RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression.
RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression.
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DOI：
10.1038/s41467-022-31173-y
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发表时间：
2022-06-22
影响因子：
16.6
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中科院分区：
文献类型：
--
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耐甲氧西林金黄色葡萄球菌（MRSA）是一种细菌病原体负责重大的人类发病率和死亡率。小rna （sRNAs）的转录后调控已成为控制毒力的重要机制。然而，大多数srna在感染期间的功能是未知的。为了解决这个问题，我们在MRSA中进行了紫外交联、连接和杂交测序（CLASH），以确定模拟宿主环境条件下sRNA-RNA的相互作用。使用双链核糖核酸内切酶III作为诱饵，我们发现了数百对新的rna - rna对。引人注目的是，我们的研究结果表明，小的膜渗透性毒素的产生受到广泛的srna介导的调节，它们的表达与代谢密切相关。此外，我们还发现了RsaE和RsaI之间的sRNA海绵相互作用。综上所述，我们对MRSA中srna -靶标相互作用进行了全面分析，并提供了这些相互作用如何在代谢变化的反应中控制毒力的详细信息。调节性小RNA （sRNA）通过多种机制与mrna相互作用，调节mrna的稳定性、转录和翻译。在这里，McKellar等人利用多重耐药金黄色葡萄球菌在不同培养条件下的RNase IIICLASH，将RNA-RNA相互作用的网络与环境条件联系起来，发现小膜透性毒素的产生受到sRNAs的强烈调控。
Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen responsible for significant human morbidity and mortality. Post-transcriptional regulation by small RNAs (sRNAs) has emerged as an important mechanism for controlling virulence. However, the functionality of the majority of sRNAs during infection is unknown. To address this, we performed UV cross-linking, ligation, and sequencing of hybrids (CLASH) in MRSA to identify sRNA-RNA interactions under conditions that mimic the host environment. Using a double-stranded endoribonuclease III as bait, we uncovered hundreds of novel sRNA-RNA pairs. Strikingly, our results suggest that the production of small membrane-permeabilizing toxins is under extensive sRNA-mediated regulation and that their expression is intimately connected to metabolism. Additionally, we also uncover an sRNA sponging interaction between RsaE and RsaI. Taken together, we present a comprehensive analysis of sRNA-target interactions in MRSA and provide details on how these contribute to the control of virulence in response to changes in metabolism. Regulatory small RNA (sRNA) interact with mRNAs to regulate their stability, transcription, and translation via diverse mechanisms. Here, McKellar et al. apply RNase IIICLASH of multi-drug resistant Staphylococcus aureus under different culture conditions to link the network of RNA-RNA interactions to environmental conditions and find that the production of small membrane-permeabilizing toxins is strongly regulated by sRNAs.
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影响因子：
3.7
作者：
Beaume M;Hernandez D;Farinelli L;Deluen C;Linder P;Gaspin C;Romby P;Schrenzel J;Francois P
通讯作者：
Francois P
影响因子：
11.3
作者：
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Storz G
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作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
3.6
作者：
Beuzón, CR;Banks, G;Holden, DW
通讯作者：
Holden, DW
影响因子：
16
作者：
Bouvier, Marie;Sharma, Cynthia M.;Vogel, Joerg
通讯作者：
Vogel, Joerg