The mechanics and dynamics of RNP granules

 描述(申请人提供)：这项提案的长期目标是了解肋状核蛋白(RNP)颗粒的分子机制。RNP颗粒存在于多种细胞中，通常与RNA代谢有关。在许多后生动物的生殖细胞中，特殊的RNP颗粒，称为胚粒，是细胞分化为功能配子所必需的。秀丽隐杆线虫胚芽颗粒，P-颗粒，是种系维持所必需的。P-颗粒组装需要线虫。特定的支架蛋白，PGL-1和PGL-3，以及高度保守的VASA相关死盒解旋酶，GLH-1和GLH-4。VASA解旋酶存在于所有后生动物中，是哺乳动物生育所必需的。本方案以P-颗粒为模型，研究细菌颗粒的组装和功能。我将研究PGL和GLH蛋白在RNA加工和颗粒形成中的机制作用，并研究P颗粒的分子功能。在此过程中，我将学习RNA测序、线虫基因组编辑和单分子显微镜的新方法，使我能够在体外和体内分析和测试我的结构模型。R00阶段将继续使用这些方法来探索与组装动力学和RNA代谢相关的P-颗粒的生物学功能。P颗粒的基本机制无疑将有助于深入了解生殖颗粒在组织发育中的作用，以及更全面地了解RNP颗粒如何在细胞生物学中发挥作用。

 DESCRIPTION (provided by applicant): The long-term goal of this proposal is to understand the molecular mechanisms of Rib nucleoprotein (RNP) granules. RNP granules are found in a diversity of cells and are typically involved in RNA metabolism. In germ cells of many metazoans, specialized RNP granules, known as germ granules, are required for cell differentiation into functional gametes. The Caenorhabditis elegans germ granule, the P-granule, is required for germline maintenance. P-granule assembly requires the Caenorhabditis sp. specific scaffold proteins, PGL-1 and PGL-3, and the highly conserved Vasa-related DEAD-box helicases, GLH-1 and GLH-4. Vasa helicases are found in all metazoans and are necessary for fertility in mammals. This proposal uses the P-granule as a model to study the assembly and function of germ granules. I will study the mechanistic roles of the PGL and GLH proteins in RNA processing and granule formation, and investigate the molecular function of P-granules. Along the way, I will learn new methods in RNA sequencing, C. elegans genome editing, and single molecule microscopy, enabling me to analyze and test my structural models in vitro and in vivo. The R00 phase will continue using these methods to probe the biological function of P-granules related to assembly dynamics and RNA metabolism. The basic mechanisms of P-granules will undoubtedly provide insight into the function of germ granules in tissue development and a greater overall understanding how RNP granules function in cell biology.