REGULATED MRNA TRANSLATION IN DROSOPHILA BODY PATTERNING

果蝇身体模式中的 mRNA 翻译调控

• 批准号: 2900886
• 负责人: Paul M. Macdonald
• 金额: $ 6.04万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2900886
• 关键词: Drosophilidae; binding proteins; body regions; developmental genetics; embryogenesis; gene expression; gene mutation; histogenesis; messenger RNA; molecular cloning

The first steps in animal development, formation of the egg and the beginning of embryogenesis, rely heavily on maternally-synthesized mRNAs. The mother provides the egg with a vast store of mRNAs to support development until the genome of the zygote becomes transcriptionally active and can assume control. Some of these mRNAs actually direct development, providing the embryo with the plans to organize the body plan, or to specify different germ layers. A crucial feature of this strategy is that the maternal mRNAs can be used only at appropriate times and places, so that each region of the embryo receives only the correct instructions. One of the most common mechanisms to control the use of maternal mRNAs involves regulated mRNA translation, and recent advances in the study of Drosophila oogenesis and early embryogenesis have shown that translational regulation play a critical role in the development of that animal. This provides the opportunity to use genetic as well as biochemical approaches to study mechanisms of translational control. We plan to use Drosophila to examine both negative and positive regulation of translation. Both forms of regulation are exerted on the oskar mRNA, a key component in the system that directs posterior body patterning in the oocyte and embryo, and much of our efforts will focus on that mRNA. oskar mRNA is translationally repressed by an ovarian protein, obp80, that binds to multiple sites in the 3' untranslated region of the mRNA. By purifying the obp80 protein and gene, we can apply genetic and biochemical approaches to ask how translational repression is accomplished. Positive control of oskar mRNA translation is provided by the aubergine gene, which is also required for translation of an mRNA (gurken) involved in dorsoventral body patterning. We will identify the features of the oskar and gurken mRNAs that make them dependent on aubergine for translation, and use this information to distinguish between different models of positive translational control. Our progress towards this goal will be aided by identifying other aubergine-dependent mRNAs, and comparing the mRNAs to recognize conserved features. We will also clone the aubergine gene. Neither positive nor negative control of translation is understood in detail, yet both types of regulation appear to be used frequently. In particular, translational regulation is a level of gene expression at which may viruses circumvent or alter host controls or machinery. Thus, our work will provide insights into mechanisms of development and of gene expression, and may ultimately provide insights that facilitate prophylactic or therapeutic solutions to viral infections.

动物发育的第一步，卵的形成和 在胚胎发育的开始，严重依赖于母体合成的mRNA。 母亲为卵子提供了大量的mRNA， 直到受精卵的基因组转录 积极主动，可以控制。其中一些mRNA实际上 发育，为胚胎提供组织身体的计划 计划，或指定不同的胚层。其中一个重要特征是 策略是母体mRNA只能在适当的时候使用 和地方，使每个区域的胚胎只接受正确的 指令控制使用的最常见机制之一 母体mRNAs涉及调控的mRNA翻译， 果蝇卵子发生和早期胚胎发生研究表明， 翻译调控在这一过程中起着关键作用， 动物这就提供了利用基因以及 生物化学方法来研究翻译控制机制。我们 我计划用果蝇来研究基因的负调节和正调节， 翻译.这两种形式的调节都作用于oskar mRNA，这是一个关键。 系统中的一个组件，它引导身体后部的模式， 卵母细胞和胚胎，我们的大部分努力将集中在mRNA上。Oskar mRNA被卵巢蛋白obp80抑制，obp80结合 mRNA 3 '非翻译区的多个位点。通过纯化 obp80蛋白和基因，我们可以应用遗传学和生物化学 方法来询问翻译抑制是如何完成的。积极 Oskar mRNA翻译的控制由茄子基因提供， 也需要翻译的mRNA（gurken）参与 背腹体图案我们将识别奥斯卡的特征 和gurken mRNA，使它们依赖于茄子进行翻译， 并利用这些信息来区分不同型号的 正转译控制我们朝着这一目标的进展将是 通过鉴定其他茄子依赖的mRNA，并比较 mRNA识别保守特征。我们还将克隆茄子 基因翻译的积极控制和消极控制都不被理解 然而，这两种管制似乎都经常使用。在 特别地，翻译调控是基因表达水平， 病毒可以绕过或改变宿主控制或机制。因此，在本发明中， 我们的工作将提供深入了解发展和基因的机制， 表达，并可能最终提供有助于 预防或治疗病毒感染的解决方案。