Ribosomal mutation in helix 32 of 18S rRNA alters fidelity of eukaryotic translation start site selection.

The 40S ribosome plays a critical role in start codon selection. To gain insights into the role of its 18S rRNA in start codon selection, a suppressor screen was performed that suppressed the preferential UUG start codon recognition (Suppressor of initiation codon: Sui phenotype) associated with the eIF5 mutant. The C1209U mutation in helix h32 of 18S rRNA was found to suppress the Sui and Gcn (failure to derepress GCN4 expression) phenotype of the eIF5 mutant.

Fidelity of start codon selection influences 3-amino-1,2,4-triazole sensitivity in GTPase activating protein function defective eIF5.

The eIF5 protein plays an important role in the fidelity of AUG start codon selection. However, the hyper GTPase eIF5 mutation in yeast causes preferential utilization of UUG as initiation codon and is termed as suppressor of initiation codon (Sui) phenotype. The eIF5G31R mutant recognizes upUUG initiation codon from the 5' regulatory leader region of GCN4 transcript and dominantly represses expression thereby conferring sensitivity to 3-amino-1,2,4-triazole (3AT)-induced starvation.

Defect in the GTPase activating protein (GAP) function of eIF5 causes repression of GCN4 translation.

In eukaryotes, the eIF5 protein plays an important role in translation start site selection by providing the GAP (GTPase activating protein) function. However, in yeast translation initiation fidelity defective eIF5 mutant causes preferential utilization of UUG as initiation codon and is termed as Suppressor of initiation codon (Sui) phenotype due to its hyper GTPase activity. The eIF5 mutant dominantly represses GCN4 expression and confers sensitivity to 3-Amino-1,2,4-Trizole (3AT) induced starvation.