Undergraduate Summer Research Supplement to R35

联系PD/PI：Zid，Brian Matthew 项目摘要/摘要 应激过程中基因调控的一种保守机制是mRNA和 蛋白质进入无膜室，称为信使核糖核蛋白(MRNP)颗粒。 最近的研究表明，这些颗粒的异常形成与多种肿瘤的病理有关。 神经退行性疾病。已经有人提出，mRNAs和蛋白质在这些细胞中的错误定位 病理性包涵体可以通过改变基因表达调控而导致毒性的功能获得。我们的 研究计划旨在利用酵母在葡萄糖饥饿期间形成mRNP颗粒来 阐明这些无膜的形成和功能的基本力学原理 以及应用酵母菌的知识和技术专长来了解 影响神经退行性疾病的RNA结合蛋白的时相分离 哺乳动物细胞中的基因表达。这项研究建立在我们的发现之上，在压力下， 转录和翻译是可以耦合的，因为启动子元素可以决定 将mRNA转化为mRNP颗粒，从而影响了它们随后的可译性。我们的战略将采取 由两部分组成的方法。第一个方向将集中在阐明启动子通过 细胞核中的元件可以将mRNAs定位于细胞质中的mRNP颗粒。 第二，我们将探索这种差异定位对基因表达的作用 酵母和哺乳动物细胞。这项研究将深入了解什么是特定的mRNA的基本问题 定位到无膜室，以及这如何影响细胞的基因表达， 这对于理解有毒的mRNP聚集体在细胞中可能产生的影响是重要的 神经退行性变。 项目摘要/摘要第6页

Contact PD/PI: Zid, Brian Matthew Project Summary/Abstract A conserved mechanism of gene regulation during stress is the phase separation of mRNA and proteins into membrane-less compartments termed messenger ribonucleoprotein (mRNP) granules. Recent research has implicated aberrant formation of these granules in the pathology of a variety of neurodegenerative diseases. It has been proposed that mislocalization of mRNAs and proteins to these pathological inclusions can cause a toxic gain-of-function through altered gene expression control. Our research program aims to use the formation of mRNP granules during glucose starvation in yeast to elucidate basic mechanistic principles about the formation and function of these membrane-less compartments as well as to apply the knowledge and technical expertise from yeast to understand how phase separation of RNA-binding proteins associated with neurodegenerative diseases impinge upon gene expression in mammalian cells. This research builds on our discovery that during stress, transcription and translation can be coupled, as promoter elements can determine the localization of mRNAs to mRNP granules, thereby impinging on their subsequent translatability. Our strategy will take a two-part approach. The first direction will focus on elucidating the mechanism by which promoter elements in the nucleus can direct the localization of mRNAs to mRNP granules in the cytoplasm. Second, we will explore the function that this differential localization has on the gene expression of yeast and mammalian cells. This research will give insight into basic questions of what specifies mRNA localization to membrane-less compartments and how this affects the gene expression of the cell, which is important for understanding the effects that toxic mRNP aggregates may have on cells during neurodegeneration. Project Summary/Abstract Page 6