The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan

Mittal, Nitish and Guimaraes, Joao C. and Gross, Thomas and Schmidt, Alexander and Vina-Vilaseca, Arnau and Nedialkova, Danny D. and Aeschimann, Florian and Leidel, Sebastian A. and Spang, Anne and Zavolan, Mihaela. (2017) The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan. Nature Communications, 8 (457). pp. 1-12.

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In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Spang)
05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Spang, Anne and Zavolan, Mihaela and Azevedo Salgado Guimaraes, Joao Carlos and Schmidt, Alexander and Zavolan, Mihaela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 May 2020 11:12
Deposited On:04 Oct 2017 12:25

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