1. Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis
- Author
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Paxman, Julie, Zhou, Zhen, O'Laughlin, Richard, Liu, Yuting, Li, Yang, Tian, Wanying, Su, Hetian, Jiang, Yanfei, Holness, Shayna E, Stasiowski, Elizabeth, Tsimring, Lev S, Pillus, Lorraine, Hasty, Jeff, and Hao, Nan
- Subjects
Genetics ,Aging ,1.1 Normal biological development and functioning ,Underpinning research ,Generic health relevance ,Silent Information Regulator Proteins ,Saccharomyces cerevisiae ,Saccharomyces cerevisiae Proteins ,Proteostasis ,Chromatin ,Sirtuin 2 ,Lysine ,Saccharomyces cerevisiae ,DNA ,Ribosomal ,RNA ,Ribosomal ,RNA-Binding Proteins ,single-cell aging ,proteostasis ,time-lapse imaging ,chromatin stability ,microfluidics ,S ,cerevisiae ,S. cerevisiae ,cell biology ,computational biology ,systems biology ,Biochemistry and Cell Biology - Abstract
Chromatin instability and protein homeostasis (proteostasis) stress are two well-established hallmarks of aging, which have been considered largely independent of each other. Using microfluidics and single-cell imaging approaches, we observed that, during the replicative aging of Saccharomyces cerevisiae, a challenge to proteostasis occurs specifically in the fraction of cells with decreased stability within the ribosomal DNA (rDNA). A screen of 170 yeast RNA-binding proteins identified ribosomal RNA (rRNA)-binding proteins as the most enriched group that aggregate upon a decrease in rDNA stability induced by inhibition of a conserved lysine deacetylase Sir2. Further, loss of rDNA stability induces age-dependent aggregation of rRNA-binding proteins through aberrant overproduction of rRNAs. These aggregates contribute to age-induced proteostasis decline and limit cellular lifespan. Our findings reveal a mechanism underlying the interconnection between chromatin instability and proteostasis stress and highlight the importance of cell-to-cell variability in aging processes.
- Published
- 2022