Department of Physics, Kyushu University, Motooka 744, Fukuoka, 819-0395, Japan.
Sci Rep. 2022 Jun 22;12(1):10516. doi: 10.1038/s41598-022-14719-4.
Gene expression via transcription-translation is the most fundamental reaction to sustain biological systems, and complex reactions occur in a small compartment of living cells. There is increasing evidence that physical effects, such as molecular crowding or excluded volume effects of transcriptional-translational machinery, affect the yield of reaction products. On the other hand, transcriptional feedback that controls gene expression during mRNA synthesis is also a vital mechanism that regulates protein synthesis in cells. However, the excluded volume effect of spatial constraints on feedback regulation is not well understood. Here, we study the confinement effect on transcriptional autoregulatory feedbacks of gene expression reactions using a theoretical model. The excluded volume effects between molecules and the membrane interface suppress the gene expression in a small cell-sized compartment. We find that negative feedback regulation at the transcription step mitigates this size-induced gene repression and alters the scaling relation of gene expression level on compartment volume, approaching the regular scaling relation without the steric effect. This recovery of regular size-scaling of gene expression does not appear in positive feedback regulation, suggesting that negative autoregulatory feedback is crucial for maintaining reaction products constant regardless of compartment size in heterogeneous cell populations.
通过转录-翻译进行基因表达是维持生物系统的最基本反应，而复杂的反应发生在活细胞的小隔室中。越来越多的证据表明，物理效应，如转录-翻译机器的分子拥挤或排除体积效应，会影响反应产物的产量。另一方面，控制 mRNA 合成过程中基因表达的转录反馈也是调节细胞中蛋白质合成的重要机制。然而，空间限制对反馈调节的排除体积效应还不太清楚。在这里，我们使用理论模型研究了基因表达反应的转录自动反馈的限制效应。分子和膜界面之间的排除体积效应会抑制小细胞大小隔室中的基因表达。我们发现，转录步骤中的负反馈调节减轻了这种大小诱导的基因抑制作用，并改变了基因表达水平对隔室体积的缩放关系，接近没有空间效应的规则缩放关系。这种基因表达的规则尺寸缩放的恢复在正反馈调节中并不明显，这表明负自动反馈对于维持无论在异质细胞群体中隔室大小如何，反应产物的恒定是至关重要的。
