Quantification Analysis of 3'-Splice Signal Sequences in mRNA Precursors. Mutations and Exon Skipping in Rabbit .BETA.-Globin Gene.

The signals which direct excision of introns from mRNA precursors in mammalian genes have been studied. The consensus sequence for the 3′-splice site is (T or C)11N(C or T) AG/G, where N is A, G, C or T, and where the stroke (/) indicates the boundary between intron and exon. In the present research, the nucleotide sequence at the 3′-splice junction in rabbit β-globin gene was analyzed by a quantification method proposed previously. Using a sample score of 16-nucleotide sequence at the 3′-splice junction, we proposed the strength of the 3′-splice signal. This approach could explain not only the location of the authentic 3′-splice sites in rabbit β-globin pre-mRNA but also the experimental results of various point mutations introduced into the 3′-splice region of the second intron. Our analysis also explains a skipping mechanism of the second exon, in which the first exon is spliced directly to the third exon if the 5′-splice site of the second intron is destroyed.

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