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

TL;DR

This paper presents a model explaining how amino acid starvation affects protein production and tRNA charging, revealing a natural community-level control mechanism in gene regulation that can increase production of certain proteins.

Contribution

It introduces a novel translation model incorporating tRNA dynamics and community resource effects, explaining unexpected protein production increases during starvation.

Findings

Starvation can increase production of some proteins.

Selective use of rare codons enables natural control.

tRNA charging dynamics explain observed effects.

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.