The Role of the GATA Transcription Factor Gaf1 in Nutrient Responses and Cellular Ageing

The discovery of the biological bases of ageing continues to be one of the most fascinating challenges in modern science. Current efforts have narrowed the complexity of such task by focusing on mechanisms used by the cell to couple its physiology with environmental stimuli as they are often involved in the regulation of ageing. The Target of Rapamycin (TOR) have been proved to be a rheostat of nutritional status orchestrating cellular growth and homeostasis mainly through the regulation of transcriptional responses that remain to be understood. Recent studies unveiled novel functions of the evolutionarily conserved GATA transcription factor Gaf1 in nutrient sensing pathways and potentially in cellular ageing by regulating transcription downstream of TOR signalling. To elucidate these questions, the robust model organism Schizosaccharomyces pombe was used in this study due to its relevant similarity with higher eukaryotes and thoroughly described genetics. The experimental settings involved a combination of in silico analyses, fitness assessments, revivability assays, transcriptomics, mutagenesis, chemical-genetics, and interactome to further characterise functions of Gaf1. This study also contributed to the identification of candidate genes that promote longevity and mediate the resistance of mutant cells depleted of gaf1 gene to the TOR-kinase inhibitor torin1. The results indicate that upon TOR complex 1 (TORC1) inhibition, Gaf1 represses genes that induce protein translation (anabolism) and upregulates genes required for survival (catabolism) under adverse nutritional conditions downstream of TORC1.