Multiple cis-acting elements modulate the translational efficiency of GCN4 mRNA in yeast

The expression of the GCN4 gene in yeast is regulated at the translational level: growth of yeast cells under amino acid starvation conditions results in an increase in the translational efficiency of GCN4 mRNA. A sequence within the 5' untranslated region of this mRNA, which contains four small open reading frames, acts in cis to suppress translation when growth occurs in rich media. In this report, we have analyzed the effects on translation of a series of deletion, insertion, and substitution mutations in the 5' untranslated region of GCN4 mRNA. This analysis showed that at least two distinct cis elements located within the region of the small upstream open reading frames are required, in conjunction with trans positive elements, for the translational activation of GCN4 mRNA. We propose that the translational efficiency of GCN4 mRNA is modulated by the rate of translation initiation at the upstream AUG codons.