Gene Products that Mediate Translation Initiation in Yeast

Abstract

The general mechanism proposed for higher eukaryotic translation initiation is illustrated by a scanning model (Kozak 1980) in which the preinitiation complex recognizes the 5′ end of capped mRNA, migrates along the 5′ leader region until the first AUG initiator codon is encountered, where translation begins. Some of the features associated with the yeast initiator regions from over 130 genes were analyzed (Cigan and Donahue 1987). Yeast leader regions are rich in adenine nucleotides, have an average length of 52 nucleotides, and are void of stable stem-loop structures. The sequence context flanking the start codon of yeast mRNAs ${\rm{(5' - }}\frac{{\rm{A}}}{{\rm{Y}}}{\rm{A}}\frac{{\rm{A}}}{{\rm{U}}}{\rm{A}}\underline {{\rm{AUG}}} {\rm{UCU - 3')}}$ is different from the higher eukaryotic consensus (5′-CACCAUGG-3′) with the exception of a preference for an A nucleotide at the -3 position relative to the AUG start codon. 95% of yeast mRNAs utilize the AUG codon nearest the 5′ end of message as the start site for translation. Converse genetic experiments at the CYC1 gene (Sherman and Stewart 1982) and the HIS4 gene (Donahue and Cigan 1988) in yeast establish the preference for the first AUG codon relative to the 5′ end of the message to serve as the start site of translation. The “first AUG” rule observed at CYC1 and HIS4 (Cigan et al. 1988b), in conjunction with the basic features of the leader region of yeast mRNAS, is consistent with a scanning mechanism being utilized for translation initiation in yeast.