Castellana Michele, Hsin-Jung Li Sophia, Wingreen Ned S
Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ 08544; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544; Laboratoire Physico-Chimie Curie, Institut Curie, CNRS UMR168, 75005 Paris, France;
Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):9286-91. doi: 10.1073/pnas.1604995113. Epub 2016 Aug 2.
In bacteria such as Escherichia coli, DNA is compacted into a nucleoid near the cell center, whereas ribosomes-molecular complexes that translate mRNAs into proteins-are mainly localized to the poles. We study the impact of this spatial organization using a minimal reaction-diffusion model for the cellular transcriptional-translational machinery. Although genome-wide mRNA-nucleoid segregation still lacks experimental validation, our model predicts that [Formula: see text] of mRNAs are segregated to the poles. In addition, our analysis reveals a "circulation" of ribosomes driven by the flux of mRNAs, from synthesis in the nucleoid to degradation at the poles. We show that our results are robust with respect to multiple, biologically relevant factors, such as mRNA degradation by RNase enzymes, different phases of the cell division cycle and growth rates, and the existence of nonspecific, transient interactions between ribosomes and mRNAs. Finally, we confirm that the observed nucleoid size stems from a balance between the forces that the chromosome and mRNAs exert on each other. This suggests a potential global feedback circuit in which gene expression feeds back on itself via nucleoid compaction.
在诸如大肠杆菌这样的细菌中,DNA被压缩成靠近细胞中心的类核,而核糖体(将mRNA翻译成蛋白质的分子复合物)主要定位于细胞两极。我们使用一个用于细胞转录 - 翻译机制的最小反应 - 扩散模型来研究这种空间组织的影响。尽管全基因组范围内的mRNA - 类核分离仍缺乏实验验证,但我们的模型预测约[公式:见原文]的mRNA被分离到细胞两极。此外,我们的分析揭示了由mRNA通量驱动的核糖体“循环”,从类核中的合成到两极的降解。我们表明,我们的结果对于多种生物学相关因素具有稳健性,例如RNase酶对mRNA的降解、细胞分裂周期的不同阶段和生长速率,以及核糖体与mRNA之间非特异性、瞬时相互作用的存在。最后,我们证实观察到的类核大小源于染色体和mRNA相互施加的力之间的平衡。这表明存在一种潜在的全局反馈回路,其中基因表达通过类核压缩对自身产生反馈。