Ribosome biogenesis in the eukaryotic cell

核糖体代表细胞制造蛋白质的“工厂”，因此是不可或缺的细胞子结构。 更好地了解这个“工厂”、它的功能以及它的合成方式不仅具有根本意义，而且具有从生物技术到医学研究的许多潜在应用。 我们的研究重点是核糖体 RNA，它占核糖体质量的一半，并已被证明代表蛋白质合成中的活跃“机器”。 我们建议进一步询问核糖体RNA的合成和组装成核糖体的方式，以及如何应用“质量控制”来避免对细胞非常有害甚至致命的无功能核糖体。 过去的研究表明，rRNA 转录本中间隔区之间的相互作用对于 rRNA 的有效加工以及核糖体成熟至关重要。 我们开发了一个模型，其中 rRNA 加工代表核糖体生物发生过程中的质量控制机制，其中 rRNA 转录物不同区域之间的相互作用有助于确保只有功能性 RNA 掺入成熟核糖体中。 我们还鉴定了一种蛋白质复合物，一种核糖体组装伴侣（RAC），它与间隔区相互作用以组织适当的处理域。 在进一步的资助下，我们建议继续对 RAC 蛋白复合物、其在间隔区域内的相互作用位点以及它如何促进核糖体生物发生进行表征。 核苷酸修饰也将作为第二种质量控制机制进行检查，并且将继续研究控制核糖体生物发生的调节机制。 鉴于核糖体在细胞功能和生长中的核心作用，此类研究很容易有望为人类健康或农业做出贡献。 例如，许多药物和农药已经并将继续以核糖体或核糖体合成为目标。 研究生将继续参与这项研究的各个方面，以提供最大程度的培训

The ribosome represents a cell's "factory" for making protein and, as such, is an indispensable cellular substructure. A better understanding of this "factory", its function and how it is synthesized is not only of fundamental interest but has many potential applications ranging from biotechnology to medical research. Our research is focused on ribosomal RNA which makes up half the ribosome mass and has been demonstrated to represent the active "machinery" in protein synthesis. We propose to ask further questions about the way the ribosomal RNA is synthesized and assembled into ribosomes as well as how "quality control" is applied to avoid non functional ribosomes that can be very detrimental or even lethal to the cell. Past studies indicate that interactions between the spacer regions in rRNA transcripts are critical to the efficient processing of rRNA as well as ribosome maturation. We have developed a model in which rRNA processing represents a mechanism for quality control during ribosome biogenesis, where the interactions between different regions of the rRNA transcripts help assure that only functional RNAs are incorporated into mature ribosomes. We also have identified a protein complex, a ribosome assembly chaperone (RAC) which interacts with the spacer regions to organize the appropriate processing domain. With further funding we propose to continue our characterization of the RAC protein complex, its sites of interaction within the spacer regions and how it acts to facilitate ribosome biogenesis. Nucleotide modifications also will be examined as a second quality control mechanism and studies will continue on regulatory mechanisms that control ribosome biogenesis. Given the ribosome's central role in cell function and growth, such studies might easily be expected to contribute to human health or agriculture. Many drugs and pesticides, for example, have and will continue to target ribosomes or ribosome synthesis. Graduate students will continue to participate in all aspects of this research in order to provide maximum levels of training