RIM15 deletion has a very strong impact on calorie-restricted S. cerevisiae.
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Rim15 coordinates cell cycle arrest and robustness during calorie-restricted growth.
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The nature and intensity of regulation by Rim15 depend on nutritional status.
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Retentostat cultures of yeast provide a model for post-mitotic mammalian cells.
Abstract
The PAS kinase Rim15 is proposed to integrate signals from different nutrient-sensing pathways and to control transcriptional reprogramming of Saccharomyces cerevisiae upon nutrient depletion. Despite this proposed role, previous transcriptome analyses of rim15 mutants solely focused on growing cultures. In the present work, retentostat cultivation enabled analysis of the role of Rim15 under severely calorie-restricted, virtually non-growing conditions. Under these conditions, deletion of RIM15 affected transcription of over 10-fold more genes than in growing cultures. Transcriptional responses, metabolic rates and cellular morphology indicated a key role of Rim15 in controlled cell-cycle arrest upon nutrient depletion. Moreover, deletion of rim15 reduced heat-shock tolerance in non-growing, but not in growing cultures. The failure of rim15 cells to adapt to calorie restriction by entering a robust post-mitotic state resembles cancer cell physiology and shows that retentostat cultivation of yeast strains can provide relevant models for healthy post-mitotic and transformed human cells.
Abbreviations
CFU
colony forming units
EDGE
empirical analysis of digital gene expression data in R v 1.1.291
