NSF-MCB/BSF - Composition and Stoichiometry of mRNA-protein Complexes Leading to Nuclear Export and Gene Expression Regulation

NSF-MCB/BSF - 导致核输出和基因表达调控的 mRNA-蛋白质复合物的组成和化学计量

• 批准号: 2140761
• 负责人: Ben Montpetit
• 金额: $ 118.22万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2140761&HistoricalAwards=false
• 关键词: NSF; MCB; BSF; Composition; Stoichiometry

Gene expression in eukaryotic cells (e.g., human or plant cells) requires export of messenger RNA (mRNA) carrying genetic information from the nucleus to the cytoplasm where it can be translated into proteins. In this collaborative project, the PIs will investigate the molecular machinery that enables mRNA transport from one cellular compartment to another in two model systems, yeast (S. cerevisiae) and human cells. The research will increase fundamental understanding of the mechanisms and regulation of gene expression, which is central to knowing how any organism functions in a changing environment. These outcomes can have beneficial societal impacts, e.g., through development of new biotechnology applications. The project will also engage a diverse group of students to provide training, skills, and experiences in scientific research and promote their participation in STEM careers.RNA is a centerpiece of the gene expression pathway that, as a functional unit, is bound by proteins in a ribonucleoprotein particle (RNP). This project focuses on nuclear messenger (m)RNP assembly, which is critical for mRNA export from the nucleus. It is recognized that the protein components of a mRNP are dynamic, and gene-specific mRNPs have varying processing and nuclear export efficiencies, yet it is not known what protein architectures define an export-competent mRNP. The PIs will employ single particle imaging techniques to investigate what protein-mRNA architectures support mRNP export during cell growth and stress in yeast and mammalian systems. They will further characterize the recruitment of mRNP constituents to the site of transcription in order to develop spatial and kinetic models of mRNP assembly. New knowledge expected to emerge from this research includes protein stoichiometry and co-occupancy data for individual mRNPs, information on where and when those proteins are assembled into an mRNP, and identification of transcript features that lead to regulated mRNP export during stress. The outcomes will further understanding of gene expression regulation and how reprogramming mRNP structure-function could support changes in cell function. This collaborative US/Israel project is supported by the US National Science Foundation and the Israeli Binational Science Foundation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

真核细胞（例如人类或植物细胞）中的基因表达需要将携带遗传信息的信使 RNA (mRNA) 从细胞核输出到细胞质，并在细胞质中翻译成蛋白质。在这个合作项目中，PI 将研究在酵母（酿酒酵母）和人类细胞这两个模型系统中使 mRNA 从一个细胞区室转运到另一个细胞区室的分子机制。该研究将增进对基因表达机制和调控的基本了解，这对于了解任何生物体在不断变化的环境中如何发挥作用至关重要。这些成果可以产生有益的社会影响，例如通过开发新的生物技术应用。该项目还将吸引不同的学生群体提供科学研究方面的培训、技能和经验，并促进他们参与 STEM 职业。RNA 是基因表达途径的核心，作为一个功能单位，与蛋白质结合核糖核蛋白颗粒（RNP）。该项目重点关注核信使 (m)RNP 组装，这对于 mRNA 从细胞核输出至关重要。人们认识到 mRNP 的蛋白质成分是动态的，并且基因特异性 mRNP 具有不同的加工和核输出效率，但尚不清楚什么蛋白质结构定义了具有输出能力的 mRNP。 PI 将采用单粒子成像技术来研究在酵母和哺乳动物系统的细胞生长和应激过程中哪些蛋白质-mRNA 结构支持 mRNP 输出。他们将进一步表征 mRNP 成分在转录位点的募集情况，以开发 mRNP 组装的空间和动力学模型。这项研究预计将产生的新知识包括单个 mRNP 的蛋白质化学计量和共占用数据、有关这些蛋白质何时何地组装成 mRNP 的信息，以及识别在应激期间导致调节 mRNP 输出的转录特征。结果将进一步了解基因表达调控以及重编程 mRNP 结构功能如何支持细胞功能的变化。这个美国/以色列合作项目得到了美国国家科学基金会和以色列两国科学基金会的支持。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。