The eIF5 protein plays an important role in the fidelity of AUG start codon selection. However, the hyper GTPase eIF5^G31R 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 GCN4 expression thereby conferring sensitivity to 3-amino-1,2,4-triazole (3AT)-induced starvation. The 3AT sensitivity was rescued by supplementing HIS4^UUG allele. The eIF5^G31R mutant has a better efficiency of UUG codon recognition from the HIS4^UUG allele under starvation conditions. Moreover, the expression of HIS4^UUG allele was significantly lower than the critical level causing additional derepression of GCN4 expression in eIF5^G31R mutant to rescue its 3AT sensitivity. The overexpression of eIF1 improved expression of HIS4^AUG allele and GCN4 transcript causing 3AT resistance, whereas overexpression of eIF1 resulted in diminished UUG codon recognition of HIS4^UUG allele causing 3AT sensitivity, despite having higher GCN4 expression. This paper reports the critical role of HIS4 expression necessary in response to 3AT-induced starvation in the eIF5^G31R mutant which is ostensibly not a direct target of 3AT inhibition.

• PMID: 30262708
• PubMed
• PubTator

Reference Type

Journal Article

Authors

Charles Antony A, Alone PV

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