Deciphering mRNA Sequence Determinants of Protein Production Rate

TL;DR

This paper introduces an analytic method to identify key mRNA sequence features that influence protein production rates, revealing the importance of the first 10 codons and initiation rate in translation efficiency.

Contribution

It presents a novel analytic solution to a translation model, providing simple design principles for nucleotide sequences affecting protein synthesis rates.

Findings

First 10 codons significantly impact protein production.

Initiation rate is a major determinant of translation efficiency.

Model predictions align well with genome-wide simulations.

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.