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Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis
- Publication Year :
- 2022
- Publisher :
- eScholarship, University of California, 2022.
-
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.
- Subjects :
- 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
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7390565de28c9cee00d7665579630c10