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...

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Autores principales:	Alexander J. Westermann, Elisa Venturini, Mikael E. Sellin, Konrad U. Förstner, Wolf-Dietrich Hardt, Jörg Vogel
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Hfq noncoding RNA ProQ RNA-seq bacterial pathogen posttranscriptional control Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6dd8c7b94485478dae18e18aeea7d1ab
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spelling	oai:doaj.org-article:6dd8c7b94485478dae18e18aeea7d1ab2021-11-15T15:55:14ZThe Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium10.1128/mBio.02504-182150-7511https://doaj.org/article/6dd8c7b94485478dae18e18aeea7d1ab2019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02504-18https://doaj.org/toc/2150-7511ABSTRACT 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.Alexander J. WestermannElisa VenturiniMikael E. SellinKonrad U. FörstnerWolf-Dietrich HardtJörg VogelAmerican Society for MicrobiologyarticleHfqnoncoding RNAProQRNA-seqbacterial pathogenposttranscriptional controlMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hfq noncoding RNA ProQ RNA-seq bacterial pathogen posttranscriptional control Microbiology QR1-502
spellingShingle	Hfq noncoding RNA ProQ RNA-seq bacterial pathogen posttranscriptional control Microbiology QR1-502 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
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.
format	article
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
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_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_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_sort	major rna-binding protein proq impacts virulence gene expression in <named-content content-type="genus-species">salmonella enterica</named-content> serovar typhimurium
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/6dd8c7b94485478dae18e18aeea7d1ab
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The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium

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