Abstract

In all living organisms, ribosomes translating membrane proteins are targeted to membrane translocons early in translation, by the ubiquitous Signal Recognition Particle (SRP) system. In eukaryotes, the SRP Alu domain arrests translation elongation of membrane proteins until targeting is complete. Curiously however, the Alu domain is lacking in most eubacteria. Here, by analyzing genome-wide data on translation rates, we identified a potential compensatory mechanism in E. coli that serves to slow down translation during membrane protein targeting. The underlying mechanism is likely programmed into the coding sequence, where Shine-Dalgarno-like elements trigger elongation pauses at strategic positions during early stages of translation. We provide experimental evidence that slow translation during targeting improves membrane protein production fidelity, as it correlates with better folding of overexpressed membrane proteins. Thus, slow elongation is important for membrane protein targeting in E. coli, which utilizes mechanisms different from the eukaryotic one to control translation speed.