PT  - JOURNAL ARTICLE
AU  - Praveen K. Patnaik
AU  - Carine Beaupere
AU  - Hanna Barlit
AU  - Antonia María Romero
AU  - Mitsuhiro Tsuchiya
AU  - Michael Muir
AU  - María Teresa Martínez-Pastor
AU  - Sergi Puig
AU  - Matt Kaeberlein
AU  - Vyacheslav M. Labunskyy
TI  - Deficiency of the RNA-binding protein Cth2 extends yeast replicative lifespan by alleviating its repressive effects on mitochondrial function
AID  - 10.1101/2022.02.25.480133
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.25.480133
4099  - http://biorxiv.org/content/early/2022/02/25/2022.02.25.480133.short
4100  - http://biorxiv.org/content/early/2022/02/25/2022.02.25.480133.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.