mRNA翻译的最佳下调
Optimal Down Regulation of mRNA Translation
摘要：
mRNA翻译的下调是从开发用于肿瘤和病毒性疾病的有效药物到开发可用于疫苗接种的减毒病毒株的各种生物医学领域中的重要问题。在这里，我们研究的问题，下调mRNA翻译使用一个数学模型称为核糖体流动模型（RFM）。在RFM中，mRNA分子被建模为$n$位点的链。核糖体在连续位点之间的流动受$n+1$转换速率的调节。给定一组可行的转换率，模型的结果，所有可能的突变，我们考虑的问题，最大限度地下调翻译率通过改变这组可行的速率内的速率。在可行集上的一定条件下，我们证明了一个最优解可以有效地确定。我们还严格分析了下调优化问题的两种特殊情况。我们的研究结果表明，人们必须关注的位置沿mRNA分子的转换率有最强的影响蛋白质的生产率。然而，这个速率不一定是mRNA分子上最慢的跃迁速率。我们讨论了这些结果的生物学意义。
英文摘要：
Down regulation of mRNA translation is an important problem in various bio-medical domains ranging from developing effective medicines for tumors and for viral diseases to developing attenuated virus strains that can be used for vaccination. Here, we study the problem of down regulation of mRNA translation using a mathematical model called the ribosome flow model (RFM). In the RFM, the mRNA molecule is modeled as a chain of $n$ sites. The flow of ribosomes between consecutive sites is regulated by $n+1$ transition rates. Given a set of feasible transition rates, that models the outcome of all possible mutations, we consider the problem of maximally down regulating the translation rate by altering the rates within this set of feasible rates. Under certain conditions on the feasible set, we show that an optimal solution can be determined efficiently. We also rigorously analyze two special cases of the down regulation optimization problem. Our results suggest that one must focus on the position along the mRNA molecule where the transition rate has the strongest effect on the protein production rate. However, this rate is not necessarily the slowest transition rate along the mRNA molecule. We discuss some of the biological implications of these results.
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