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

Article


Rodríguez-López, M., Gonzalez Gonoggia, S., Hillson, O., Tunnacliffe, E., Codlin, S., Tallada, V. A., Bähler, J. and Rallis, C. 2020. The GATA Transcription Factor Gaf1 Represses tRNAs, Inhibits Growth, and Extends Chronological Lifespan Downstream of Fission Yeast TORC1. Cell Reports. 30 (10), pp. 3240-3249.e4.
AuthorsRodríguez-López, M., Gonzalez Gonoggia, S., Hillson, O., Tunnacliffe, E., Codlin, S., Tallada, V. A., Bähler, J. and Rallis, C.
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.

JournalCell Reports
Journal citation30 (10), pp. 3240-3249.e4
ISSN2211-1247
Year2020
PublisherElsevier (Cell Press)
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Anyone
Supplemental file
Supplemental file
Supplemental file
Digital Object Identifier (DOI)doi:10.1016/j.celrep.2020.02.058
Web address (URL)https://doi.org/10.1016/j.celrep.2020.02.058
Publication dates
Online10 Mar 2020
Publication process dates
Accepted13 Feb 2020
Deposited17 Mar 2020
FunderWellcome Trust Senior Investigator Award
Biotechnology and Biological Sciences Research Council (BBSRC)
University of East London (UEL)
Copyright holder© 2020 The Authors
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The GATA transcription factor Gaf1 represses tRNA genes, inhibits growth, and extends chronological lifespan downstream of fission yeast TORC1
Rodríguez-López, M., Gonzalez, S., Hillson, O., Tunnacliffe, E., Codlin, S., Tallada, V. A., Bähler, J. and Rallis, C. The GATA transcription factor Gaf1 represses tRNA genes, inhibits growth, and extends chronological lifespan downstream of fission yeast TORC1.