Excessive rDNA Transcription Drives the Disruption in Nuclear Homeostasis during Entry into Senescence in Budding Yeast

• DOI: 10.1016/j.celrep.2019.06.032
• Publication Date: 2019-07-09T14:40:33Z
• Authors: Sandrine Morlot; Jia Song; Isabelle Léger-Si...; Audrey Matifas; Olivier Gadal; Gilles Charvin
• Keywords: Senescence; Budding yeast; Transcription; Homeostasis; Budding

Highlights•Single-cell monitoring shows that ERC accumulation starts well before senescence•ERC drives a large upregulation in pre-rRNA, but not ribosome, synthesis•A strong loss of nuclear homeostasis occurs downstream nucleolar defects•Rejuvenation daughters is ensured by asymmetrical partitioningSummaryBudding yeast cells undergo limited number divisions they enter senescence and die. Despite recent mechanistic advances, whether how molecular events are temporally causally linked during the transition to remain elusive. Here, using real-time observation extrachromosomal rDNA circles (ERCs) single cells, we provide evidence ERCs build up rapidly with exponential kinetics any physiological decline. We then show fuel massive increase ribosomal RNA (rRNA) levels nucleolus, which do mature into functional ribosomes. This breakdown coordination followed homeostasis, thus defining chronology related leading cell death. A computational analysis supports model series age-independent processes lead an age-dependent mortality, hence explaining emergence aging budding yeast.Graphical abstract