Genome scale analysis of Escherichia coli with a comprehensive prokaryotic sequence-based biophysical model of translation initiation and elongation.

Abstract

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/∼tamirtul/transim