The GCN4 gene encodes a positive regulator of unlinked amino acid biosynthetic genes in yeast. I present evidence that the GCN4 gene is itself regulated by amino acid availability and that the regulation occurs at the translational level. A GCN4-lacZ fusion was used as a measure of the expression of GCN4 gene product. Starvation for histidine leads to derepression of the fusion enzyme in the wild type but not in a gcn2- strain. The gcn2- mutation does not reduce fusion transcript levels relative to wild type, suggesting that the product of GCN2 functions as an activator of GCN4 translation. The GCN4 transcript has a 5' leader that is approximately equal to 600 nucleotides long and contains four small open reading frames. A deletion of the small open reading frames results in constitutive derepression of fusion enzyme levels as the result of an approximately equal to 10-fold increase in the efficiency of translation of the fusion transcript. The deletion suppresses the requirement for GCN2 function. These results suggest that the GCN4 5' leader acts in cis to repress GCN4 translation and that GCN4 translation increases in response to amino acid starvation as the result of GCN2 antagonism of the repressing sequences in the GCN4 5' leader.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|