Splice-site signals of mRNA precursors as revealed by computer search. Site-specific mutagenesis and thalassemia.

Many eukaryotic genes are interrupted by introns, which are removed from mRNA precursors by the RNA splicing mechanism. Although nucleotide sequences around splice sites have considerable homology among various genes, exact splice-site signals are unknown. Previously, applying the computer searching method to primary nucleotide sequences of various genes, we studied what kinds of patterns are the necessary and sufficient sequences for recognition of the 5'-slice site (donor site). We proposed that four common patterns, AG/GTA, /GTAAGT, RG/GTGAG, and AG/GTXXGT, where R = A or G and X = A, T, G, or C, are often used as such signals. In the present paper, we examined a number of experimental results on site-specific mutagenesis around donor sites and on alpha- and beta-thalassemia in globin genes, and found that the above four common patterns could explain almost all of those results.