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About the Authors:
David W. Rogers
Contributed equally to this work with: David W. Rogers, Marvin A. Böttcher
* E-mail: [email protected]
Affiliations Experimental Evolution Research Group, Max Planck Institute for Evolutionary Biology, Plön, Germany, Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany
ORCID http://orcid.org/0000-0002-1431-2676
Marvin A. Böttcher
Contributed equally to this work with: David W. Rogers, Marvin A. Böttcher
Affiliation: Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany
ORCID http://orcid.org/0000-0003-3992-5273
Arne Traulsen
Affiliation: Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany
Duncan Greig
Affiliations Experimental Evolution Research Group, Max Planck Institute for Evolutionary Biology, Plön, Germany, Department of Genetics, Evolution, and Environment, University College London, London, United KingdomAbstract
Models of mRNA translation usually presume that transcripts are linear; upon reaching the end of a transcript each terminating ribosome returns to the cytoplasmic pool before initiating anew on a different transcript. A consequence of linear models is that faster translation of a given mRNA is unlikely to generate more of the encoded protein, particularly at low ribosome availability. Recent evidence indicates that eukaryotic mRNAs are circularized, potentially allowing terminating ribosomes to preferentially reinitiate on the same transcript. Here we model the effect of ribosome reinitiation on translation and show that, at high levels of reinitiation, protein synthesis rates are dominated by the time required to translate a given transcript. Our model provides a simple mechanistic explanation for many previously enigmatic features of eukaryotic translation, including the negative correlation of both ribosome densities and protein abundance on transcript length, the importance of codon usage in determining protein synthesis rates, and the negative correlation between transcript length and both codon adaptation and 5' mRNA folding energies. In contrast to linear models where translation is largely limited by initiation rates, our model reveals that all three stages of translation-initiation, elongation, and termination/reinitiation-determine protein synthesis rates even at low ribosome availability.
Author summary
Recent advances in proteomics show that translation is strongly dependent on transcript length, but current theoretical models fail to capture this relationship. Here, we propose that the high initiation rates and protein yields of short transcripts result from terminating ribosomes reinitiating on the same transcript. The frequency of reinitiation depends on the time required to...