GENETICS AND BIOCHEMISTRY OF RIBOSOME BIOSYNTHESIS

核糖体，蛋白质合成的基本机制， 显然在细胞生长中起着关键作用， 与细胞增殖的调节密切相关， 在原核和真核细胞中。 众所周知在 在细菌中，核糖体的细胞含量大致与 在各种营养条件下细胞的生长速度。 我们的目标是了解细菌如何调节细菌的产生 核糖体及其生长速率。 我们之前发现 核糖体蛋白质合成和核糖体组装 当核糖体蛋白质合成超过 核糖体生物合成的速率，某些关键的核糖体蛋白质作用于 作为抑制剂，阻止其自身的进一步翻译， mRNA。 该反馈调节模型可以解释 大多数核糖体的协调和平衡合成 蛋白质成分 此外，我们最近发现， rRNA（和tRNA）的合成受到负反馈调节， rRNA操纵子，核糖体的产物，而阴性 反馈信号（尚未确定）可能是 由核糖体的过度翻译活动产生。 这 rRNA合成的反馈调节解释了生长- 核糖体合成的速率依赖性控制。 我们将继续 研究翻译反馈的详细机制 核糖体蛋白质合成的调节，以及那些参与 rRNA合成的反馈调节。 体内和 将使用体外方法。 体内方法将包括 分离具有翻译调节缺陷的突变体， 那些在生长速率依赖性rRNA控制中有缺陷的 合成. 此外，我们会研究规管 合成以及RNA聚合酶和其他 参与转录和翻译的蛋白质因子 与生长调节有关的装置。 最后， 我们现在打算研究核糖体合成的调节， 酵母 我们计划分离RNA的温度敏感突变体 聚合酶I及其抑制剂。 对这些突变体的研究， 以及与RNA聚合酶I相关的因子和结构 将完成了解rRNA（和核糖体）的调节 在酵母细胞和真核细胞中的合成。

The ribosome, the machinery essential for protein synthesis, obviously plays a key role in cell growth and its synthesis is intimately connected to the regulation of cell proliferation both in prokaryotic and eukaryotic cells. It is well known that in bacteria, the cellular content of ribosomes is roughly proportional to the growth rate of cells under various nutritional conditions. Our goal is to understand how bacteria regulate the production of ribosomes and their growth rate. We have previously discovered that ribosomal protein synthesis and ribosome assembly are coupled such that when ribosomal protein synthesis exceeds the rate of ribosome biosynthesis, certain key ribosomal proteins act as inhibitors that prevent the further translation of their own mRNA. This feedback regulation model can account for coordinate and balanced synthesis of most of the ribosomal protein components. In addition, we have recently found that the synthesis of rRNA (and tRNA) is negatively feedback regulated by products of rRNA operon, ribosomes, and that the negative feedback signal (which is yet to be identified) is probably generated by excess translational activities of ribosomes. This feedback regulation of rRNA synthesis accounts for the growth- rate-dependent control of ribosome synthesis. We will continue to study detailed mechanisms involved in the translational feedback regulation of ribosomal protein synthesis, and those involved in the feedback regulation of rRNA synthesis. Both in vivo and in vitro approaches will be used. In vivo approaches will include isolation of mutants with defects in translational regulation and those with defects in growth-rate-dependent control of rRNA synthesis. In addition, we will study the regulation of the synthesis as well as the function of RNA polymerase and other protein factors involved in the transcription and translation apparatus in connection with the regulation of growth. Finally, we now intend to study the regulation of ribosome synthesis in yeast. We plan to isolate temperature-sensitive mutants of RNA polymerase I and their suppressors. Studies on these mutants as well as factors and structures associated with RNA polymerase I will be done to understand the regulation of rRNA (and ribosome) synthesis in yeast cells and in eukaryotic cells in general.