How do bacteria tune translation efficiency?

•The rates of protein production are precisely tuned in bacteria to meet cellular demand.•The general strategy to quantitatively modulate translation efficiency (TE) is not well understood.•High-throughput methods provide new approach to study TE for endogenous and synthetic genes.•A theoretical framework is provided for interpreting these measurements of TE.

Bacterial proteins are translated with precisely determined rates to meet cellular demand. In contrast, efforts to express recombinant proteins in bacteria are often met with large unpredictability in their levels of translation. The disconnect between translation of natural and synthetic mRNA stems from the lack of understanding of the strategy used by bacteria to tune translation efficiency (TE). The development of array-based oligonucleotide synthesis and ribosome profiling provides new approaches to address this issue. Although the major determinant for TE is still unknown, these high-throughput studies point out a statistically significant but mild contribution from the mRNA secondary structure around the start codon. Here I summarize those findings and provide a theoretical framework for measuring TE.