Department of Chemistry, Faculty of Science, Hokkaido University,
Sapporo 060, Japan
Concerning the translation initiation signals in vertebrate mRNAs, not only ATG initiation codon but also sequences flanking the initiation codon are required to direct the position of initiation. A consensus sequence for the signal, (GCC)GCCGCCATGG, has been proposed by Kozak, but actual initiation sequences differ from it in a greater or lesser degree. In the present report, the translation initiation signal sequences of human beta-globin and beta-thalassemia mRNAs were analyzed using a quantification method proposed previously. In this method, each 16-nucleotide sequence in the mRNA was charactarized by its sample score, which shows intensity of the signal. Scoring of signal sequences could explain not only the authentic initiation site but also the experimental results of various mutations which took place around the initiation site. Further analysis demonstrated that, in addition to the signal intensity, the sequence nearest the cap site was preferred. This supported Kozak's scanning hypothesis, in which the eukaryotic small ribosomal subunit binds initially at the 5'-end of mRNA and subsequently migrates to the signal sequence.