RIBOSOMAL GENES OF YEAST AND THEIR REGULATION

生物学的一个基本挑战是理解 一个细胞的操作，这导致它精确地加倍，所有它的 在一代人的时间里。 我们对生物合成的研究 核糖体在酵母酿酒酵母导致了 出乎意料的发现是，核糖体的重点是依赖于 继续合成细胞膜。 我们认为， 图13示出了不同的控制电路之间的调节电路的示例。 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。 核糖体合成的这一过程需要协调合成 rRNA来自100多个基因，核糖体蛋白来自更多的基因。 75个基因 对其调节的研究导致了深刻的 生物学见解。 这项建议将联合收割机遗传和生化 技术来探索膜合成之间的调节回路 和核糖体合成的问题： 合成产生信号？ 它涉及到质膜吗？ 什么 是信号的本质吗 这种调节电路是否与 或与其他已知的监管电路相交？ 中的哪些因素 核糖体RNA和核糖体蛋白基因识别信号？ 什么 其他基因也是通过同样的途径调控的吗 我们会寻找 突变细胞，其中该调节回路有缺陷，目的是 识别电路的组成部分。 此外，研究将 继续研究DNA结合蛋白Reb1p的性质，即 参与核糖体RNA的转录， 调控 因为生长依赖于蛋白质的合成，而蛋白质的合成依赖于 在核糖体合成上，核糖体合成的控制导致，在一个非常 真实的意义上，要控制增长。 细胞生长的不平衡 是许多疾病的原因。 我们的希望和期望是， 了解核糖体调节的基础电路 当出现不平衡情况时， 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.