mRNA assembly in Drosophila germ granules

果蝇胚芽颗粒中的mRNA组装 每一个物种的发育都严重依赖于空间组织的信使RNA(MRNAs)。事实上，即使是一个 单个不对称分布的mRNA可以指定细胞的形态、发育中的体型 后生动物的有机体和细胞谱系。RNA结合蛋白(RBP)通常组织mRNAs和 把他们招募到亚细胞结构。然而，mRNAs也可以自组织成多个mRNAs组装。 独立于其他蜂窝组件。在不同物种的健康细胞中发现了mrna组装。 通常与RNA颗粒有关，无膜核蛋白(RNP)颗粒调节 MRNAs的翻译和稳定性。信使核糖核酸组装也是人类重复发病的一个标志 扩张性疾病，如强直性肌营养不良1(MD1)、肌萎缩侧索硬化症(ALS)和 脊髓小脑性共济失调(SCA)。这些发现表明，信使核糖核酸的组装是信使核糖核酸的固有属性。 这可能是与生物相关的。然而，mRNA的确切机制和潜在的生物学功能 组装情况尚不清楚。已经证明，mRNA可以通过相分离进行自组装，这一过程类似于石油和天然气。 水的分离。这里，RNA：RNA相互作用，促进分子间(反式)碱基配对和 二级(顺)RNA结构被认为与驱动mRNA组装有关。此外，体外数据 提示作为rna颗粒核心成分的rna解旋酶被认为能溶解rna： 颗粒中的相互作用。根据这些发现，出现了几个关键问题。MRNAs是如何 在旨在阻止RNA：RNA相互作用的颗粒中自组装？信使核糖核酸组装体的作用是什么？ 核糖核酸颗粒？反式和顺式RNA的作用是什么：RNA相互作用和RNA解旋酶在 信使核糖核酸组件和核糖核酸颗粒的形成和功能这项研究的五年目标是 回答这些问题，确定信使核糖核酸的机制和生物学功能 在果蝇胚芽颗粒中组装。信使核糖核酸组装体倾向于形成小的簇状， 对浓度和它们形成的环境敏感。因此，中国面临的核心挑战 研究信使核糖核酸组装是必须采用的方法，使这一过程的检查 活体，具有高分辨率和高灵敏度。我们将使用遗传和定量的超分辨率 分析完整细胞及其自然细胞内信使核糖核酸组装的成像方法 背景。我们的目标是揭示生物体如何利用信使核糖核酸组装来促进 以及mRNA组装的错误调控如何导致人类疾病，如MD1， ALS和SCA。

mRNA ASSEMBLY IN DROSOPHILA GERM GRANULES Development of every species relies critically on spatially organized messenger RNAs (mRNAs). Indeed, even a single asymmetrically distributed mRNA can specify the morphology of cells, the body plan of a developing organism and cell lineages across metazoans. RNA binding proteins (RBPs) typically organize mRNAs and recruit them to subcellular structures. However, mRNAs can also self-organize into multi-mRNA assemblies independently of other cellular components. mRNA assemblies are found in healthy cells in different species and are often associated with RNA granules, membraneless ribonucleoprotein (RNP) particles that regulate translation and stability of mRNAs. mRNA assemblies are also a hallmark of pathogenesis in human repeat expansion disorders such as myotonic dystrophy 1 (MD1), amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia (SCA). These findings indicate that mRNA assembly is an inherent property of an mRNA that could be biologically relevant. However, the exact mechanism and potential biological functions of mRNA assembly is unclear. mRNAs have been shown to self-assemble by phase separation, a process akin to oil-and- water de-mixing. Here, RNA:RNA interactions, which promote intermolecular (trans) base-pairing and secondary (cis) RNA structures have been implicated in driving mRNA assembly. In addition, in vitro data suggest that RNA helicases, which are core constituents of RNA granules are thought to dissolve RNA:RNA interactions in granules. In light of these findings, several critical questions arise. How do mRNAs self-assemble in granules designed to prevent RNA:RNA interactions? What is the role of mRNA assemblies in RNA granules? What is the function of trans and cis RNA:RNA interactions and RNA helicases in the formation and function of mRNA assemblies and RNA granules? The five-year goal of this study is to answer these questions and determine the mechanism and biological function of mRNA assembly in Drosophila germ granules. mRNA assemblies tend to form as small clusters that are acutely sensitive to the concentration and the environment in which they form. Thus, the central challenge in studying mRNA assembly is that methods must be employed that enable examination of this process in vivo and with high resolution and sensitivity. We will use genetic and quantitative, super-resolution imaging approaches to analyze mRNA assembly in intact cells and within their natural cellular context. We aim to uncover new insight into how organisms harness mRNA assemblies to promote development and how misregulation of mRNA assembly could contribute to human diseases, such as MD1, ALS and SCA.