RT Journal Article
SR Electronic
T1 Deficiency of the RNA-binding protein Cth2 extends yeast replicative lifespan by alleviating its repressive effects on mitochondrial function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.25.480133
DO 10.1101/2022.02.25.480133
A1 Praveen K. Patnaik
A1 Carine Beaupere
A1 Hanna Barlit
A1 Antonia María Romero
A1 Mitsuhiro Tsuchiya
A1 Michael Muir
A1 María Teresa Martínez-Pastor
A1 Sergi Puig
A1 Matt Kaeberlein
A1 Vyacheslav M. Labunskyy
YR 2022
UL http://biorxiv.org/content/early/2022/02/25/2022.02.25.480133.abstract
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.