The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium
ABSTRACT FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogene...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-02-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02504-18 |
| _version_ | 1818424694995419136 |
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| author | Alexander J. Westermann Elisa Venturini Mikael E. Sellin Konrad U. Förstner Wolf-Dietrich Hardt Jörg Vogel |
| author_facet | Alexander J. Westermann Elisa Venturini Mikael E. Sellin Konrad U. Förstner Wolf-Dietrich Hardt Jörg Vogel |
| author_sort | Alexander J. Westermann |
| collection | DOAJ |
| description | ABSTRACT FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone in Salmonella, Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3′UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs. IMPORTANCE The protein ProQ has recently been discovered as the centerpiece of a previously overlooked “third domain” of small RNA-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria. |
| first_indexed | 2024-12-14T14:02:07Z |
| format | Article |
| id | doaj.art-6dd8c7b94485478dae18e18aeea7d1ab |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T14:02:07Z |
| publishDate | 2019-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-6dd8c7b94485478dae18e18aeea7d1ab2022-12-21T22:58:42ZengAmerican Society for MicrobiologymBio2150-75112019-02-0110110.1128/mBio.02504-18The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar TyphimuriumAlexander J. Westermann0Elisa Venturini1Mikael E. Sellin2Konrad U. Förstner3Wolf-Dietrich Hardt4Jörg Vogel5Helmholtz Institute for RNA-based Infection Research (HIRI), Würzburg, GermanyInstitute of Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, GermanyInstitute of Microbiology, ETH Zürich, Zürich, SwitzerlandCore Unit Systems Medicine, University of Würzburg, Würzburg, GermanyInstitute of Microbiology, ETH Zürich, Zürich, SwitzerlandHelmholtz Institute for RNA-based Infection Research (HIRI), Würzburg, GermanyABSTRACT FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone in Salmonella, Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3′UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs. IMPORTANCE The protein ProQ has recently been discovered as the centerpiece of a previously overlooked “third domain” of small RNA-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria.https://journals.asm.org/doi/10.1128/mBio.02504-18Hfqnoncoding RNAProQRNA-seqbacterial pathogenposttranscriptional control |
| spellingShingle | Alexander J. Westermann Elisa Venturini Mikael E. Sellin Konrad U. Förstner Wolf-Dietrich Hardt Jörg Vogel The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium mBio Hfq noncoding RNA ProQ RNA-seq bacterial pathogen posttranscriptional control |
| title | The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium |
| title_full | The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium |
| title_fullStr | The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium |
| title_full_unstemmed | The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium |
| title_short | The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium |
| title_sort | major rna binding protein proq impacts virulence gene expression in named content content type genus species salmonella enterica named content serovar typhimurium |
| topic | Hfq noncoding RNA ProQ RNA-seq bacterial pathogen posttranscriptional control |
| url | https://journals.asm.org/doi/10.1128/mBio.02504-18 |
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