Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Department of Biological Sciences, Ohio University, Athens, OH, 45701, USA.
Nat Commun. 2022 Jun 22;13(1):3560. doi: 10.1038/s41467-022-31173-y.
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.
耐甲氧西林金黄色葡萄球菌（MRSA）是一种细菌病原体，可导致人类发病率和死亡率显著增加。小 RNA（sRNA）的转录后调控已成为控制毒力的重要机制。然而，在感染过程中，大多数 sRNA 的功能尚不清楚。为了解决这个问题，我们在 MRSA 中进行了紫外线交联、连接和杂交测序（CLASH），以鉴定在模拟宿主环境的条件下的 sRNA-RNA 相互作用。我们使用双链内切核酸酶 III 作为诱饵，发现了数百种新的 sRNA-RNA 对。引人注目的是，我们的结果表明，小膜透性毒素的产生受到广泛的 sRNA 介导的调控，其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。总之，我们对 MRSA 中的 sRNA-靶标相互作用进行了全面分析，并详细介绍了它们如何响应代谢变化来控制毒力。
