The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in Salmonella enterica Serovar Typhimurium
The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in Salmonella enterica Serovar Typhimurium
复制标题
主要 RNA 结合蛋白 ProQ 影响肠沙门氏菌鼠伤寒血清型的毒力基因表达
作者：
Westermann AJ;Venturini E;Sellin ME;Förstner KU;Hardt WD;Vogel J
FinO结构域蛋白如肠道沙门氏菌（Salmonella enterica）的ProQ已经成为细菌中一类新的主要RNA结合蛋白。ProQ已被证明靶向数百种转录本，包括来自许多毒力区域的mRNA，但其在细菌致病机制中的作用（如果有的话）尚未研究。在这里，使用双RNA-seq方法来描述沙门氏菌感染人类细胞时ProQ依赖性基因表达的变化，我们揭示了细菌运动性，趋化性和毒力基因的失调，这伴随着宿主中MAPK（丝裂原活化蛋白激酶）信号的改变。与沙门氏菌中的其他主要RNA伴侣Hfq相比，加强了这两种全局RNA结合蛋白平行工作以确保完全毒力的概念。在新发现的与感染相关的ProQ结合的小非编码RNA（sRNA）中，我们发现3′ UTR衍生的sRNA STnc 540能够以ProQ依赖的方式抑制感染诱导的镁转运蛋白mRNA。总之，这项全面的研究揭示了ProQ forSalmonellapathogenesis的相关性，并强调了RNA结合蛋白在调节细菌毒力programmes.IMPORTANCEThe蛋白ProQ最近被发现作为一个以前被忽视的“第三域”的小RNA介导的细菌基因表达控制的核心。随着体外研究不断揭示分子机制，了解ProQ如何影响细菌病原体的生命周期也很重要，因为这些病原体感染真核细胞。在这里，我们已经确定了ProQ如何塑造沙门氏菌的毒力，以及这种RNA结合蛋白的活性如何与Hfq的活性进行比较，Hfq是这种细菌和其他细菌中基于RNA的基因调控的另一种中心蛋白。为此，我们在感染期间应用病原体和宿主细胞的全局转录组学。在这样做的过程中，我们揭示了ProQ依赖的关键毒力和宿主免疫途径的转录变化。此外，我们区分的作用ProQ从Hfq在感染过程中，编码和非编码转录，并提供了一个重要的资源，为那些感兴趣的ProQ依赖的小RNA在肠道细菌。
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 asSalmonellainfects 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 inSalmonella, 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 forSalmonellapathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs.IMPORTANCEThe 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. Asin vitrowork 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 shapesSalmonellavirulence 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.
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DOI：
10.15252/embj.201696127
发表时间：
2017-04-13
期刊：
The EMBO journal
影响因子：
--
作者：
Smirnov A;Wang C;Drewry LL;Vogel J
通讯作者：
Vogel J
DOI：
10.1073/pnas.1601626113
发表时间：
2016-08-02
影响因子：
11.1
作者：
Attaiech, Laetitia;Boughammoura, Aida;Charpentier, Xavier
通讯作者：
Charpentier, Xavier
影响因子：
64.8
作者：
Westermann, Alexander J.;Foerstner, Konrad U.;Vogel, Joerg
通讯作者：
Vogel, Joerg
大肠杆菌和鼠伤寒沙门氏菌中噬菌体介导的普遍转导。
影响因子：
--
作者：
N. Sternberg;R. Maurer
通讯作者：
R. Maurer
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL