Community control in cellular protein production: Consequences for amino acid starvation

Frank S. Heldt, Chris A. Brackley, Celso Grebogi, Marco Thiel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 herewe 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 amodel 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.

Original languageEnglish
Article number20150107
JournalPhilosophical Transactions A: Mathematical, Physical and Engineering Sciences
Volume373
Issue number2056
DOIs
Publication statusPublished - 13 Dec 2015

Keywords

  • Amino acid starvation
  • Gene regulation
  • mRNA translation

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