title: Ribosome recycling induces optimal translation rate at low ribosomal availability.
abstract: During eukaryotic cellular protein synthesis, ribosomal translation is made more efficient through interaction between the two ends of the messenger RNA (mRNA). Ribosomes reaching the 3' end of the mRNA can thus recycle and begin translation again on the same mRNA, the so-called 'closed-loop' model. Using a driven diffusion lattice model of translation, we study the effects of ribosome recycling on the dynamics of ribosome flow and density on the mRNA. We show that ribosome recycling induces a substantial increase in ribosome current. Furthermore, for sufficiently large values of the recycling rate, the lattice does not transition directly from low to high ribosome density, as seen in lattice models without recycling. Instead, a maximal current phase becomes accessible for much lower values of the initiation rate, and multiple phase transitions occur over a wide region of the phase plane. Crucially, we show that in the presence of ribosome recycling, mRNAs can exhibit a peak in protein production at low values of the initiation rate, beyond which translation rate decreases. This has important implications for translation of certain mRNAs, suggesting that there is an optimal concentration of ribosomes at which protein synthesis is maximal, and beyond which translational efficiency is impaired.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK SUPA, Institute for Complex Systems and Mathematical Biology, King's College, University of Aberdeen, Aberdeen AB24 3UE, UK emarshall@abdn.ac.uk.
authors.forename: E
authors.initials: E
authors.lastname: Marshall
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: I
authors.initials: I
authors.lastname: Stansfield
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK SUPA, Institute for Complex Systems and Mathematical Biology, King's College, University of Aberdeen, Aberdeen AB24 3UE, UK m.romano@abdn.ac.uk.
authors.forename: M C
authors.initials: MC
authors.lastname: Romano
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004058:Diffusion; D008962:Models, Theoretical; D009154:Mutation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000502:physiology*
chemical_list: D012333:RNA, Messenger
keywords: ABCE1; Rli1; ribosome recycling; totally asymmetric simple exclusion process; translation