SPECIES-SPECIFIC AND TISSUE-SPECIFIC EXPRESSION OF THE C-TERMINAL ALTERNATIVELY SPLICED FORM OF THE TUMOR-SUPPRESSOR P53

Alternative splicing of the p53 transcript which so far has been demonstrated only in the murine system has been proposed as a general regulatory mechanism for the generation of functionally different p53 proteins, We analyzed by RT-PCR the pattern of p53 mRNAs within the region spanning exons In and II of the p53 gene in 13 different tissues from two independent mouse strains, in 10 different rat tissues and in six different human tissues, PCR products of the expected sizes, corresponding to the normally spliced and the alternatively spliced p53 mRNAs, were detected in mice, Alternatively spliced mRNA was found at similar to 25-30% the level of the normally spliced p53 mRNA in most tissues analyzed. In spleen and kidney the proportion of alternatively spliced p53 mRNA was much lower, Surprisingly, examination of p53 mRNAs isolated from 10 different rat tissues and six human tissues within the same region of the p53 gene showed only products of normal size, Although a potential homologous alternative 3' splice site within intron 10 of-the human p53 gene is present in the genomic sequence of human p53, the expected corresponding alternatively spliced p53 mRNA was undetectable, These findings imply that the generation of functionally different forms of p53 by alternative splicing of p53 transcripts is a species-specific event, possibly indicating species-specific mechanisms for regulating p53 activities.