Department of Chemistry, Faculty of Science, Hokkaido University
Translation initiation signal in mRNA has been usually given by the AUG intiation codon. However, longer nucleotide sequence including not only the AUG codon but also 5'-untranslated sequence is found to determine the position of initiation. Mathematical approach of quantification analysis was made with nucleotide sequences of translation initiation signal in 698 vertebrate mRNAs, which were compiled by Kozak. Our approach was then applied to human alpha-globin mRNA, where the authentic signal sequence at position (37/38) was found to possess the strongest signal. This can explain the reason why its position was selected as the actual initiation site in the alpha-globin mRNA. In this mRNA, a mutant of alpha-thalassemia has been reported where dinucleotide deletion (AC) took place at position (-3$@!A(J-2) from the AUG codon in the 5'-untranslated region. Experimental results show that this deletion causes significant decrease in the efficiency of translation initiation. Such a behaviour was well explained by our analysis.