title: Unravelling post-transcriptional PrmC-dependent regulatory mechanisms in Pseudomonas aeruginosa.
abstract: Transcriptional regulation has a central role in cellular adaptation processes and is well investigated. In contrast, the importance of the post-transcriptional regulation on these processes is less well defined. The technological advancements have been critical to precisely quantify protein and mRNA level changes and hold promise to provide more insights into how post-transcriptional regulation determines phenotypes. In Pseudomonas aeruginosa the methyltransferase PrmC methylates peptide chain release factors to facilitate translation termination. Loss of PrmC activity abolishes anaerobic growth and leads to reduced production of quorum sensing-associated virulence factors. Here, by applying SILAC technology in combination with mRNA-sequencing, they provide evidence that the P. aeruginosa phenotype can be attributed to a change in protein to mRNA ratios of selected protein groups. The UAG-dependent translation termination was more dependent on PrmC activity than the UAA- and UGA-dependent translation termination. Additionally, a bias toward UAG stop codons in global transcriptional regulators was found. The finding that this bias in stop codon usage determines the P. aeruginosa phenotype is unexpected and adds complexity to regulatory circuits. Via modulation of PrmC activity the bacterial cell can cross-regulate targets independently of transcriptional signals, a process with an underestimated impact on the bacterial phenotype.
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.|Research Core Unit Proteomics and Institute of Toxicology, Hannover Medical School, Hannover, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Krueger
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.|Department of Molecular Bacteriology, Helmholtz for Centre Infection Research, Braunschweig, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pohl
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.|Department of Molecular Bacteriology, Helmholtz for Centre Infection Research, Braunschweig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusse
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Kordes
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Rugen
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.|Department of Molecular Bacteriology, Helmholtz for Centre Infection Research, Braunschweig, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Schniederjans
authors.affiliation: Research Core Unit Proteomics and Institute of Toxicology, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pich
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany. susanne.haeussler@helmholtz-hzi.de.|Department of Molecular Bacteriology, Helmholtz for Centre Infection Research, Braunschweig, Germany. susanne.haeussler@helmholtz-hzi.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D018388:Codon, Terminator / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D010454:Peptide Termination Factors / Q000235:genetics; D010641:Phenotype; D014176:Protein Biosynthesis; D011496:Protein Methyltransferases / Q000235:genetics* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D053038:Quorum Sensing
chemical_list: D001426:Bacterial Proteins; D018388:Codon, Terminator; D010454:Peptide Termination Factors; D011496:Protein Methyltransferases