The role of the Drosophila TIS11 protein in the regulation of mRNA turnover

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The Drosophila Tis11 gene is differentially spliced to produce four separate transcripts and two proteins. The transcripts are expressed in all developmental stages from early embryo to the adult, although there are minor differences in the levels of expression at different stages. Insertion mutations that seem to eliminate the gene product cause a delay in development, poor viability, and defects in the extremities among the survivors, while over expression may cause early death. Deletion mutations have been generated by imprecise excision of one of the P element insertions next to the Tis11 promoter. This insertion mutation carries a promoter that reads in the same direction as Tis11 transcription and when induced increases the level of Tis11 transcript. As this insertion is fully viable, and other insertions are lethal, deletions were expected to be lethal as well. We found, however, that the lethal mutations recovered all deleted one of the two adjacent genes. Thus, deletions of Tis11 are not expected to be lethal. In addition, duplications for these neighboring genes rescue the deletion mutations, but not the insertion mutations, suggesting that the insertions have second-site lethal mutations. Another imprecise excision scheme is now underway to delete the conserved zinc finger domain without assuming that these new mutations will be lethal.