| Autor: |
Julie Paxman, Zhen Zhou, Richard O’Laughlin, Yang Li, Wanying Tian, Hetian Su, Yanfei Jiang, Shayna E. Holness, Elizabeth Stasiowski, Lev S. Tsimring, Lorraine Pillus, Jeff Hasty, Nan Hao |
| Rok vydání: |
2021 |
| Popis: |
SummaryChromatin instability and loss of protein homeostasis (proteostasis) 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, proteostasis decline occurred specifically in the fraction of cells with decreased stability at the ribosomal DNA (rDNA) region. 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. We further found that loss of rDNA stability contributes to age-dependent aggregation of rRNA-binding proteins through aberrant overproduction of rRNAs. These aggregates negatively impact nucleolar integrity and global proteostasis and hence limit cellular lifespan. Our findings reveal a mechanism underlying the interconnection between chromatin instability and proteostasis decline and highlight the importance of cell-to-cell variability in aging processes. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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