Translational regulation of GCN4 in yeast by upstream ORFs. Unphosphorylated eIF2, present when nutrients are abundant, leads to frequent translation initiation at upstream ORFs (uORFS) and little initiation at the GCN4 gene (first three steps). When eIF2α is phosphorylated, translation initiation in general, including at the uORFs, is reduced; initiation at GCN4 is now more likely (last two steps).