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首页> 外文期刊>DNA research: an international journal for rapid publication of reports on genes and genomes >Genome scale analysis of Escherichia coli with a comprehensive prokaryotic sequence-based biophysical model of translation initiation and elongation
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Genome scale analysis of Escherichia coli with a comprehensive prokaryotic sequence-based biophysical model of translation initiation and elongation

机译：大肠杆菌基因组规模分析与综合原核序列的综合翻译和伸长率的生物物理模型

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摘要

Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribosome binding site with the ribosomal RNA. The elongation rate is affected, among other factors, by the local biophysical properties of the coding regions, the decoding rates of different codons, and the interactions among ribosomes. Currently, there is no comprehensive biophysical model of translation that enables the prediction of mRNA translation dynamics based only on the transcript sequence and while considering all of these fundamental aspects of translation. In this study, we provide, for the first time, a computational simulative biophysical model of both translation initiation and elongation with all aspects mentioned above. We demonstrate our model performance and advantages focusing on Escherichia coli genes. We further show that the model enables prediction of translation rate, protein levels, and ribosome densities. In addition, our model enables quantifying the effect of silent mutations on translation rate in different parts of the transcript, the relative effect of mutations on translation initiation and elongation, and the effect of mutations on ribosome traffic jams. Thus, unlike previous models, the proposed one provides comprehensive information, facilitating future research in disciplines such as molecular evolution, synthetic biology, and functional genomics. A toolkit to estimate translation dynamics of transcripts is available at: https://www.cs.tau.ac.il/similar to tamirtul/transim
机译：原核生物中的翻译引发受核糖体RNA核糖体结合位点的mRNA折叠和相互作用的影响。在其他因素中，伸长率受到编码区的局部生物物理性质，不同密码子的解码率和核糖体之间的相互作用的影响。目前，没有全面的翻译模型，使得仅在考虑到的转录序列上预测MRNA翻译动态，同时考虑到所有这些基本方面的翻译方面。在这项研究中，我们首次提供翻译启动和伸长率的计算模拟生物物理模型与上述所有方面。我们展示了专注于大肠杆菌基因的模型性能和优势。我们进一步表明该模型能够预测翻译率，蛋白质水平和核糖体密度。此外，我们的模型使得能够量化沉默突变在转录物的不同部分中的翻译速率的影响，突变对翻译引发和伸长的相对效果，以及突变对核糖体交通堵塞的影响。因此，与以前的模型不同，建议提供了全面的信息，促进了未来的学科研究，如分子演化，合成生物学和功能基因组学。用于估算转换转换动态的工具包可用于：https://www.cs.tau.ac.il/imilar到Tamirtul / Transim

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