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目前的核糖开关景观。

The current riboswitch landscape in .

机构信息

Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France.

出版信息

Microbiology (Reading). 2024 Oct;170(10). doi: 10.1099/mic.0.001508.

DOI:10.1099/mic.0.001508
PMID:39405103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11477304/
Abstract

Riboswitches are 5' RNA regulatory elements that are capable of binding to various ligands, such as small metabolites, ions and tRNAs, leading to conformational changes and affecting gene transcription or translation. They are widespread in bacteria and frequently control genes that are essential for the survival or virulence of major pathogens. As a result, they represent promising targets for the development of new antimicrobial treatments. , a leading cause of antibiotic-associated nosocomial diarrhoea in adults, possesses numerous riboswitches in its genome. Accumulating knowledge of riboswitch-based regulatory mechanisms provides insights into the potential therapeutic targets for treating infections. This review offers an in-depth examination of the current state of knowledge regarding riboswitch-mediated regulation in , highlighting their importance in bacterial adaptability and pathogenicity. Particular attention is given to the ligand specificity and function of known riboswitches in this bacterium. The review also discusses the recent progress that has been made in the development of riboswitch-targeting compounds as potential treatments for infections. Future research directions are proposed, emphasizing the need for detailed structural and functional analyses of riboswitches to fully harness their regulatory capabilities for developing new antimicrobial strategies.

摘要

Riboswitches 是 5' RNA 调节元件,能够结合各种配体,如小分子代谢物、离子和 tRNA,导致构象变化并影响基因转录或翻译。它们广泛存在于细菌中,经常控制对主要病原体的生存或毒力至关重要的基因。因此,它们代表了开发新的抗菌治疗方法的有前途的目标。艰难梭菌是导致成人抗生素相关性医院腹泻的主要原因,其基因组中存在许多 riboswitches。关于基于 riboswitch 的调节机制的知识积累为治疗艰难梭菌感染提供了潜在的治疗靶点。这篇综述深入探讨了艰难梭菌中 riboswitch 介导的调节的最新知识状况,强调了它们在细菌适应性和致病性中的重要性。特别关注了该细菌中已知 riboswitches 的配体特异性和功能。该综述还讨论了作为艰难梭菌感染潜在治疗方法的 riboswitch 靶向化合物的最新进展。提出了未来的研究方向,强调需要对 riboswitches 进行详细的结构和功能分析,以充分利用其调节能力来开发新的抗菌策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/3e14151613e3/mic-170-01508-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/b6f7871d188d/mic-170-01508-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/1e617b67cf6b/mic-170-01508-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/f848ba1cae66/mic-170-01508-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/3b8ccb051a71/mic-170-01508-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/c871780636f7/mic-170-01508-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/3e14151613e3/mic-170-01508-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/b6f7871d188d/mic-170-01508-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/1e617b67cf6b/mic-170-01508-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/f848ba1cae66/mic-170-01508-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/3b8ccb051a71/mic-170-01508-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/c871780636f7/mic-170-01508-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f74/11477304/3e14151613e3/mic-170-01508-g006.jpg

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本文引用的文献

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Proc Natl Acad Sci U S A. 2024 Feb 6;121(6):e2318008121. doi: 10.1073/pnas.2318008121. Epub 2024 Feb 2.
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Phosphonate and Thiasugar Analogues of Glucosamine-6-phosphate: Activation of the Riboswitch and Antibiotic Activity.膦酸酯和硫代糖胺-6-磷酸类似物:对核糖开关的激活和抗生素活性。
ACS Chem Biol. 2023 Oct 20;18(10):2324-2334. doi: 10.1021/acschembio.3c00452. Epub 2023 Oct 4.
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Glycine fermentation by promotes virulence and spore formation, and is induced by host cathelicidin.
通过 发酵甘氨酸可促进毒力和孢子形成,并受宿主防御素诱导。
Infect Immun. 2023 Oct 17;91(10):e0031923. doi: 10.1128/iai.00319-23. Epub 2023 Sep 27.
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Riboswitches.核糖开关。
Curr Biol. 2023 May 8;33(9):R343-R348. doi: 10.1016/j.cub.2023.03.069.
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A network of small RNAs regulates sporulation initiation in Clostridioides difficile.一个小型 RNA 网络调控艰难梭菌孢子形成的起始。
EMBO J. 2023 Jun 15;42(12):e112858. doi: 10.15252/embj.2022112858. Epub 2023 May 4.
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Targeting Riboswitches with Beta-Axial-Substituted Cobalamins.靶向核糖开关的β-轴向取代钴胺素
ACS Chem Biol. 2023 May 19;18(5):1136-1147. doi: 10.1021/acschembio.2c00939. Epub 2023 Apr 24.
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A standalone editing protein deacylates mischarged canavanyl-tRNAArg to prevent canavanine incorporation into proteins.一种独立的编辑蛋白可以脱去错误酰化的卡那凡酰-tRNAArg,防止卡那霉素掺入蛋白质。
Nucleic Acids Res. 2023 Mar 21;51(5):2001-2010. doi: 10.1093/nar/gkac1197.
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