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

J Mol Biol. 2016 May 22;428(10 Pt B):2217-27. doi: 10.1016/j.jmb.2016.04.019. Epub 2016 Apr 21.

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.

Keywords: arrest peptides; metabolite sensing; nascent chain-mediated translational arrest; ribosome; translational control.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gene Expression Regulation, Bacterial*
  • Models, Biological
  • Peptide Biosynthesis*
  • Protein Biosynthesis / drug effects*
  • Ribosomes / chemistry
  • Ribosomes / drug effects*
  • Ribosomes / metabolism*