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, Zhen Zhou, O'Laughlin, Richard, Yuting Liu, Yang Li, Wanying Tian, Hetian Su, Yanfei Jiang, Holness, Shayna E., Stasiowski, Elizabeth, Tsimring, Lev S., Pillus, Lorraine, Hasty, Jeff, and Nan Hao
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RNA-binding proteins , *RIBOSOMAL proteins , *CHROMATIN , *RIBOSOMAL RNA , *RECOMBINANT DNA , *RIBOSOMAL DNA - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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