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 (namely, the inhomogeneous $\ell$-TASEP), 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 shows that its translation system is generally consistent with these principles. Our theoretical results have implications for evolutionary biology, as well as synthetic biology.

arXiv commentTo appear in Cell Systems. 32 pages, 10 figures, 1 table

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Cited by in corpus (13)

• Steady states and phase transitions in heterogeneous asymmetric exclusion processes
• Dynamics of ribosomes in mRNA translation under steady and non-steady state conditions
• Current-density relation in the exclusion process with dynamic obstacles
• EGGTART: A computational tool to visualize the dynamics of biophysical transport processes under the inhomogeneous $\ell$-TASEP
• Exclusion model of mRNA translation with collision-induced ribosome drop-off
• Role of interactions in a closed quenched system
• Density- and elongation speed-dependent error correction in RNA polymerization
• The fitness landscapes of translation
• Polysomally Protected Viruses
• Single-file transport of binary hard-sphere mixtures through periodic potentials
• Weak pinning and long-range anticorrelated motion of phase boundaries in driven diffusive systems
• Correlations of density and current fluctuations in single-file motion of hard spheres and in driven lattice gas with nearest-neighbor interaction
• Nonequilibrium phase transition in single-file transport at high crowding