TY - JOUR

T1 - Unravelling post-transcriptional PrmC-dependent regulatory mechanisms in Pseudomonas aeruginosa

AU - Krueger, Jonas

AU - Pohl, Sarah

AU - Preusse, Matthias

AU - Kordes, Adrian

AU - Rugen, Nils

AU - Schniederjans, Monika

AU - Pich, Andreas

AU - Häussler, Susanne

N1 - Funding information: We thank Karsten Heidrich for technical support, Stephan Brouwer and Christian Pustelny for providing the PA14 tnprmC and tnprmC::prmC strains and Piotr Bielecki for providing the PA14 ?lysA?argB double mutant. We also thank A. Bielecka for library preparation for RNA sequencing. This work was supported by an European Research Council starter grant (http://erc.europa.eu/, 260276), the German Research Foundation (https://www.mh-hannover.de/sfb900.html, DFG SFB 900) and Networking Fund of the Helmholtz Association of German Research Centers (HGF) under contract number VH-GS-202. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All authors have declared that no competing interests exist.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84991515464&partnerID=8YFLogxK

U2 - 10.1111/1462-2920.13435

DO - 10.1111/1462-2920.13435

M3 - Article

C2 - 27376486

AN - SCOPUS:84991515464

VL - 18

SP - 3583

EP - 3592

JO - Environmental microbiology

JF - Environmental microbiology

SN - 1462-2912

IS - 10

ER -