Journal
CELL REPORTS
Volume 40, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.111113
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This study reveals that defects in the mRNA-binding protein Cth2 contribute to iron dys-homeostasis, aging, and lifespan regulation in yeast. Modulation of Cth2 activity can impact mitochondrial function and extend lifespan.
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, Cth2 deficiency re-lieves Cth2-mediated post-transcriptional repression of nuclear-encoded components of the electron trans-port 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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