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Status |
Public on Jul 18, 2022 |
Title |
Deficiency of the RNA-binding protein Cth2 extends yeast replicative lifespan by alleviating its repressive effects on mitochondrial function |
Organism |
Saccharomyces cerevisiae |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Iron dyshomeostasis contributes to aging, but little information is available about the molecular mechanisms. Here, we provide evidence that, in Saccharomyces cerevisiae, aging is associated with altered expression of genes involved in iron homeostasis. We further demonstrate that defects in the conserved mRNA-binding protein Cth2, which controls stability and translation of mRNAs encoding iron-containing proteins, increase lifespan by alleviating its repressive effects on mitochondrial function. Mutation of the conserved cysteine residue in Cth2 that inhibits its RNA-binding activity is sufficient to confer longevity, whereas Cth2 gain-of-function shortens replicative lifespan. Consistent with its function in RNA degradation, we demonstrate that Cth2 deficiency relieves Cth2-mediated post-transcriptional repression of nuclear-encoded components of the electron transport chain. Our findings uncover a major role of the RNA-binding protein Cth2 in the regulation of lifespan and suggest that modulation of iron starvation signaling can serve as a target for potential aging interventions.
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Overall design |
RNA-Seq and Ribo-Seq analyses of replicatively aged (OLD) and young (YNG) wild-type and cth2 knockout strains
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Contributor(s) |
Patnaik PK, Beaupere C, Barlit H, Labunskyy VM |
Citation(s) |
35858543 |
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Submission date |
Nov 22, 2021 |
Last update date |
Aug 26, 2022 |
Contact name |
Vyacheslav Labunskyy |
E-mail(s) |
vlabuns@bu.edu
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Organization name |
Boston University School of Medicine
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Department |
Department of Dermatology
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Lab |
Labunskyy Lab
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Street address |
609 Albany St
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02118 |
Country |
USA |
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Platforms (1) |
GPL13821 |
Illumina HiSeq 2000 (Saccharomyces cerevisiae) |
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Samples (15)
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GSM5698682 |
wild-type RNA-seq, old, replicate 2 |
GSM5698683 |
wild-type Ribo-seq, young, replicate 1 |
GSM5698684 |
wild-type Ribo-seq, young, replicate 2 |
GSM5698685 |
wild-type Ribo-seq, old, replicate 1 |
GSM5698686 |
wild-type Ribo-seq, old, replicate 2 |
GSM5698687 |
cth2Δ RNA-seq, young, replicate 1 |
GSM5698688 |
cth2Δ RNA-seq, young, replicate 2 |
GSM5698689 |
cth2Δ RNA-seq, old, replicate 1 |
GSM5698690 |
cth2Δ Ribo-seq, young, replicate 1 |
GSM5698691 |
cth2Δ Ribo-seq, young, replicate 2 |
GSM5698692 |
cth2Δ Ribo-seq, old, replicate 1 |
GSM5698693 |
cth2Δ Ribo-seq, old, replicate 2 |
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Relations |
BioProject |
PRJNA782500 |
SRA |
SRP347195 |
Supplementary file |
Size |
Download |
File type/resource |
GSE189306_RAW.tar |
690.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector![Help](/coreweb/images/long_help4.gif) |
Raw data are available in SRA |
Processed data provided as supplementary file |
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