How Widespread is Metabolite Sensing by Ribosome-Arresting Nascent Peptides?
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.
University of Bordeaux, Institut Européen de Chimie et Biologie, 33607 Pessac, France; Institut National de la Santé et de la Recherche Médicale, Inserm U1212, 33076 Bordeaux, France; Centre National de la Recherche Scientifique, CNRS UMR 5320, 33076 Bordeaux, France.
Britta
B
Seip
University of Bordeaux, Institut Européen de Chimie et Biologie, 33607 Pessac, France; Institut National de la Santé et de la Recherche Médicale, Inserm U1212, 33076 Bordeaux, France; Centre National de la Recherche Scientifique, CNRS UMR 5320, 33076 Bordeaux, France. Electronic address: axel.innis@inserm.fr.
C Axel
CA
Innis
D015964:Gene Expression Regulation, Bacterial; D008954:Models, Biological; D010452:Peptide Biosynthesis; D014176:Protein Biosynthesis / Q000187:drug effects*; D012270:Ribosomes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*
arrest peptides; metabolite sensing; nascent chain-mediated translational arrest; ribosome; translational control