An integrated approach reveals regulatory controls on bacterial translation elongation.
An integrated approach reveals regulatory controls on bacterial translation elongation.
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DOI：
10.1016/j.cell.2014.10.043
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发表时间：
2014-11-20
期刊：
影响因子：
64.5
通讯作者：
O'Shea EK
中科院分区：
文献类型：
--
作者：
Subramaniam AR;Zid BM;O'Shea EK
核糖体在翻译过程中以不均匀的速度伸长。理论模型和实验在体内延伸率的决定因素和延伸率影响蛋白质水平的机制上存在分歧。为了解决这一冲突，我们测量了多种条件下转录组范围的核糖体占有率，并用它来建立一个在大肠杆菌中翻译的全细胞模型。我们的模型预测，在营养丰富的生长过程中，大多数密码子的延伸率不受细胞内氨基酰tRNAs浓度的限制。然而，单一氨基酸在饥饿过程中的伸长暂停对tRNA氨酰化动力学高度敏感。我们进一步表明，暂停时的翻译流产解释了观察到的饥饿期间核糖体沿着mRNAs的占据。堕胎减少了全球蛋白质的合成，但它增强了mRNAs子集的翻译。这些结果表明，在应激过程中，氨基酰化和流产具有调节作用，我们的研究为模拟翻译提供了一个实验受限的框架。
Ribosomes elongate at a non-uniform rate during translation. Theoretical models and experiments disagree on the in vivo determinants of elongation rate and the mechanism by which elongation rate affects protein levels. To resolve this conflict, we measured transcriptome-wide ribosome occupancy under multiple conditions and used it to formulate a whole-cell model of translation in E. coli. Our model predicts that elongation rates at most codons during nutrient-rich growth are not limited by the intracellular concentrations of aminoacyl-tRNAs. However, elongation pausing during starvation for single amino acids is highly sensitive to the kinetics of tRNA aminoacylation. We further show that translation abortion upon pausing accounts for the observed ribosome occupancy along mRNAs during starvation. Abortion reduces global protein synthesis, but it enhances the translation of a subset of mRNAs. These results suggest a regulatory role for aminoacylation and abortion during stress, and our study provides an experimentally-constrained framework for modeling translation.
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