RIBOSOMAL GENES OF YEAST AND THEIR REGULATION

生物学的一个根本挑战是理解 一个细胞的操作，导致它精确地加倍，所有它的 组件在单个世代中。我们对生物合成的研究 酿酒酵母中的核糖体导致了 出人意料的发现，核糖体的重点取决于 细胞膜的持续合成。我们的观点是，这 表示的是不同的 细胞的大分子成分，必须存在的电路 确保平衡增长，但这一点通常没有得到承认。 这一核糖体合成过程需要协调合成 RRNA来自100多个基因，核糖体蛋白来自更多 而不是75个基因。对其规则的研究导致了深刻的 生物学的洞察力。这项提议将把遗传和生化结合起来 探索膜合成之间调节回路的技术 和核糖体合成的问题：膜上的缺陷如何 合成会产生信号吗？它涉及到质膜吗？什么 是信号的性质吗？这一调节电路是否与 或者与其他已知的调控回路相交？有哪些元素 核糖体RNA和核糖体蛋白基因识别信号？什么 其他基因是通过相同的途径进行调控的吗？我们将寻找 这种调节电路有缺陷的突变细胞，目的是 识别电路的组件。此外，研究还将 继续研究DNA结合蛋白Reb1p的性质，即 参与核糖体RNA的转录，并可能参与其 监管。 因为生长依赖于蛋白质合成，而蛋白质合成依赖于 在核糖体合成方面，核糖体合成的控制导致了 真正意义上的，对增长的控制。细胞生长不平衡 是导致许多疾病的原因。我们的希望和期望是， 了解核糖体调节的基础电路 当失衡时，综合将导致更有效的干预 发生。

A fundamental challenge of biology is to understand the integrated operations of a cell, that lead it to double precisely, all its components during a single generation. Our studies of the biosynthesis of ribosomes in the yeast Saccharomyces cerevisiae have led to the unexpected finding that the emphasis of ribosomes is dependent on the continued synthesis of the cell's membranes. Our view is that this represents an example of the regulatory circuits between different macromolecular components of the cells, circuits that must be present to ensure balanced growth, but that have been generally unrecognized. This process of ribosome synthesis requires the coordinated synthesis of rRNA from greater than 100 genes, and of ribosomal proteins from more than 75 genes. The study of its regulation has led to profound biological insights. This proposal will combine genetic and biochemical techniques to explore the regulatory circuit between membrane synthesis and ribosome synthesis by asking: How does a defect in membrane synthesis generate a signal? Does it involve the plasma membrane? What is the nature of the signal? Does this regulatory circuit coincide with or intersect with other known regulatory circuits? What elements of ribosomal RNA and ribosomal protein genes recognize the signal? What other genes are regulated via the same pathway? We will search for mutant cells in which this regulatory circuit is defective, with the aim of identifying components of the circuit. In addition, studies will continue on the properties of a DNA binding protein, Reb1p, that is involved in the transcription of ribosomal RNA and probably in its regulation. Since growth depends on protein synthesis, and protein synthesis depends on ribosome synthesis, the control of ribosome synthesis leads, in a very real sense, to the control of growth. Imbalance in the growth of cells is a cause of much disease. Our hope, and expectation, is that understanding the circuits that underlie the regulation of ribosome synthesis will lead to more effective intervention when an imbalance occurs.