Genome-Scale Biology Research Program, Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
G3 (Bethesda). 2013 Jan;3(1):75-90. doi: 10.1534/g3.112.004283. Epub 2013 Jan 1.
In this work, we map the transcriptional targets of 107 previously identified Drosophila genes whose loss caused the strongest cell-cycle phenotypes in a genome-wide RNA interference screen and mine the resulting data computationally. Besides confirming existing knowledge, the analysis revealed several regulatory systems, among which were two highly-specific and interconnected feedback circuits, one between the ribosome and the proteasome that controls overall protein homeostasis, and the other between the ribosome and Myc/Max that regulates the protein synthesis capacity of cells. We also identified a set of genes that alter the timing of mitosis without affecting gene expression, indicating that the cyclic transcriptional program that produces the components required for cell division can be partially uncoupled from the cell division process itself. These genes all have a function in a pathway that regulates the phosphorylation state of Cdk1. We provide evidence showing that this pathway is involved in regulation of cell size, indicating that a Cdk1-regulated cell size checkpoint exists in metazoans.
在这项工作中，我们绘制了 107 个先前确定的果蝇基因的转录靶标图谱，这些基因的缺失在全基因组 RNA 干扰筛选中导致了最强的细胞周期表型，并对由此产生的数据进行了计算机挖掘。除了证实现有的知识外，该分析还揭示了几个调控系统，其中包括两个高度特异性和相互关联的反馈回路，一个是核糖体和蛋白酶体之间的回路，控制着整体蛋白质稳态，另一个是核糖体和 Myc/Max 之间的回路，调节细胞的蛋白质合成能力。我们还鉴定了一组改变有丝分裂时间而不影响基因表达的基因，表明产生细胞分裂所需成分的周期性转录程序可以部分与细胞分裂过程本身脱耦。这些基因在调节 Cdk1 磷酸化状态的途径中都有一个功能。我们提供的证据表明，该途径参与了细胞大小的调节，表明在后生动物中存在 Cdk1 调节的细胞大小检查点。
