Quantification analysis of 5'-splice signal sequences in mRNA precursors. Mutations in rabbit beta-globin gene.

Concerning the signals which direct excision of introns from mRNA precursors in genes of higher eukaryotes, a consensus sequence composed of nine nucleotides, CAAG/GTAGAGT, has been proposed for the 5'-splice site, but actual 5'-splice site sequences differ from it to a greater or lesser degree. In the present paper, the 5'-splice site sequence of the rabbit beta-globin gene was analyzed using a quantification method (categorical discriminant analysis). In this method, each 9-nucleotide sequence in the pre-mRNA was characterized by its sample score, which shows the extent to which the sequence contains the signal. This approach could explain not only the location of the 5'-splice site, but also the experimental results of various point mutations in the 5'-splice region, as reported by Aebi et al. Our method further predicted the positions of cryptic 5'-splice sites, which are activated when the authentic 5'-splice site is abolished.