Modification of the alternative splicing process of testosterone-repressed prostate message-2 (TRPM-2) gene by protein synthesis inhibitors and heat shock treatment.

During the course of the study to examine the effect of cycloheximide on apoptosis-related genes, the variant rat testosterone-repressed prostate message-2 (TRPM-2) mRNA deficient of the exon 5 was found. The putative protein encoded by the variant TRPM-2 mRNA is only constituted from the N-terminal one-third portion of the ordinary TRPM-2 protein. The expression of the variant form was increased dramatically by cycloheximide treatment, while that of the ordinary form was not affected very much. The similar phenomenon was also observed by the use of other types of protein synthesis inhibitors, anisomycin and emetine. The enhancement of expression of the variant was observed in the rat treated with heat shock as well. The variant form was presumably generated by the exon skip mechanism. Systematic analyses of cycloheximide effect on the alternative splicing at various splicing junctions were performed. However, cycloheximide did not exhibit any remarkable effects on other types of alternative splicing, including exon skip in beta A4-amyloid protein precursor (APP) gene, alternative donor selection in Fas antigen gene and alternative acceptor selection in catechol O-methyltransferase (COMT) gene. These results indicated that the induction of exon skip by both protein synthesis inhibition and heat shock treatment occurs in a limited number of genes, if not only in TRPM-2.