A mechanism for unsplicing and exon skipping in human alpha- and beta-globin mutant pre-mRNA splicing.

In both of normal human alpha- and beta-globin pre-mRNAs, two introns are spliced correctly, giving mRNA products of (exon 1)-(exon 2)-(exon 3). If 5'-splice site of the second intron is mutated, mRNA of the beta-globin is composed of (exon 1)-(exon 3), skipping the whole exon 2 sequence. However, if 5'-splice site of the second intron is mutated in the alpha-globin, mRNA is (exon 1)-(exon 2)-(intron 2)-(exon 3), unsplicing intron 2. In both of the alpha- and beta-globin pre-mRNAs, strengths of 3'-splice signals of the first and second introns were calculated by the quantification method reported previously, which explains a reason for exon skipping and unsplicing in terms of relative strengths of those signals.