High-energy guanine nucleotides as a signal capable of linking growth to cellular energy status via the control of gene transcription

Abstract

This mini-review considers the idea that guanylate nucleotide energy charge acts as an integrative signal for the regulation of gene expression in eukaryotic cells and discusses possible routes for that signal's transduction. Gene expression is intimately linked with cell nutrition and diverse signaling systems serve to coordinate the synthesis of proteins required for growth and proliferation with the prevailing cellular nutritional status. Using short pathways for the inducible and futile consumption of ATP or GTP in engineered cells of Saccharomyces cerevisiae, we have recently shown that GTP levels can also play a role in determining how genes act to respond to changes in cellular energy supply. This review aims to interpret the importance of GTP as an integrative signal in the context of an increasing body of evidence indicating the spatio-temporal complexity of cellular de novo purine nucleotide biosynthesis.

Keywords: GTP; Guanylate energy charge; Metabolism; Regulation.

Fig. 1

Exploring the effects of increased use of the energy stored in ATP or GTP on gene transcription in the budding yeast Saccharomyces cerevisiae (Hesketh et al. 2019). The inducible heterologous expression of bacterial enzymes forms futile shunt pathways to AMP or GMP (a) capable of influencing intracellular nucleotide composition and gene transcription (b). Data interpretation alongside published information on the correlation of anabolic gene transcription with nucleosome remodeling (Machné and Murray ; Nocetti and Whitehouse 2016) suggests GTP/GEC as an integrative signal linking growth to energy status (c)