Community control in cellular protein production

consequences for amino acid starvation

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

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2 Citations (Scopus)
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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 aa-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 of the Royal Society A: Mathematical, Physical & Engineering Sciences
Volume373
Issue number2056
Early online date2 Nov 2015
DOIs
Publication statusPublished - 13 Dec 2015

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ribosomes
charging
amino acids
Amino Acids
Amino acids
resources
proteins
Proteins
Protein
Resources
deprivation
Gene Regulation
gene expression
nutrients
Nutrients
Messenger RNA
Pathway
Gene expression
Cell
cells

Cite this

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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 aa-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.",
author = "Heldt, {Frank S} and Brackley, {Chris A.} and Celso Grebogi and Marco Thiel",
note = "The authors thank M. C. Romano, I. Stansfield, L. Ciandrini, A. Kort, and M. Rehberg for helpful discussions. This work was funded by BBSRC grants BB/F00513/X1 and BB/G010722, and the Scottish Universities Life Science Alliance (SULSA).",
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T2 - consequences for amino acid starvation

AU - Heldt, Frank S

AU - Brackley, Chris A.

AU - Grebogi, Celso

AU - Thiel, Marco

N1 - The authors thank M. C. Romano, I. Stansfield, L. Ciandrini, A. Kort, and M. Rehberg for helpful discussions. This work was funded by BBSRC grants BB/F00513/X1 and BB/G010722, and the Scottish Universities Life Science Alliance (SULSA).

PY - 2015/12/13

Y1 - 2015/12/13

N2 - 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 aa-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.

AB - 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 aa-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.

U2 - 10.1098/rsta.2015.0107

DO - 10.1098/rsta.2015.0107

M3 - Article

VL - 373

JO - Philosophical Transactions of the Royal Society A: Mathematical, Physical & Engineering Sciences

JF - Philosophical Transactions of the Royal Society A: Mathematical, Physical & Engineering Sciences

SN - 1364-503X

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M1 - 20150107

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