Protein synthesis rates are determined, at the translational level, by properties of the transcript's sequence. The efficiency of an mRNA can be tuned by varying the ribosome binding sites controlling the recruitment of the ribosomes, or the codon usage establishing the speed of protein elongation. In this work we propose transcript length as a further key determinant of translation efficiency. Based on a physical model that considers the kinetics of ribosomes advancing on the mRNA and diffusing in its surrounding, as well as mRNA circularisation and ribosome drop-off, we explain how the transcript length may play a central role in establishing ribosome recruitment and the overall translation rate of an mRNA. According to our results, the proximity of the 3′ end to the ribosomal recruitment site of the mRNA could induce a feedback in the translation process that would favour the recycling of ribosomes. We also demonstrate how this process may be involved in shaping the experimental ribosome density-gene length dependence. Finally, we argue that cells could exploit this mechanism to adjust and balance the usage of its ribosomal resources.
Bibliographical noteThe authors would like to acknowledge the funding provided by the European Union Seventh Framework Programme [FP7/2007–2013] (NICHE; grant agreement 289384) (LDF). LDF also acknowledges the funding provided by the São Paulo Research Foundation (FAPESP - grant #2015/26989-4). AM was partially funded by the UK Biotechnology and Biological Research Council (BBSRC), through grant BB/N015711/1. LC would like to acknowledge Maria Carmen Romano, Jean Hausser, Marco Cosentino Lagomarsino, Jean-Charles Walter and Norbert Kern for early discussions on this work, and the CNRS for having granted him a “demi-délégation” (2017–18). We would like to dedicate this work in memory of Maxime Clusel and Vladimir Lorman.
- biological physics
- systems biology