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

转录本丰度随细胞大小和细胞分裂的变化而变化

• 批准号: 10093078
• 负责人: BRUCE Bruce FUTCHER
• 金额: $ 31.38万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10093078
• 关键词: Achievement; Carbohydrates; Cell Cycle; Cell Size; Cell division; Cells; Characteristics; Defect; Dependence; Fission Yeast; G1 Phase; Genes; Growth; Half-Life; Homeostasis; Human; Lipids; Mammals; Measures; Messenger RNA; Modeling; Nutrient; Proteins; Salts; Testing; Transcript; Translations; Yeasts; cell growth; falls; inhibitor/antagonist; prevent; promoter; theories; transcription factor; Achievement; Carbohydrates; Cell Cycle; Cell Size; Cell division; Cells; Characteristics; Defect; Dependence; Fission Yeast; G1 Phase; Genes; Growth; Half-Life; Homeostasis; Human; Lipids; Mammals; Measures; Messenger RNA; Modeling; Nutrient; Proteins; Salts; Testing; Transcript; Translations; Yeasts; cell growth; falls; inhibitor/antagonist; prevent; promoter; theories; transcription factor

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 too small, and it co- ordinates division with the availability of nutrients and cell growth in mass. As a consequence of size control, cells have narrow and characteristic distributions of cell size. 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. We have recently discovered that as G1 phase yeast cells grow in size, several hundred mRNAs are systematically expressed at higher and higher levels—they increase faster than the increase in size, and increase in concentration. Other mRNAs do the opposite—they increase slower than the increase in size, and so decrease in concentration. 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 suggests that the ratio of activators to inhibitors increases as G1 phase cells grow, and that it is achievement of a critical ratio of many activators to inhibitors that triggers cell cycle entry. Here, we test the generality of this idea, by examining mRNA scaling-with-size in the yeast S. pombe and in human cells, and we will test two theories for the mechanism of differential-scaling-with-size. Finally we will ask if similar scaling occurs at the level of translation.

抽象的： 所有细胞都必须在承诺细胞之前生长到最小尺寸（“临界大小”） 分配。这种尺寸的需求可以防止细胞变得太大或太小，并且可以共同 将养分的可用性和质量细胞生长的可用性进行训练。由于 尺寸控制，细胞具有细胞尺寸的狭窄和特征分布。尽管数十年 研究，尚不清楚细胞如何测量和响应大小，或者为什么机械的最小值 承诺分裂需要大小。我们最近发现，作为G1阶段 酵母细胞的大小生长，在较高的情况下系统地表达了几百个mRNA，并且 较高的水平 - 它们的增加速度快于大小的增加和浓度增加。 其他mRNA相反 - 它们的增加比大小的增加慢，因此减小 集中度。令人惊讶的是，激活细胞周期的基因落入第一组，而 抑制细胞周期的基因落入第二组。这表明比率 随着G1相细胞的增长，激活剂会增加抑制剂，并且它正在实现关键 许多激活剂与触发细胞周期进入的抑制剂的比率。在这里，我们测试了 通过检查酵母菌和人类细胞中的mRNA缩放和大小的mRNA缩放，以及 我们将测试两种理论，以实现与大小的差异尺寸的机理。最后我们会问是否 类似的缩放在翻译级别也会发生。