cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila
cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila
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DOI：
10.1016/j.cub.2007.02.027
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发表时间：
2007-04-03
期刊：
影响因子：
9.2
通讯作者：
Schupbach, Trudi
中科院分区：
文献类型：
--
作者：
Chen, Yu;Pane, Attilio;Schupbach, Trudi
配子发生是所有生物体中高度调节的过程。在果蝇中，减数分裂检查点监测双链DNA断裂，并涉及果蝇ATR和Chk 2协调减数分裂细胞周期与建立卵和胚胎轴的信号事件。检查点活性调节转化生长因子-α样Gurken信号分子的翻译，其诱导卵泡细胞中的背侧细胞命运[1-3]。我们发现果蝇基因cutoff（cuff）的突变影响生殖细胞包囊的发育，并导致Grk蛋白表达减少而导致腹侧化的卵。令人惊讶的是，袖口突变导致两个逆转录转座因子，Het-A和Tart的转录水平显着增加。我们发现，对roo元件的小干扰RNA仍然产生在袖口突变卵巢。这些结果表明，Cuff参与了rasiRNA途径，并且最有可能在siRNA生物合成的下游起作用。cuff突变体的蛋壳和产蛋缺陷被chk 2突变抑制。我们还发现，与rasiRNA通路有关的另一个基因aubergine（aub）的突变被chk 2突变显著抑制。我们的研究结果表明，rasiRNA途径中的突变体导致生殖系中的转座事件升高，并且这种升高激活了一个检查点，导致生殖细胞的损失和剩余卵室中Gurken蛋白的减少。
Gametogenesis is a highly regulated process in all organisms. In Drosophila, a meiotic checkpoint which monitors double-stranded DNA breaks and involves Drosophila ATR and Chk2 coordinates the meiotic cell cycle with signaling events that establish the axis of the egg and embryo. Checkpoint activity regulates translation of the transforming growth-factor-alpha-like Gurken signaling molecule which induces dorsal cell fates in the follicle cells [1-3]. We found that mutations in the Drosophila gene cutoff (cuff) affect germline cyst development and result in ventralized eggs as a result of reduced Grk protein expression. Surprisingly, cuff mutations lead to a marked increase in the transcript levels of two retrotransposable elements, Het-A and Tart. We found that small interfering RNAs against the roo element are still produced in cuff mutant ovaries. These results indicate that Cuff is involved in the rasiRNA pathway and most likely acts downstream of siRNA biogenesis. The eggshell and egg-laying defects of cuff mutants are suppressed by a mutation in chk2. We also found that mutations in aubergine (aub), another gene implicated in the rasiRNA pathway, are significantly suppressed by the chk2 mutation. Our results indicate that mutants in rasiRNA pathways lead to elevated transposition incidents in the germline, and that this elevation activates a checkpoint that causes a loss of germ cells and a reduction of Gurken protein in the remaining egg chambers.