Perspective
How Widespread is Metabolite Sensing by Ribosome-Arresting Nascent Peptides?

https://doi.org/10.1016/j.jmb.2016.04.019Get rights and content
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Highlights

  • Arrest peptides regulate gene expression in response to changing metabolite levels.

  • The range of ligands that can be sensed by arrest peptides is unknown.

  • The extent and diversity of arrest peptides in nature is not fully established.

  • Existing methods to identify new arrest peptides are limited in their scope.

  • New large-scale, high-throughput techniques are needed to push the field forward.

Abstract

In order to colonize a niche and compete for scarce resources, microorganisms have evolved means to adjust the expression levels of their biosynthetic enzymes in response to the changing levels of metabolites available to them. To do so, they often rely on transcription factors or structured RNAs that directly sense the concentration of metabolites and turn genes on or off accordingly. In some instances, however, a metabolite can be sensed by an actively translating ribosome bearing a nascent polypeptide whose specific amino acid sequence interferes with translation. These “arrest peptides” lead to the formation of stalled ribosome nascent chain complexes on the mRNA that can regulate the expression of downstream genes through transcriptional or translational mechanisms. Although this process was discovered over three and a half decades ago, the extent to which arrest peptides regulate gene expression in response to cell metabolites is unknown. Here, we examine the physical constraints imposed by the ribosome on peptide-mediated ligand sensing and review attempts to assess the diversity of arrest peptides to date. In addition, we outline a possible way forward to establish how pervasive metabolite sensing by arrest peptides is in nature.

Abbreviations

RNC
ribosome-nascent chain complexes
iNP
integrated in vivo/vitro nascent chain profiling

Keywords

ribosome
arrest peptides
nascent chain-mediated translational arrest
translational control
metabolite sensing

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