RNA Biology Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.
RNA Biology Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.
Biochem Biophys Res Commun. 2024 Nov 12;733:150688. doi: 10.1016/j.bbrc.2024.150688. Epub 2024 Sep 11.
The toxin-antitoxin (TA) system regulates many physiological processes in free-living bacteria. One such TA system in Escherichia coli comprises an RNA toxin SdsR and an antitoxin RyeA. An overabundance of SdsR is toxic to the cells. RyeA normalizes SdsR abundance and helps the cells to adapt to altered conditions. The current study showed that a novel small RNA (sRNA) regulator GcvB directly interacts with RyeA to maintain its abundance in the cells under normal or low pH conditions. The deletion of the gcvB allele in the E. coli chromosome resulted in a ∼3-fold decrease in intrabacterial RyeA accumulation. An ectopic expression of GcvB in ΔgcvB strain reinstated RyeA abundance to its normal level. Induction of GcvB in the cells upon exposure to low pH resulted in a simultaneous increase in intracellular RyeA. While GcvB increases RyeA abundance in the cells, SdsR accumulation is divergently regulated by GcvB. The absence of the gcvB gene in E. coli leads to upregulation of SdsR and vice versa. The GcvB-mediated decrease of SdsR accumulation stems from the increased RyeA-driven normalization of SdsR. This study delineates a novel mechanism for the regulation of the expression of an RNA toxin SdsR by another sRNA regulator GcvB through a feed-forward control.
毒素-抗毒素（TA）系统调节自由生活细菌中的许多生理过程。大肠杆菌中的一个这样的 TA 系统包括 RNA 毒素 SdsR 和抗毒素 RyeA。SdsR 的过量存在对细胞有毒。RyeA 使 SdsR 丰度正常化，并帮助细胞适应改变的条件。本研究表明，一种新型小 RNA（sRNA）调节剂 GcvB 直接与 RyeA 相互作用，以在正常或低 pH 条件下维持其在细胞中的丰度。在大肠杆菌染色体中缺失 gcvB 等位基因会导致细胞内 RyeA 积累减少约 3 倍。在 ΔgcvB 菌株中外源表达 GcvB 可将 RyeA 丰度恢复至正常水平。细胞暴露于低 pH 时诱导 GcvB 的表达会导致细胞内 RyeA 的同时增加。虽然 GcvB 增加了细胞内 RyeA 的丰度，但 SdsR 的积累受到 GcvB 的反向调节。在大肠杆菌中缺失 gcvB 基因会导致 SdsR 的上调，反之亦然。GcvB 介导的 SdsR 积累减少源于 RyeA 驱动的 SdsR 归一化增加。本研究通过前馈控制描绘了另一种 sRNA 调节剂 GcvB 调节 RNA 毒素 SdsR 表达的新机制。
