Neuron-specific splicing of C-SRC RNA in human brain

The C-SRC, C-YES, and FYN genes encode three closely related tyrosine protein kinases that are expressed in human neural tissues. A unique form of the C-SRC gene has been demonstrated to be expressed in avian and murine brain tissues as the result of alternative splicing between the third and fourth exons. This neuronal-specific splicing event adds to the C-SRC mRNA an 18 base pair exon capable of encoding the same six amino acids in both avian and murine neural tissues. The C-YES and FYN genes share with C-SRC similar exon-intron boundaries and a high degree of amino acid sequence homology in the 3/4 exon coding region. However, potential alternative splicing of the C-YES and FYN genes in this region has not been previously investigated. In this study we have compared the expression of C-SRC, C-YES, and FYN RNAs in human lung, liver, brain, and placenta tissues and prepared cDNA clones spanning exons 3 and 4 for each of these genes from the different tissues. Sequence analysis of these cDNA clones revealed that the splicing patterns for the FYN and C-YES genes were the same among the various tissues, whereas C-SRC cDNAs isolated from brain contained 18 additional bases with the capacity to code for the same six amino acids present in the neural-specific forms of avian and murine pp60c-src.