Molecular characterization of the function and regulation of the subcomplexes of the ribosomal small subunit processome in ribosome assembly in the yeast model organism Saccharomyces cerevisiae

核糖体是一种微小的分子机器，存在于所有细胞中的数十万人。它们在生活的方方面面都扮演着至关重要的角色，因为它们是连接基因组(或DNA)和蛋白质的纽带。核糖体“读取”遗传信息，并将其翻译成相应的蛋白质。反过来，蛋白质为细胞提供结构和结构支持、移动能力(如肌肉收缩)，并通常本身充当微型分子马达，为细胞提供利用能量、生长和分裂的能力。这些都是细胞正常日常生活的关键方面。我们对核糖体如何读取遗传物质并组装相应的蛋白质有了越来越复杂的理解，就像我们很好地理解汽车的内燃机一样。这里提出的研究着眼于核糖体是如何组装的，以及另一种名为SSU Procedome的微型分子机器，它组装部分核糖体。这就像我说的，我的兴趣是汽车是如何组装的，汽车装配线是如何工作的。核糖体是由一种名为核糖体RNA的特殊遗传物质组装而成的，它还含有许多蛋白质。核糖体RNA必须被制造和切割，同时与蛋白质组装成成熟的核糖体。拟议的具体目标1着眼于核糖体RNA同时合成、切割和组装的机制，而不是作为单独的事件。使用汽车组装类比，这类似于将本身未完成的部件组装成汽车。在核糖体组装的非常复杂的过程中，有许多步骤必须监控。这通常是通过在组装核糖体的蛋白质中添加一种称为磷酸基团的小化学物质来完成的，如特定目标2中所建议的那样。这种磷酸基团可以打开或关闭这些蛋白质。参考我们的汽车装配线模型，这类似于组装汽车的速度或快或慢，或告诉工人在汽车上多涂或少涂漆。这项工作有可能极大地造福所有加拿大人。核糖体组装是所有细胞的一个关键的基本过程。它影响到所有的生物学，从生态学到人类健康(想想所有的癌症和许多遗传疾病)，再到农业中的作物生产和畜牧业。我预计这项研究将使我们更好地了解核糖体组装的复杂过程中的许多步骤。反过来，这可能允许我们操纵核糖体组装以增加作物和畜牧业产量，并在核糖体组装出现缺陷时进行干预。

Ribosomes are tiny molecular machines that are present by the hundreds of thousands in all cells. They play an essential role in every aspect of life, as they are the link between the genome (or DNA) and proteins. Ribosomes “read” genetic information and translate it into the corresponding protein. In turn, proteins provide the cell with architectural and structural support, the ability to move (such as muscle contraction), and often themselves act as miniature molecular motors in providing the cell with the ability to use energy, to grow, and to divide. These are all key aspects to the normal day-to-day life of a cell. We have an increasingly sophisticated understanding of how ribosomes read genetic material and assemble the corresponding protein, much like we understand well the internal combustion motor of a car. The research proposed here looks at how the ribosome is assembled and at another miniature molecular machine, called the SSU processome, which assembles part of the ribosome. That is akin to my saying that my interests are in how cars are assembled and how car assembly lines work.Ribosomes are assembled from a special type of genetic material called ribosomal RNA and also contain many proteins. The ribosomal RNA has to be made and cut, and is at the same time assembled with proteins to give a mature ribosome. The proposed Specific Aim 1 looks at mechanisms by which ribosomal RNA is made, cut and assembled at the same time instead of as separate events. Using the car assembly analogy, this is akin to assembling a car from pieces that are themselves unfinished.Throughout the very complicated process of ribosome assembly are numerous steps that must be monitored. This is typically done, as proposed in Specific Aim 2, by the addition of a small chemical, called a phosphate group, to proteins working on assembling ribosomes. This phosphate group turns these proteins on or off. Referring to our car assembly line model, this is akin to assembling cars faster or slower, or telling the workers to put more paint or less paint on the car.This work has the potential to greatly benefit all Canadians. Ribosome assembly is a key fundamental process in all cells. It influences all of biology, from ecology to human health (think all cancers and many genetic disorders) to crop production and livestock in agriculture. I anticipate that this research will allow us to better understand the many steps in the complicated process of ribosome assembly. In turn, this may allow us to manipulate ribosome assembly to increase crop and livestock production and also to intervene when ribosome assembly becomes defective.