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

核糖体是微小的分子机器，在所有细胞中存在数十万个。 它们在生命的各个方面都发挥着重要作用，因为它们是基因组（或DNA）和蛋白质之间的联系。 核糖体“读取”遗传信息并将其翻译成相应的蛋白质。 反过来，蛋白质为细胞提供建筑和结构支持，运动（如肌肉收缩）的能力，并且通常本身充当微型分子马达，为细胞提供使用能量，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蛋白质的理解越来越复杂，就像我们对汽车内燃机的理解一样。 这里提出的研究着眼于核糖体是如何组装的，以及另一种微型分子机器，称为SSU加工体，它组装核糖体的一部分。 这类似于我说我的兴趣是汽车如何组装和汽车装配线如何工作。 核糖体是由一种特殊类型的遗传物质核糖体RNA组装而成的，也含有许多蛋白质。 核糖体RNA必须被制造和切割，同时与蛋白质组装以产生成熟的核糖体。 拟议的具体目标1着眼于核糖体RNA同时制造、切割和组装的机制，而不是作为单独的事件。 用汽车组装来类比，这类似于用本身未完成的零件组装汽车。 在整个非常复杂的核糖体组装过程中，有许多步骤必须被监控。 正如在《特定目标2》中所提出的，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实现的。 这个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，这类似于更快或更慢地装配汽车，或者告诉工人在汽车上涂更多或更少的油漆。 这项工作有可能使所有加拿大人受益匪浅。 核糖体组装是所有细胞中的关键基本过程。 它影响着所有的生物学，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牲畜。 我希望这项研究能让我们更好地理解核糖体组装复杂过程中的许多步骤。 反过来，这可能使我们能够操纵核糖体组装以增加作物和牲畜产量，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.