichia coli, yeast, and human cells.

Key Points:

• The number of messages transcribed per cell cycle is identified as the critical factor determining noise levels.
• This quantity quantitatively predicts both the magnitude and non-canonical scaling of noise with protein abundance in yeast.
• A conserved minimum transcription level of one message per cell cycle acts as a lower floor, ensuring robustness for essential genes.

Conclusions:

• A conserved transcriptional program, with a minimum of one message per gene per cell cycle, exists across Escherichia coli, yeast, and human.
• Robustness to noise is a central evolutionary strategy influencing the expression levels of essential genes.
• This fundamental optimal strategy for managing gene expression noise is conserved from prokaryotes to eukaryotes.