Gcn4 (ATF4) drives a methionine-dependent anabolic program by enabling metabolic precursor supply [article]

Rajalakshmi Srinivasan, Adhish S Walvekar, Aswin Sai Narain Seshasayee, Sunil Laxman
2020 bioRxiv   pre-print
How cells manage biomolecule supply to enable constructive metabolism for growth is a fundamental question. Methionine directly activates genomic programs where translation and metabolism are induced. In otherwise amino acid limitations, methionine induced ribosomal biogenesis, carbon metabolism, amino acid and nucleotide biosynthesis. Here, we find that the methionine-induced anabolic program is carbon-source independent, and requires the starvation-responsive transcription factor Gcn4/ATF4.
more » ... factor Gcn4/ATF4. Integrating transcriptome and ChIP-Seq analysis, we decipher direct and indirect, methionine-dependent roles for Gcn4. Methionine-induced genes enabling metabolic precursor biosynthesis critically require Gcn4; contrastingly ribosomal genes are partly repressed by Gcn4. Gcn4 binds promoter-regions and transcribes a subset of metabolic genes, driving amino acid (particularly lysine and arginine) biosynthesis. This sustained lys/arg supply maintains high translation capacity, by allowing the translation of lys/arg enriched transcripts, notably the translation machinery itself. Thus, we discover how Gcn4 enabled metabolic-precursor supply bolsters protein synthesis demand, and drive a methionine-mediated anabolic program.
doi:10.1101/2020.01.29.924274 fatcat:fpzfazppardlnl4j75as45cgta