Transcriptional frameshifting rescues Citrobacter rodentium type VI secretion by the production of two length variants from the prematurely interrupted tssM gene

PLoS Genet. 2014 Dec 4;10(12):e1004869. doi: 10.1371/journal.pgen.1004869. eCollection 2014 Dec.

Abstract

The Type VI secretion system (T6SS) mediates toxin delivery into both eukaryotic and prokaryotic cells. It is composed of a cytoplasmic structure resembling the tail of contractile bacteriophages anchored to the cell envelope through a membrane complex composed of the TssL and TssM inner membrane proteins and of the TssJ outer membrane lipoprotein. The C-terminal domain of TssM is required for its interaction with TssJ, and for the function of the T6SS. In Citrobacter rodentium, the tssM1 gene does not encode the C-terminal domain. However, the stop codon is preceded by a run of 11 consecutive adenosines. In this study, we demonstrate that this poly-A tract is a transcriptional slippery site that induces the incorporation of additional adenosines, leading to frameshifting, and hence the production of two TssM1 variants, including a full-length canonical protein. We show that both forms of TssM1, and the ratio between these two forms, are required for the function of the T6SS in C. rodentium. Finally, we demonstrate that the tssM gene associated with the Yersinia pseudotuberculosis T6SS-3 gene cluster is also subjected to transcriptional frameshifting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / genetics
  • Bacterial Secretion Systems / genetics*
  • Bacterial Secretion Systems / metabolism
  • Base Sequence
  • Citrobacter rodentium / genetics*
  • Citrobacter rodentium / metabolism*
  • Codon, Nonsense*
  • Frameshift Mutation / physiology*
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Organisms, Genetically Modified
  • Protein Isoforms / genetics
  • Sequence Analysis, DNA
  • Suppression, Genetic

Substances

  • Bacterial Proteins
  • Bacterial Secretion Systems
  • Codon, Nonsense
  • Membrane Proteins
  • Protein Isoforms

Grant support

Work in EC laboratory is supported by the CNRS, the Aix-Marseille Université and a grant from the Agence National de la Recherche (ANR-10-JCJC-1303-03). JFA was supported by a grant from Science Foundation Ireland. EG was supported by a postdoctoral fellowship from the Fondation pour la Recherche Medicale (SPF-2009-12-17571). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.