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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 S. 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.
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Protein interaction potential landscapes for yeast replicative aging
Abstract We proposed a novel interaction potential landscape approach to map the systems-level profile changes of gene networks during replicative aging inSaccharomyces cerevisiae. This approach enabled us to apply quasi-potentials, the negative logarithm of the probabilities, to calibrate the elevation of the interaction landscapes with young cells as a reference state. Our approach detected opposite landscape changes based on protein abundances from transcript levels, especially for intra-essential gene interactions. We showed that essential proteins play different roles from hub proteins on the age-dependent interaction potential landscapes. We verified that hub proteins tend to avoid other hub proteins, but essential proteins prefer to interact with other essential proteins. Overall, we showed that the interaction potential landscape is promising for inferring network profile change during aging and that the essential hub proteins may play an important role in the uncoupling between protein and transcript levels during replicative aging.
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- PAR ID:
- 10219367
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Scientific Reports
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2045-2322
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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