Deciphering mRNA Sequence Determinants of Protein Production Rate

Abstract

One of the greatest challenges in biophysical models of translation is to identify coding sequences features that affect the rate of translation and therefore the overall protein production in the cell. We propose an analytic method to solve a translation model based on the inhomogeneous totally asymmetric simple exclusion process, which allows us to unveil simple design principles of nucleotide sequences determining protein production rates. Our solution shows an excellent agreement when compared to numerical genome-wide simulations of S. cerevisiae transcript sequences and predicts that the first 10 codons, together with the value of the initiation rate, are the main determinants of protein production rate. Finally, we interpret the obtained analytic results based on the evolutionary role of codons' choice for regulating translation rates and ribosome densities.

6 pages, 3 figures, Supplemental Material (4 pages)

References in corpus (3)

• Nonequilibrium Steady States of Matrix Product Form: A Solver's Guide
• Effects of the chemomechanical stepping cycle on the traffic of molecular motors
• Defect-induced phase transition in the asymmetric simple exclusion process

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• Totally asymmetric exclusion process with site-wise dynamic disorder
• Power series solution of the inhomogeneous exclusion process
• Driven transport on a flexible polymer with particle recycling: a model inspired by transcription and translation
• Power series method for solving TASEP-based models of mRNA translation
• Dynamics of ribosomes in mRNA translation under steady and non-steady state conditions
• Current-density relation in the exclusion process with dynamic obstacles
• Matrix product solution for a partially asymmetric 1D lattice gas with a free defect
• Integrability of two-species partially asymmetric exclusion processes
• EGGTART: A computational tool to visualize the dynamics of biophysical transport processes under the inhomogeneous $\ell$-TASEP
• The fitness landscapes of translation
• Exclusion process subject to conformational size changes