title: Transcriptional frameshifting rescues Citrobacter rodentium type VI secretion by the production of two length variants from the prematurely interrupted tssM gene.
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.
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM), Institut de Microbiologie de la Méditerranée, CNRS - Aix-Marseille Université, UMR 7255, Marseille, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Gueguen
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Norma M
authors.initials: NM
authors.lastname: Wills
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, Utah, United States of America; Departments of Biochemistry and Microbiology, University College Cork, Cork, Ireland.
authors.forename: John F
authors.initials: JF
authors.lastname: Atkins
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM), Institut de Microbiologie de la Méditerranée, CNRS - Aix-Marseille Université, UMR 7255, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Cascales
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D058947:Bacterial Secretion Systems / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D044082:Citrobacter rodentium / Q000235:genetics* / Q000378:metabolism*; D018389:Codon, Nonsense; D016368:Frameshift Mutation / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified; D020033:Protein Isoforms / Q000235:genetics; D017422:Sequence Analysis, DNA; D013489:Suppression, Genetic
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D018389:Codon, Nonsense; D008565:Membrane Proteins; D020033:Protein Isoforms