Scaling of transcript abundance with cell size and the commitment to cell division

项目摘要/摘要 在提交给单元之前，所有单元必须增长到最小大小--“临界大小” 组织。此大小要求防止单元格变得太大或太小，并协调 随着细胞的大量生长而分裂。作为大小控制的结果，单元格具有狭窄和 细胞大小的特征分布--即大小动态平衡。尽管经过了几十年的研究，但它是 不知道细胞如何测量和响应大小，或者为什么机械地说最小大小是 对组织的承诺是必需的。这项资助的第一个期限表明，随着酵母细胞的生长 在大小上，成百上千的mRNA在越来越高的水平系统地表达-它们 丰度的增加快于细胞大小的增加，因此它们的浓度也增加了。 这就是所谓的“超比例”。其他的mRNA则相反--它们的增长速度慢于 规模的增加和浓度的减少--称为“分尺度”。令人惊讶的是， 激活细胞周期属于第一类，而抑制细胞周期的基因属于 第二组。这立即提出了一个细胞大小控制的“比例”模型 动态平衡：随着G1期细胞的生长，激活剂和抑制物的比例增加，并在 足够高浓度的激活剂、抑制剂被克服，细胞致力于 组织。控制单元格大小的“大小定标器”是产生不同比例的 基因表达。在这里，这一想法的关键方面将得到检验。将开发一个系统，用于 准确测量基因表达的比例。将开发一套系统，以准确地 测量承诺分裂时细胞大小的变化。最重要的是，这些新的- 开发的测试将被用来检验几种关于基因被激活的机制的假说。 与大小不同地表达。我们将讨论“比例”模型的一般性。 最后，将考虑在翻译层面上也发生伸缩的可能性。

Project Summary/Abstract All cells must grow to a minimum size—the “critical size”—before they can commit to cell division. This size requirement prevents cells from becoming too big or small, and co-ordinates division with cell growth in mass. As a consequence of size control, cells have narrow and characteristic distributions of cell size—that is, size homeostasis. Despite decades of study, it is unknown how cells measure and respond to size, or why mechanistically a minimum size is required for commitment to division. The first term of this grant showed that as yeast cells grow in size, hundreds of mRNAs are systematically expressed at higher and higher levels—they increase in abundance faster than the increase in cell size, and so they increase in concentration. This is termed “super-scaling”. Other mRNAs do the opposite—they increase slower than the increase in size, and decrease in concentration—termed “sub-scaling”. Strikingly, genes that activate the cell cycle fall into the first group, while genes that inhibit the cell cycle fall into the second group. This immediately suggests a “Scaling” model for cell size control and homeostasis: the ratio of activators to inhibitors increases as G1 phase cells grow, and at a sufficiently high concentration of activators, inhibitors are overcome, and cells commit to division. The “sizer” that controls cell size is the mechanism that produces differential scaling of gene expression. Here, key aspects of this idea will be tested. A system will be developed for accurately measuring scaling of gene expression. A system will be developed for accurately measuring the variation in cell size at commitment to division. Most importantly, these newly- developed assays will be used to test several hypotheses for the mechanism by which genes are differentially expressed with size. The generality of the “Scaling” model will be addressed. Finally, the possibility that scaling is also occurring at the level of translation will be considered.