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

果蝇Tis11基因的差异剪接产生四个独立的转录本和两个蛋白质。转录本在从早期胚胎到成体的所有发育阶段中表达，尽管在不同阶段的表达水平存在微小差异。插入突变似乎消除了基因产物，导致发育延迟，生存能力差，以及幸存者四肢的缺陷，而过度表达可能导致过早死亡。通过不精确切除Tis11启动子旁边的P元件插入之一来产生缺失突变。该插入突变携带与Tis11转录方向相同的启动子，并且在诱导时增加Tis11转录物的水平。由于这种插入是完全可行的，而其他插入是致命的，因此预期缺失也是致命的。然而，我们发现，致命的突变恢复了所有删除的两个相邻基因之一。因此，预期Tis11的缺失不会致死。此外，这些相邻基因的重复挽救了缺失突变，但不能挽救插入突变，这表明插入具有第二位点致死突变。另一个不精确的切除计划正在进行中，删除保守的锌指结构域，而不假设这些新的突变将是致命的。

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.