How do bacteria tune translation efficiency?

Abstract

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.

Figure 1

Defining translation efficiency and other kinetic constants in gene expression. The mRNA (M) is transcribed from DNA at a rate k₁ and degraded (ϕ) with a rate constant λ₁. The corresponding protein (P) is translated from mRNA with a rate constant k₂ and degraded (ϕ) with a rate constant λ₂. Translation efficiency is defined as k₂ in this Review. See Box 1.

Figure 2

Calculation of ribosome density. Consider a molecule of mRNA of length N (cylinder). The transition rate constant from position i to i+1 is r_i. The ribosome occupancy at position i is q_i. Assuming that every ribosome that initiates on the mRNA finishes translation, the steady state condition requires that the rate of producing a full-length protein from this mRNA (k₂) is the same as the rate of initiation. See Box 2.