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The GATA Transcription Factor Gaf1 Represses tRNAs, Inhibits Growth, and Extends Chronological Lifespan Downstream of Fission Yeast TORC1

Rodríguez-López, María and Gonzalez, Suam and Hillson, Olivia and Tunnacliffe, Edward and Codlin, Sandra and Tallada, Victor A and Bähler, Jürg and Rallis, Charalampos (2020) 'The GATA Transcription Factor Gaf1 Represses tRNAs, Inhibits Growth, and Extends Chronological Lifespan Downstream of Fission Yeast TORC1.' Cell Reports, 30 (10). 3240 - 3249.e4. ISSN 2211-1247

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Abstract

Target of Rapamycin Complex 1 (TORC1) signaling promotes growth and aging. Inhibition of TORC1 leads to reduced protein translation, which promotes longevity. TORC1-dependent post-transcriptional regulation of protein translation has been well studied, while analogous transcriptional regulation is less understood. Here we screen fission yeast mutants for resistance to Torin1, which inhibits TORC1 and cell growth. Cells lacking the GATA factor Gaf1 (gaf1Δ) grow normally even in high doses of Torin1. The gaf1Δ mutation shortens the chronological lifespan of non-dividing cells and diminishes Torin1-mediated longevity. Expression profiling and genome-wide binding experiments show that upon TORC1 inhibition, Gaf1 directly upregulates genes for small-molecule metabolic pathways and indirectly represses genes for protein translation. Surprisingly, Gaf1 binds to and downregulates the tRNA genes, so it also functions as a transcription factor for RNA polymerase III. Thus, Gaf1 controls the transcription of both protein-coding and tRNA genes to inhibit translation and growth downstream of TORC1.

Item Type: Article
Uncontrolled Keywords: S. pombe; cell growth; aging; transcription factor; RNA polymerase III; protein translation; vacuole; TOR; GATA6; tRNA
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 18 Mar 2020 11:32
Last Modified: 18 Mar 2020 12:15
URI: http://repository.essex.ac.uk/id/eprint/27122

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