Stress Alters Telomere Length and Telomeric Gene Expression

Abstract

Telomere shortening is an inherent feature of the DNA replication mechanism. Although robust evidence exists for the acceleration of this process under conditions of chronic stress, the molecular and biochemical underpinnings of this process are poorly understood. Here we employ Schizosaccharomyces pombe to establish a model for the effects of chronic environmental stressors on telomere length. We show that environmental stresses alter the growth kinetics of fission yeast and disrupt telomere length homeostasis. Most strikingly, heat and caffeine stress shortened telomeres and ethanol stress elongated telomeres. To investigate changes in gene expression associated with chronic external stresses, we performed total transcriptome sequencing on RNA extracted from cells exposed to these three stress conditions. The RNA-seq data revealed that stress dramatically altered the gene expression profile compared to cells grown under wild-type conditions. Although preliminary data suggests stress changes the expression of telomeric genes, this data is currently being validated by more sensitive quantitative methods. Additionally, we have extended our model in S. pombe to a mammalian system by exposing human foreskin fibroblasts to biological compounds associated with stress in humans and assaying concomitant changes in telomerase activity. We find that treatment with cortisol reduces telomerase activity in this cell line. These findings contribute to the understanding of how chronic stress alters telomere length and gene expression.