Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
ACS Chem Biol. 2020 Jul 17;15(7):1996-2004. doi: 10.1021/acschembio.0c00390. Epub 2020 Jul 2.
Bacteria are constantly adapting to their environment by sensing extracellular factors that trigger production of intracellular signaling molecules, known as second messengers. Recently, 2',3'-cyclic nucleotide monophosphates (2',3'-cNMPs) were identified in and have emerged as possible novel signaling molecules. 2',3'-cNMPs are produced through endonucleolytic cleavage of short RNAs by the T2 endoribonuclease, RNase I; however, the physiological roles of RNase I remain unclear. Our transcriptomic analysis suggests that RNase I is involved in modulating numerous cellular processes, including nucleotide metabolism, motility, acid sensitivity, metal homeostasis, and outer membrane morphology. Through a combination of deletion strain and inhibitor studies, we demonstrate that RNase I plays a previously unknown role in stress resistance by affecting pathways that are part of the defense mechanisms employed by bacteria when introduced to external threats, including antibiotics. Thus, this work provides insight into the emerging roles of RNase I in bacterial signaling and physiology and highlights the potential of RNase I as a target for antibacterial adjuvants.
细菌通过感知触发细胞内信号分子（称为第二信使）产生的细胞外因子不断适应其环境。最近，在 中鉴定出 2'，3'-环核苷酸单磷酸（2'，3'-cNMPs），并已成为可能的新型信号分子。2'，3'-cNMPs 通过 T2 内切核糖核酸酶 RNase I 对内切短 RNA 的内切核酸酶切割产生；然而，RNase I 的生理作用仍不清楚。我们的转录组分析表明，RNase I 参与调节多种细胞过程，包括核苷酸代谢、运动性、酸敏感性、金属稳态和外膜形态。通过缺失菌株和抑制剂研究的组合，我们证明 RNase I 通过影响抗生素等外部威胁引入时细菌防御机制的一部分途径，在 应激抗性中发挥以前未知的作用。因此，这项工作深入了解了 RNase I 在细菌信号转导和生理学中的新兴作用，并强调了 RNase I 作为抗菌佐剂靶标的潜力。
