Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis
| Autor: | Zhen Zhou, Julie Paxman, Richard O'Laughlin, Yuting Liu, Yang Li, Wanying Tian, Hetian Su, Yanfei Jiang, Shayna E Holness, Elizabeth Stasiowski, Lev S Tsimring, Lorraine Pillus, Jeff Hasty, Nan Hao |
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| Rok vydání: | 2022 |
| Předmět: |
Aging
Saccharomyces cerevisiae Proteins chromatin stability 1.1 Normal biological development and functioning microfluidics S. cerevisiae time-lapse imaging Saccharomyces cerevisiae DNA Ribosomal General Biochemistry Genetics and Molecular Biology Sirtuin 2 computational biology Silent Information Regulator Proteins Underpinning research cell biology Genetics cerevisiae Silent Information Regulator Proteins Saccharomyces cerevisiae Ribosomal proteostasis General Immunology and Microbiology General Neuroscience Lysine RNA-Binding Proteins systems biology General Medicine DNA Chromatin RNA Ribosomal single-cell aging Proteostasis RNA Generic health relevance Biochemistry and Cell Biology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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