Sequence features affecting translation initiation in eukaryotes: A bioinformatic approach

Abstract

Sequence features play an important role in the regulation of translation initiation. This thesis focuses on the sequence features affecting eukaryotic initiation. The characteristics of 5' untranslated region in Saccharomyces cerevisiae were explored. It is found that the 40 nucleotides upstream of the start codon is the critical region for translation initiation in yeast. Moreover, this thesis attempted to solve some controversies related to the start codon context. Two key nucleotides in the start codon context are the third nucleotide upstream of the start codon (-3 site) and the nucleotide immediately following the start codon (+4 site). Two hypotheses regarding +4G (G at +4 site) in Kozak consensus, the translation initiation hypothesis and the amino acid constraint hypothesis, were tested. The relationship between the -3 and +4 sites in seven eukaryotic species does not support the translation initiation hypothesis. The amino acid usage at the position after the initiator (P1' position) compared to other positions in the coding sequences of seven eukaryotic species was examined. The result is consistent with the amino acid constraint hypothesis. In addition, this thesis explored the relationship between +4 nucleotide and translation efficiency in yeast. The result shows that +4 nucleotide is not important for translation efficiency, which does not support the translation initiation hypothesis. This work improves our current understanding of eukaryotic translation initiation process.