Study on the induction mechanism of exon skipping and tumorigenesis by 12-repeats

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We found a tandemly repeated 12-nucleotide motif (TGATCTGCCCGT) inserted into the c-myb gene exon 9 in a bovine T-lymphoma cell line BTL-26 which has been established from a calf type of bovine sporadic lymphosarcomas. We investigated the presence of 12-repeat motifs in the other T-lymphoma cell lines from bovine sporadic lymphosarcomas, induction mechanisms of exon 9 skipping in c-myb gene by the 12-repeat motifs and any relationship of turnorigenesis of bovine T-lymphoma and high-transcription-activating activity of c-Myb protein.1. Insertion of a 12-nucleotide motif was found in the c-myb gene exon 9 from three T-lymphoma cell lines (pr1818 and Pr2410) including BTL-26. In addition to 12-repeat, the different 9-nucletide motifs (TCTGGGCGT) was also observed in each cell line. The number of retitive unit ranged from 4 to 17 copies.2. To know whether deficiency in DNA loop repair is involved in the instability of the repeat, abilities to bind and correct the loop structure in nuclear extracts were examined. The data suggest that instability of the 12-repeat in bovine T-lymphoma cells might be independent of deficiency of DNA loop repair function.3. The 12-repeat contained the binding sites (CAACG) for c-Myb and had the ability to transactivate reporter gene in the cells expressing c-Myb or v-Myb.4. It appeared that the deletion of c-myb gene exon 9 was induced by the insertion of the the 12-repeat rather than by the interaction between 12-repeat and c-Myb from the mini-gene plasmid analyses.5. The close relationship between the c-Myb exon 9 skipping and tumorigensesis of bovine T-lymphoma remains unsolved in this study.