A chemical kinetic basis for measuring translation initiation and elongation rates from ribosome profiling data
A chemical kinetic basis for measuring translation initiation and elongation rates from ribosome profiling data
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DOI：
10.1371/journal.pcbi.1007070
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发表时间：
2018-12
影响因子：
4.3
通讯作者：
Ajeet K. Sharma;Pietro Sormanni;Nabeel Ahmed;P. Ciryam;Ulrike A. Friedrich;G. Kramer;E. O’Brien
中科院分区：
文献类型：
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作者：
Ajeet K. Sharma;Pietro Sormanni;Nabeel Ahmed;P. Ciryam;Ulrike A. Friedrich;G. Kramer;E. O’Brien
之前已经开发了基于模拟和优化的分析方法来估计下一代测序数据的相对翻译率。翻译涉及分子和化学反应；因此，符合化学和物理定律的生物信息学方法更有可能产生准确的结果。在这里，我们根据化学动力学原理推导出简单的方程，以测量核糖体分析实验中的翻译起始率、转录组范围的延伸率和单个密码子翻译率。我们的方法从详细的翻译模拟生成的核糖体图谱中再现了已知的速率。将我们的方法应用于来自酿酒酵母和小鼠胚胎干细胞的数据，我们发现提取的速率再现了与各种分子特性的预期相关性。密码子的翻译率可表现出高达 26 倍的变异性，具体取决于其在转录本中的上下文。这种广泛的分布意味着密码子的平均翻译速率不能代表该密码子的大多数实例的翻译速率。我们还发现小鼠胚胎干细胞的整体翻译速度为 5.2 AA/s，与之前使用另一种分析方法报道的相似。翻译率的这种巨大变化表明细胞对翻译调控的利用程度可能比之前想象的更大。
Analysis methods based on simulations and optimization have been previously developed to estimate relative translation rates from next-generation sequencing data. Translation involves molecules and chemical reactions; hence, bioinformatics methods consistent with the laws of chemistry and physics are more likely to produce accurate results. Here, we derive simple equations based on chemical kinetic principles to measure the translation-initiation rate, transcriptome-wide elongation rate, and individual codon translation rates from ribosome profiling experiments. Our methods reproduce the known rates from ribosome profiles generated from detailed simulations of translation. Applying our methods to data from S. cerevisiae and mouse embryonic stem cells we find that the extracted rates reproduce expected correlations with various molecular properties. A codon can exhibit up to 26-fold variability in its translation rate depending upon its context within a transcript. This broad distribution means that the average translation rate of a codon is not representative of the rate at which most instances of that codon are translated. We also find that mouse embryonic stem cells have a global translation speed of 5.2 AA/s, is similar to what has been previous reported using another analysis method. This large variability in translation rates suggests that translational regulation might be used by cells to a greater degree than previously thought.