Extending the dynamic range of transcription factor action by translational regulation

TL;DR

This paper proposes a novel mechanism where transcription factors regulate gene expression indirectly via mRNA binding, reducing noise and extending the dynamic range of regulation, inspired by homeodomain proteins like Bicoid.

Contribution

It introduces a scheme where TFs act as translational regulators by binding mRNA, enhancing information flow and noise reduction in gene regulation.

Findings

Translational regulation reduces noise in TF action.

The scheme outperforms direct regulation under certain conditions.

Homeodomain proteins may utilize this mechanism for effective regulation.

Abstract

A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these molecules at their binding sites can severely limit the precision of regulation. Recent work on the optimization of information flow through regulatory networks indicates that the lower end of the dynamic range of concentrations is simply inaccessible, overwhelmed by the impact of this noise. Motivated by the behavior of homeodomain proteins, such as the maternal morphogen Bicoid in the fruit fly embryo, we suggest a scheme in which transcription factors also act as indirect translational regulators, binding to the mRNA of other transcription factors. Intuitively, each mRNA molecule acts as an independent sensor of the TF concentration, and averaging over these multiple sensors reduces the noise. We analyze information flow through this new scheme and identify conditions under which it outperforms direct transcriptional regulation. Our results suggest that the dual role of homeodomain proteins is not just a historical accident, but a solution to a crucial physics problem in the regulation of gene expression.