The GATA transcription factor Gaf1 represses tRNAs, inhibits growth, and extends chronological lifespan downstream of fission yeast TORC1

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.We thank Nazif Alic for critical reading of the manuscript and Pawan Dhami (Genomics and Genome Engineering Facility, funded by the Cancer Research UK-UCL Centre) for help with sequencing. This research was funded by a Wellcome Trust Senior Investigator Award grant 095598/Z/11/Z and BBSRC project grant BB/R009597/1 (to J.B.) and QR funds and a UEL back-to-the-bench project grant (to C.R.). S.G. was funded by a competitive UEL PhD studentship grant awarded to C.R.Peer reviewe