Deciphering mRNA Sequence Determinants of Protein Production Rate

Juraj Szavits-Nossan, Luca Ciandrini, M. Carmen Romano

Research output: Contribution to journalArticle

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Abstract

One of the greatest challenges in biophysical models of translation is to identify coding sequence 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, which is the ribosome footprint length on the mRNA, together with the value of the initiation rate, are the main determinants of protein production rate under physiological conditions. Finally, we interpret the obtained analytic results based on the evolutionary role of the codons’ choice for regulating translation rates and ribosome densities.
Original languageEnglish
Article number128101
JournalPhysical Review Letters
Volume120
Issue number12
Early online date19 Mar 2018
DOIs
Publication statusPublished - 23 Mar 2018

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