Developmental control of mRNPs in C. elegans

在动物发育过程中，不同细胞类型的产生需要特定的蛋白质仅在特定的时间在特定的细胞中变得活跃。许多制造这些蛋白质的mRNAs在细胞质内受到精确的调控。这些mRNAs与许多调控蛋白形成复合体(MRNPs)，这些调控蛋白决定蛋白质合成、mRNA定位和mRNA破坏的速度。发育控制必须调节这些mRNP复合体，但这是如何实现的本质上是一个谜。这个项目将在线虫线虫中探索这个问题，线虫是一个强大的实验系统。在线虫发育的早期，多个RNA结合蛋白在不同的发育阶段控制特定的mRNPs。最近的研究表明，这些mRNPs在卵母细胞分化和早期胚胎发育过程中经历了显着而复杂的转换。这个项目的目标是探索这些转变是如何产生的，并了解发展路径如何控制它们。通过用高分辨率显微镜可以看到的荧光分子标记mRNAs和蛋白质，将直接在卵母细胞和胚胎中检测特定mRNP成分的动态行为。对已知和未知基因的干扰将用于探索已知的发育途径如何影响mRNP的行为，并发现新的mRNP调节因子。这些实验方法可以在线虫中有效地结合，但在大多数其他生物中不能。此外，由于到目前为止发现的所有线虫mRNP成分在人类和其他后生动物中都有对应的成分，这项研究可能会对包括人类在内的大多数多细胞物种共同的基本机制产生新的见解。此外，这项工作可能导致控制对人类、动物和植物疾病重要的基因的新工具。最后，该项目将为研究生和本科生提供科学培训，并将为高中科学推广计划做出贡献。

During animal development, generation of different cell types requires that specific proteins become active only in specific cells at specific times. Many of the mRNAs that make these proteins are precisely regulated within the cell cytoplasm. These mRNAs form complexes (mRNPs) with numerous regulatory proteins that dictate rates of protein synthesis, mRNA localization, and mRNA destruction. Developmental controls must modulate these mRNP complexes, but how this is achieved is essentially a mystery. This project will explore this issue in the nematode C. elegans, a powerful experimental system. During early C. elegans development, multiple RNA-binding proteins control specific mRNPs at distinct developmental stages. Recent studies revealed that these mRNPs undergo remarkable and complex transformations during oocyte differentiation and early embryogenesis. This project's goals are to explore how these transformations arise and to understand how developmental pathways control them. The dynamic behavior of specific mRNP components will be examined directly in oocytes and embryos by tagging mRNAs and proteins with fluorescent molecules that can be seen with high-resolution microscopes. Disruption of both known and unknown genes will be done to explore how known developmental pathways influence mRNP behavior and to discover new mRNP regulators. These experimental methods can be powerfully combined in C. elegans, but not in most other organisms. Furthermore, because all C. elegans mRNP components found to date have counterparts in humans and other metazoans, this study will likely yield new insights into fundamental mechanisms common to most multicellular species including humans. In addition, this work may lead to new tools for controlling genes important for human, animal, and plant disease. Finally, this project will provide scientific training for graduate and undergraduate students, and will contribute to a high school science outreach program.