Department of Physics, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Biophys J. 2013 Jun 4;104(11):2564-72. doi: 10.1016/j.bpj.2013.04.049.
It has been shown experimentally that competition for limited translational resources by upstream mRNAs can lead to an anticorrelation between protein counts. Here, we investigate a stochastic model for this phenomenon, in which gene transcripts of different types compete for a finite pool of ribosomes. Throughout, we utilize concepts from the theory of multiclass queues to describe a qualitative shift in protein count statistics as the system transitions from being underloaded (ribosomes exceed transcripts in number) to being overloaded (transcripts exceed ribosomes in number). The exact analytical solution of a simplified stochastic model, in which the numbers of competing mRNAs and ribosomes are fixed, exhibits weak positive correlations between steady-state protein counts when total transcript count slightly exceeds ribosome count, whereas the solution can exhibit strong negative correlations when total transcript count significantly exceeds ribosome count. Extending this analysis, we find approximate but reasonably accurate solutions for a more realistic model, in which abundances of mRNAs and ribosomes are allowed to fluctuate randomly. Here, ribosomal fluctuations contribute positively and mRNA fluctuations contribute negatively to correlations, and when mRNA fluctuations dominate ribosomal fluctuations, a strong anticorrelation extremum reliably occurs near the transition from the underloaded to the overloaded regime.
实验表明，上游 mRNA 对有限翻译资源的竞争会导致蛋白质数量之间呈反相关。在这里，我们研究了这种现象的随机模型，其中不同类型的基因转录本竞争有限的核糖体池。在整个过程中，我们利用多类队列理论的概念来描述蛋白质计数统计数据的定性变化，因为系统从欠载（核糖体数量超过转录本数量）过渡到过载（转录本数量超过核糖体数量）。简化随机模型的精确解析解，其中竞争的 mRNA 和核糖体数量是固定的，当总转录本计数略超过核糖体计数时，稳定状态蛋白质计数之间存在微弱的正相关，而当总转录本计数显著超过核糖体计数时，解可以显示出强烈的负相关。扩展此分析，我们为更现实的模型找到近似但相当准确的解，其中允许 mRNA 和核糖体的丰度随机波动。在这里，核糖体波动的影响是正相关，mRNA 波动的影响是负相关，当 mRNA 波动主导核糖体波动时，在从欠载到过载的过渡附近，可靠地出现强烈的反相关极值。
