Deficiency of the RNA-binding protein Cth2 extends yeast replicative lifespan by alleviating its repressive effects on mitochondrial function.

Autor:	Patnaik PK; Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA., Beaupere C; Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA., Barlit H; Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA., Romero AM; Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain., Tsuchiya M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA., Muir M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA., Martínez-Pastor MT; Departamento de Bioquímica y Biología Molecular, Universitat de València, Valencia, Spain., Puig S; Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain., Kaeberlein M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA., Labunskyy VM; Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: vlabuns@bu.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Jul 19; Vol. 40 (3), pp. 111113.
DOI:	10.1016/j.celrep.2022.111113
Abstrakt:	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 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 Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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