Gene overexpression reveals alternative mechanisms that induce GCN4 mRNA translation.

The Saccharomyces cerevisiae GCN4 gene which encodes the transcription activator Gcn4, is under translational regulation. Derepression of GCN4 mRNA translation is mediated by the Gcn2 protein kinase which phosphorylates the alpha subunit of eIF-2, upon amino-acid starvation. Here, we report that overexpression of certain Saccharomyces cerevisiae genes generates intracellular conditions that alleviate the requirement for a functional Gcn2 kinase to induce GCN4 mRNA translation. Our findings, combined with the fact that Gcn2 kinase is dispensable during the initiation phase of the cellular response to amino-acid limitation, provide the grounds to further elucidate the mechanisms underlying the physiology of this homeostatic response.