title: Community control in cellular protein production: consequences for amino acid starvation.
abstract: Deprivation of essential nutrients can have stark consequences for many processes in a cell. We consider amino acid starvation, which can result in bottlenecks in mRNA translation when ribosomes stall due to lack of resources, i.e. tRNAs charged with the missing amino acid. Recent experiments also show less obvious effects such as increased charging of other (non-starved) tRNA species and selective charging of isoaccepting tRNAs. We present a mechanism which accounts for these observations and shows that production of some proteins can actually increase under starvation. One might assume that such responses could only be a result of sophisticated control pathways, but here we show that these effects can occur naturally due to changes in the supply and demand for different resources, and that control can be accomplished through selective use of rare codons. We develop a model for translation which includes the dynamics of the charging and use of aminoacylated tRNAs, explicitly taking into account the effect of specific codon sequences. This constitutes a new control mechanism in gene regulation which emerges at the community level, i.e. via resources used by all ribosomes.
authors.affiliation: Otto von Guericke University Magdeburg, Universitaetsplatz 2, 39106 Magdeburg, Germany.
authors.forename: Frank S
authors.identifier: http://orcid.org/0000-0002-9276-5013
authors.initials: FS
authors.lastname: Heldt
authors.affiliation: SUPA, School of Physics and Astronomy, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JZ, UK.
authors.forename: Chris A
authors.identifier: http://orcid.org/0000-0002-5973-8179
authors.initials: CA
authors.lastname: Brackley
authors.affiliation: Institute for Complex Systems and Mathematical Biology, SUPA, King's College, University of Aberdeen, Aberdeen AB24 3UE, UK.
authors.forename: Celso
authors.initials: C
authors.lastname: Grebogi
authors.affiliation: Institute for Complex Systems and Mathematical Biology, SUPA, King's College, University of Aberdeen, Aberdeen AB24 3UE, UK m.thiel@abdn.ac.uk.
authors.forename: Marco
authors.initials: M
authors.lastname: Thiel
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D049148:Aminoacylation; D003062:Codon; D003198:Computer Simulation; D005786:Gene Expression Regulation; D007700:Kinetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry*; D012343:RNA, Transfer / Q000737:chemistry*; D012270:Ribosomes / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D003062:Codon; D011506:Proteins; D012343:RNA, Transfer
keywords: amino acid starvation; gene regulation; mRNA translation