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

真核细胞(如人类或植物细胞)的基因表达需要携带遗传信息的信使RNA(MRNA)从细胞核输出到细胞质，在细胞质中可以翻译成蛋白质。在这个合作项目中，PI将在两个模型系统(酵母(S.cerevisiae)和人类细胞)中研究使mRNA从一个细胞室转移到另一个细胞室的分子机制。这项研究将增加对基因表达机制和调控的基本了解，这是了解任何有机体如何在不断变化的环境中发挥作用的核心。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职业生涯。RNA是基因表达途径的核心，作为一个功能单位，它由核糖核蛋白颗粒(RNP)中的蛋白质结合。这个项目的重点是核信使(M)RNP组装，这是从细胞核输出mRNA的关键。人们认识到mRNP的蛋白质组分是动态的，基因特异性的mRNP具有不同的加工和核出口效率，但尚不清楚什么蛋白质结构定义了具有出口能力的mRNP。PI将使用单粒子成像技术来研究在酵母和哺乳动物系统中，在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组分在转录位点的招募，以开发mRNP组装的空间和动力学模型。预计这项研究将产生新的知识，包括单个mRNP的蛋白质化学计量学和共占数据，关于这些蛋白质在哪里以及何时组装成mRNP的信息，以及识别导致应激期间受调控的mRNP输出的转录特征。这些结果将进一步了解基因表达调控以及重新编程mRNP结构功能如何支持细胞功能的变化。这一美国/以色列合作项目得到了美国国家科学基金会和以色列双国科学基金会的支持。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.