Biochemical and Genetic Characterization of Ribosome Biogenesis and Functional Diversity

* 核糖体是一种复杂的分子机器，在将遗传密码翻译成蛋白质的过程中起着核心作用。在面包酵母中，核糖体RNA* 的组装需要大量的因子和137个核糖体 * 蛋白编码基因的正确表达，其中大多数是重复基因。在脊椎动物和酵母中，导致前体rRNA加工、组装和输出的事件已经被广泛研究，整个过程已经非常清楚。然而，调节重复 * 核糖体蛋白基因表达的机制及其对核糖体生物发生和功能 * 的影响仍不清楚。最近，我们发现大多数核糖体 * 蛋白旁系同源物的表达并不相同，并且在大多数情况下，它们以正常生长所需的特定比例表达。这一发现反驳了核糖体蛋白基因旁系同源物的平等和多余的作用。在 * 这个提议中，我们的目标是了解调节重复基因表达 * 的机制及其对核糖体产生和功能的影响。因此，我们提出两个具体目标：1。确定调节重复核糖体蛋白基因表达的机制。在这个目标下，我们将确定复制的基因是如何交流的，以建立核糖体蛋白的整体表达。我们最近发现了一组相互调节的重复核糖体基因，我们将使用它们作为本研究的模型。将监测启动子、内含子、转录终止和细胞核糖核酸酶对这些旁系同源物表达的影响，并鉴定影响基因间和基因内调控的元件。这项研究的结果不仅将解释核糖体蛋白的表达是如何协调的，而且还将帮助我们理解基因调控的一般机制的重要组成部分。2.了解复制基因对核糖体生物发生和功能的影响。在这个目标下，我们将监测改变核糖体蛋白质的比例对核糖体蛋白质的影响。

* **Ribosomes*are intricate molecular machines that play a central role in translating the*genetic code into proteins. In baker's yeast, assembly of the ribosomal RNA*requires a large number of factors and the correct expression of 137 ribosomal*protein-coding genes the majority of which are duplicated genes. The events*leading to the processing of pre-rRNAs, assembly and export have been*extensively studied in vertebrates and yeast, and the overall process is very*well understood. However, the mechanism regulating the expression of duplicated*ribosomal protein genes and its impact on ribosome biogenesis and function*remain unclear. Recently, we discovered that the majority of the ribosomal*protein paralogs are not expressed equally and that in most cases they are*expressed in a specific ratio required for normal growth. This finding argues*against an equal and redundant role for the ribosomal protein genes paralogs. In*this proposal, we aim at understanding the mechanism regulating the expression*of duplicated genes and its impact on ribosome production and function. Accordingly,*we propose two specific aims: 1. Determine the mechanism regulating the*expression of duplicated ribosomal protein genes. Under this aim, we will*determine how duplicated genes communicate to establish the overall expression*of ribosomal proteins. We have recently identified a set of inter-regulated*duplicated ribosomal genes, and we will use them as a model for this study. The*impact of promoters, intron, transcription termination and cellular*ribonucleases on the expression of these paralogs will be monitored and*elements that affect inter and intragene regulation will be identified. The*outcome of this study will not only explain how the expression of ribosomal*proteins is coordinated but will also help us to understand an important*component of the general mechanism of gene regulation. 2. Understand the*impact of duplicated genes on ribosome biogenesis and function. Under this*aim, we will monitor the impact of changing the ratio of ribosomal proteins on*ribos