Translational cross talk in gene networks.
Translational cross talk in gene networks.
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DOI：
10.1016/j.bpj.2013.04.049
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发表时间：
2013-06
影响因子：
3.4
通讯作者：
W. Mather;J. Hasty;L. Tsimring;Ruth J. Williams
中科院分区：
文献类型：
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作者：
W. Mather;J. Hasty;L. Tsimring;Ruth J. Williams
实验表明，上游 mRNA 对有限翻译资源的竞争可能导致蛋白质计数之间的反相关。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物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中的概念来描述随着系统从负载不足（核糖体数量超过转录本）到过载（转录本数量超过核糖体数量）的转变，蛋白质计数统计的质变。简化随机模型的精确解析解（其中竞争 mRNA 和核糖体的数量是固定的）当总转录本计数略超过核糖体计数时，稳态蛋白质计数之间表现出弱正相关性，而当总转录本计数显着超过核糖体计数时，该解可以表现出强负相关性。扩展此分析，我们找到了更现实模型的近似但相当准确的解决方案，其中允许 mRNA 和核糖体的丰度随机波动。在这里，核糖体波动对相关性有正向贡献，而 mRNA 波动对相关性有负向贡献，并且当 mRNA 波动主导核糖体波动时，在从欠载状态到过载状态的过渡附近可靠地出现强反相关极值。
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.