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小调控RNA DsrA以依赖RpoS的方式沉默肠道致病性大肠杆菌的肠细胞脱落位点。

The small regulatory RNA DsrA silences the locus of enterocyte effacement of enteropathogenic in an RpoS-dependent manner.

作者信息

Critelli Brian, Mrozek Zoe, Mihaita Alexa, Long Lianna, Robinson Abigail, Bhatt Shantanu

机构信息

Department of Biology, Saint Joseph's University, 5600 City Avenue, Philadelphia, PA, 19131, United States.

Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA, 19104, United States.

出版信息

MicroPubl Biol. 2025 Jun 14;2025. doi: 10.17912/micropub.biology.001409. eCollection 2025.

Abstract

Attaching and effacing (A/E) pathogens adhere to intestinal cells (attachment) and destroy their microvilli (effacement). The A/E pathophenotype is encoded by a cluster of genes that are organized into the pathogenicity island called locus of enterocyte effacement (LEE). While transcriptional regulation of the LEE has been extensively interrogated in A/E pathogens, posttranscriptional regulation remains poorly understood. The RNA-binding protein Hfq and Hfq-dependent regulatory RNAs (sRNAs) play important roles in regulating the LEE posttranscriptionally. In a recent screen, we identified the Hfq-dependent sRNA DsrA as a novel riboregulator of the LEE in the A/E pathogen enteropathogenic . Our findings suggest that DsrA globally silences the LEE by negatively regulating transcription of the -encoded master regulator Ler. The repression of is mediated through the stationary phase sigma factor, RpoS. Interestingly, our results contrast with what has been previously reported on the role of DsrA in EHEC, where the sRNA activates transcription from the promoter in an RpoS-dependent manner. The contrasting regulatory role of DsrA in EPEC and EHEC underscores the need for experimental validation of sRNA networks within each lineage, rather than inferring their function based on their roles in related bacteria.

摘要

黏附和损伤(A/E)病原体黏附于肠道细胞(黏附)并破坏其微绒毛(损伤)。A/E病理表型由一组基因编码,这些基因被组织成称为肠上皮细胞损伤位点(LEE)的致病岛。虽然LEE的转录调控在A/E病原体中已被广泛研究,但转录后调控仍知之甚少。RNA结合蛋白Hfq和Hfq依赖性调控RNA(sRNA)在转录后调控LEE中起重要作用。在最近的一项筛选中,我们鉴定出Hfq依赖性sRNA DsrA是A/E病原体肠致病性大肠杆菌中LEE的一种新型核糖调节因子。我们的研究结果表明,DsrA通过负调控由Ler编码的主调节因子的转录来全局沉默LEE。Ler的抑制是通过稳定期σ因子RpoS介导的。有趣的是,我们的结果与之前关于DsrA在肠出血性大肠杆菌(EHEC)中作用的报道形成对比,在EHEC中,sRNA以RpoS依赖性方式激活来自Ler启动子的转录。DsrA在肠致病性大肠杆菌(EPEC)和EHEC中的不同调控作用强调了对每个谱系内sRNA网络进行实验验证的必要性,而不是基于它们在相关细菌中的作用来推断其功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c55e/12205375/dd53a9ed561c/25789430-2025-micropub.biology.001409.jpg

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