Coupling of GCN4 mRNA translational activation with decreased rates of polypeptide chain initiation

The steady-state translational activation of the GCN4 mRNA is based upon an increase in the rate of ribosome initiation at the protein coding AUG following translation of the 5' most proximal open reading frame located in its untranslated region. Such an increase is effected when the cellular amount of the GCN2 protein kinase is increased or when the function of the GCD1 gene product is defective. Here, we report conditions that result in a dramatic transient increase in the rate of GCN4 protein synthesis, which also requires the prior translation of the 5' most proximal open reading frame but is independent of the GCN2 protein. This activation of GCN4 mRNA translation coincides with a decrease in the rate of total cellular protein synthesis. We also observed low rates of protein synthesis in the gcd1 strain and in strains that overexpress the GCN2 protein kinase. The process in protein synthesis that is affected is formation of 43S preinitiation complexes. These results reveal the existence of a coupling between this process in translational initiation and the mechanism that activates translation of GCN4 mRNA.