Analysis of microtubule localized RNAs

6.摘要 这项提案的长期目标是确定目标为 有丝分裂微管的特异性RNA及定位RNA在有丝分裂中的作用 和发展。在细胞分裂过程中遗传物质的稳定遗传对 所有有机体的生存和分化。RNA在细胞内具有广泛的功能，作用于 既可以作为以信使核糖核酸形式存在的遗传信息，也可以作为各种基因的结构和催化成分 蛋白质复合体。通过对mRNAs和非编码RNA的转录后调控 转运到特定的亚细胞位置是一种广泛使用的调节基因表达的机制 在时间和空间上。将不同类型的rna定位于有丝分裂纺锤体是一项极好的测试。 了解定位的mRNAs如何控制有丝分裂纺锤体功能和遗传 遗传物质。这项建议将使用体外和体内试验相结合的方法来鉴定 顺式作用的定位序列，靶向特定的有丝分裂纺锤体在减数分裂和 在整个发展过程中。这一信息将大大增加已知的 本地化元素，并提供为从头开始建立准确模型所需的信息 预测定位的RNA。关于信使核糖核酸定位元件的信息将被用于 生化纯化和鉴定负责RNA转运的反式作用蛋白因子 微管，增加了对用于将特定RNA输送到 细胞或生物体内的隐蔽位置。最后，mRNAs的身份定位于有丝分裂 纺锤体提示，局部翻译可能在各种有丝分裂事件的调控中发挥重要作用。 这项建议将研究有丝分裂转换在细胞周期调节中的作用，这将提供 洞察细胞周期的翻译控制。这项提案将提供第一个全面的 对定位于特定亚细胞结构的mRNAs的分析将提供对系统的洞察 用于信使核糖核酸的本地化，并提供有关本地化的信使核糖核酸在 细胞周期控制。这里描述的实验方法将通常适用于 了解本地化RNA在各种细胞过程中的影响。7.项目叙事 这个项目的目标是了解mrna的本地化如何影响微管。 细胞分裂过程中的组装和染色体分离。这项研究可能会让我们的 对与人类疾病密切相关的细胞分裂机制的理解 比如癌症和唐氏综合症。更好地理解细胞分裂的机制 可能导致药物设计的改进，这可能会影响人类健康。

6. Abstract The long-term goal of this proposal is to identify the cis and trans acting systems that target specific RNAs to mitotic microtubules and to understand the function of localized RNAs during mitosis and development. The stable inheritance of genetic material during cell division is critical for the survival and differentiation of all organisims. RNA serves a wide variety of functions within cells, acting both as genetic information in the form of mRNA, and as a structural and catalytic component of various protein complexes. Posttranscriptional regulation of both mRNAs and noncoding RNAs through transport to specific subcellular locations is a widely used mechanism for modulating gene expression in time and space. The localization of different types of RNA to the mitotic spindle is an excellent test case for understanding how localized mRNAs control mitotic spindle function and the inheritance of genetic material. This proposal will use a combination of in vitro and in vivo assays to identify both the cis acting localization sequences that target specific mRNAs to the mitotic spindle during meiosis and throughout development. This information will provide a large increase in the number of known localization elements and provide the information required to build accurate models for the de novo prediction of localized RNAs. Information about mRNA localization elements will be used to biochemically purify and identify trans acting protein factors responsible for the transport of RNA to microtubules, increasing the understanding of the types of systems used to transport specific RNAs to discreet locations within a cell or organism. Finally, the identities of mRNAs localized to the mitotic spindle suggest that localized translation might play a major role in regulation of various mitotic events. This proposal will examine the role of mitotic translation in cell cycle regulation, which will provide insight into translational control of the cell cycle. This proposal will provide the first comprehensive analysis of mRNAs localized to a specific subcellular structure, will provide insight into the systems utilized for mRNA localization, and provide information about the functional role of localized mRNAs in cell cycle control. The experimental approach described here will be generally applicable to understanding the impact of localized RNAs in various cellular processes. 7. Project Narrative The goal of this project is to understand how localization of mRNAs affects microtubule assembly and chromosome segregation during cell division. This study is likely to inform our understanding of the mechanisms of cell division, which are intimately linked to human diseases such as cancer and Down's syndrome. Greater understanding of the mechanisms cell division may lead to improved drug design that could impact human health.