@article {bhattacharyya2018accessibility, title = {Accessibility of the Shine-Dalgarno sequence dictates N-terminal codon bias in E. coli}, journal = {Molecular cell}, volume = {70}, year = {2018}, pages = {894{\textendash}905}, publisher = {Elsevier}, abstract = {Despite considerable efforts, no physical mechanism has been shown to explain\ N-terminalcodon bias\ in\ prokaryotic\ genomes. Using a systematic study of\ synonymous substitutions\ in two endogenous\ E.\ coli\ genes, we show that interactions between the\ coding region\ and the upstream\ Shine-Dalgarno\ (SD) sequence modulate the efficiency of translation initiation, affecting both intracellular mRNA and protein levels due to the inherent coupling of\ transcription\ and translation in\ E.\ coli. We further demonstrate that far-downstream mutations can also modulate mRNA levels by occluding the SD sequence through the formation of non-equilibrium secondary structures. By contrast, a non-endogenous\ RNA polymerase\ that decouples transcription and translation largely alleviates the effects of synonymous substitutions on mRNA levels. Finally, a complementary statistical analysis of the\ E.\ coli\ genome specifically implicates avoidance of intra-molecular base pairing with the SD sequence. Our results provide general physical insights into the coding-level features that optimize\ protein expression\ in prokaryotes.}, url = {https://www.sciencedirect.com/science/article/pii/S1097276518303587}, author = {Bhattacharyya, Sanchari and Jacobs, William M and Adkar, Bharat V and Jin Yan and Zhang, Wenli and Shakhnovich, EugeneI.} }