The interplay of sRNAs Hfq and RNase E in the control of gene expression; a novel mechanism linked to pathogenic bacterial virulence

sRNA Hfq 和 RNase E 在基因表达控制中的相互作用；

• 批准号: BB/F013140/1
• 负责人: Anastasia Callaghan
• 金额: $ 42.81万
• 依托单位: University of Portsmouth
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF013140%2F1
• 关键词: interplay; sRNAs; Hfq; RNase; control

With antibiotic resistance on the rise, research into understanding the workings of bacterial organisms is crucially important, as are new approaches to combating the infections they cause. When bacterial cells bring about infection, one of the first steps is that they must gain entry to the host cell. Recently scientists have found that an interlinked sequence of events occurs at the molecular level which aids the process of bacterial invasion into a host cell. They found that within the bacteria, messenger molecules (mRNA) played an important role in the invasion, but that these molecules were either degraded or stabilized by destruction (RNase E) or protection (Hfq) molecules respectively. It is also known that bacteria use signal molecules (sRNAs) to trigger either the destruction or the protection of the messenger molecules (mRNA). During the life of a bacterial cell, it is now understood that a complex sequence of interactions continually occurs between these molecules. Recent advances have taken the first steps to understanding this complex sequence of interactions, but quite how the events are communicated and regulated within the bacterial cell is still unknown. How does the destruction pathway work and how does the protector molecule prevent it? Are different signal molecules (sRNAs) treated differently? Can the protection pathway be interrupted in order to prevent the bacteria invading the host cell, and thereby preventing infection? Current data are lacking to answer these most fundamental questions. The aim of this research proposal is therefore to understand the interactions between the signal, messenger, protector and destructor molecules (sRNA, mRNA, Hfq and RNase E) found within a model bacterial cell. Only with this knowledge will it be possible to accurately inhibit the appropriate interactions to develop novel antibacterial approaches.

随着抗生素耐药性的上升，了解细菌生物体的工作机制的研究至关重要，对抗它们引起的感染的新方法也至关重要。当细菌细胞引起感染时，第一步是它们必须进入宿主细胞。最近，科学家发现在分子水平上发生了一系列相互关联的事件，这有助于细菌入侵宿主细胞的过程。他们发现，在细菌内，信使分子（mRNA）在入侵中发挥了重要作用，但这些分子分别被破坏（RNase E）或保护（Hfq）分子降解或稳定。也已知细菌使用信号分子（sRNA）来触发信使分子（mRNA）的破坏或保护。在细菌细胞的生命过程中，现在已经知道这些分子之间不断发生复杂的相互作用。最近的进展已经迈出了理解这种复杂的相互作用序列的第一步，但这些事件如何在细菌细胞内进行交流和调节仍然是未知的。破坏途径是如何工作的，保护分子又是如何阻止它的？不同的信号分子（sRNA）是否被不同地对待？为了防止细菌入侵宿主细胞，从而防止感染，是否可以中断保护途径？目前缺乏数据来回答这些最基本的问题。因此，本研究提案的目的是了解在模型细菌细胞内发现的信号，信使，保护和破坏分子（sRNA，mRNA，Hfq和RNase E）之间的相互作用。只有掌握了这些知识，才有可能准确地抑制适当的相互作用，以开发新的抗菌方法。

项目成果

The first small-molecule inhibitors of members of the ribonuclease E family.

• DOI: 10.1038/srep08028
• 发表时间: 2015-01-26
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Kime L;Vincent HA;Gendoo DM;Jourdan SS;Fishwick CW;Callaghan AJ;McDowall KJ
• 通讯作者: McDowall KJ

Hfq binding changes the structure of Escherichia coli small noncoding RNAs OxyS and RprA, which are involved in the riboregulation of rpoS.

• DOI: 10.1261/rna.034595.112
• 发表时间: 2013-08
• 期刊: RNA (New York, N.Y.)
• 作者: Henderson CA;Vincent HA;Casamento A;Stone CM;Phillips JO;Cary PD;Sobott F;Gowers DM;Taylor JEN;Callaghan AJ
• 通讯作者: Callaghan AJ

Characterization of Vibrio cholerae Hfq provides novel insights into the role of the Hfq C-terminal region.

• DOI: 10.1016/j.jmb.2012.03.028
• 发表时间: 2012-06-29
• 期刊: JOURNAL OF MOLECULAR BIOLOGY
• 影响因子: 5.6
• 作者: Vincent, Helen A.;Henderson, Charlotte A.;Ragan, Timothy J.;Garza-Garcia, Acely;Cary, Peter D.;Gowers, Darren M.;Malfois, Marc;Driscoll, Paul C.;Sobott, Frank;Callaghan, Anastasia J.
• 通讯作者: Callaghan, Anastasia J.

An improved method for surface immobilisation of RNA: application to small non-coding RNA-mRNA pairing.

• DOI: 10.1371/journal.pone.0079142
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Vincent HA;Phillips JO;Henderson CA;Roberts AJ;Stone CM;Mardle CE;Butt LE;Gowers DM;Pickford AR;Callaghan AJ
• 通讯作者: Callaghan AJ

The low-resolution solution structure of Vibrio cholerae Hfq in complex with Qrr1 sRNA.

• DOI: 10.1093/nar/gks582
• 发表时间: 2012-09-01
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Vincent HA;Henderson CA;Stone CM;Cary PD;Gowers DM;Sobott F;Taylor JEN;Callaghan AJ
• 通讯作者: Callaghan AJ