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TRNA epitranscriptome determines pathogenicity of the opportunistic pathogen Pseudomonas aeruginosa

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Pseudomonas aeruginosa UCBPP-PA14 Pseudomonas aeruginosa

PROVIDER: GSE149306 | GEO | 2024/02/17

REPOSITORIES: GEO

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tRNA epitranscriptome determines pathogenicity of the opportunistic pathogen <i>Pseudomonas aeruginosa</i>.

Project description:The success of bacterial pathogens depends on the coordinated expression of virulence determinants. Regulatory circuits that drive pathogenesis are complex, multilayered, and incompletely understood. Here, we reveal that alterations in tRNA modifications define pathogenic phenotypes in the opportunistic pathogen Pseudomonas aeruginosa. We demonstrate that the enzymatic activity of GidA leads to the introduction of a carboxymethylaminomethyl modification in selected tRNAs. Modifications at the wobble uridine base (cmnm5U34) of the anticodon drives translation of transcripts containing rare codons. Specifically, in P. aeruginosa the presence of GidA-dependent tRNA modifications modulates expression of genes encoding virulence regulators, leading to a cellular proteomic shift toward pathogenic and well-adapted physiological states. Our approach of profiling the consequences of chemical tRNA modifications is general in concept. It provides a paradigm of how environmentally driven tRNA modifications govern gene expression programs and regulate phenotypic outcomes responsible for bacterial adaption to challenging habitats prevailing in the host niche.

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RNA-Seq analysis for the study "tRNA epitranscriptome determines pathogenicity of the opportunistic pathogen Pseudomonas aeruginosa"

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tRNA epitranscriptome determines pathogenicity of the opportunistic pathogen Pseudomonas aeruginosa

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tRNA epitranscriptome determines pathogenicity of the opportunistic pathogen Pseudomonas aeruginosa

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tRNA modification profiling reveals epitranscriptome regulatory networks in <i>Pseudomonas aeruginosa</i>.

Project description:Transfer RNA (tRNA) modifications have emerged as critical posttranscriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications - the tRNA epitranscriptome - very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to a Pseudomonas aeruginosa transposon insertion mutant library comprising 5,746 strains. Analysis of >200,000 tRNA modification data points validated the annotations of predicted tRNA modification genes, uncovered novel tRNA-modifying enzymes, and revealed tRNA modification regulatory networks in P. aeruginosa. Platform adaptation for RNA-seq library preparation would complement epitranscriptome studies, while application to human cell and mouse tissue demonstrates its utility for biomarker and drug discovery and development.

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