The Key Parameters that Govern Translation Efficiency

Abstract

Translation of mRNA into protein is a fundamental yet complex biological process with multiple factors that can potentially affect its efficiency. Here, we study a stochastic model describing the traffic flow of ribosomes along the mRNA and identify the key parameters that govern the overall rate of protein synthesis, sensitivity to initiation rate changes, and efficiency of ribosome usage. By analyzing a continuum limit of the model, we obtain closed-form expressions for stationary currents and ribosomal densities, which agree well with Monte Carlo simulations. Furthermore, we completely characterize the phase transitions in the system, and by applying our theoretical results, we formulate design principles that detail how to tune the key parameters we identified to optimize translation efficiency. Using ribosome profiling data from S. cerevisiae, we show that its translation system is generally consistent with these principles. Our theoretical results have implications for evolutionary biology, as well as for synthetic biology.

Keywords: 5′ ramp; TASEP; codon adaptation; design principles; elongation rates; hydrodynamic limit; phase diagram; ribosomal traffic jams; ribosome profiling; translation efficiency.