Membrane proteins in all living organisms are inserted to the membrane during their translation. To achieve this, ribosomes translating membrane proteins are targeted to membrane translocons early in translation, by the ubiquitous Signal Recognition Particle (SRP) pathway. In Eukaryotes, the SRP arrests translation elongation of membrane proteins until targeting is complete. Curiously however, the arrest function is lacking in most eubacteria. Here we identify a compensatory mechanism in E. coli that serves to slow down translation during membrane protein targeting. By computationally analyzing genome-wide translation rates in E. coli, we find that elongation pauses are enriched during membrane protein targeting. The underlying mechanism is programmed into the coding sequence, where Shine-Dalgarno-like elements act to slow elongation at strategic positions. We provide experimental evidence that the pauses improve membrane protein quality control, as slower translation during targeting correlates with better folding of membrane proteins expressed from plasmid. Thus, slow elongation is important for membrane protein targeting not only in eukaryotes, but also in E. coli, which utilizes a mechanisms different from the eukaryotic one to slow translation.
