State Key Laboratory of Genetic Engineering, School of Life Sciences and Huashan Hospital, Shanghai Engineering Research Center of Industrial Microorganisms, Engineering Research Center of Gene Technology of MOE, Fudan University, 200438, Shanghai, China.
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 200438, Shanghai, China.
Nat Commun. 2023 Apr 20;14(1):2280. doi: 10.1038/s41467-023-38045-z.
Ribonucleases (RNases) are responsible for RNA metabolism. RNase J, the core enzyme of the RNA degradosome, plays an essential role in global mRNA decay. Emerging evidence showed that the RNase J of Mycobacterium tuberculosis (Mtb-RNase J) could be an excellent target for treating Mtb infection. Here, crystal structures of Mtb-RNase J in apo-state and complex with the single-strand RNA reveal the conformational change upon RNA binding and hydrolysis. Mtb-RNase J forms an active homodimer through the interactions between the β-CASP and the β-lactamase domain. Knockout of RNase J slows the growth rate and changes the colony morphologies and cell length in Mycobacterium smegmatis, which is restored by RNase J complementation. Finally, RNA-seq analysis shows that the knockout strain significantly changes the expression levels of 49 genes in metabolic pathways. Thus, our current study explores the structural basis of Mtb-RNase J and might provide a promising candidate in pharmacological treatment for tuberculosis.
核糖核酸酶（RNases）负责 RNA 代谢。RNA 降解酶核心酶 RNase J 在全局 mRNA 降解中发挥着重要作用。新出现的证据表明，结核分枝杆菌（Mtb-RNase J）的 RNase J 可能是治疗结核分枝杆菌感染的理想靶点。本研究通过解析 Mtb-RNase J 的 apo 状态和与单链 RNA 复合物的晶体结构，揭示了其在 RNA 结合和水解过程中的构象变化。Mtb-RNase J 通过 β-CASP 和β-内酰胺酶结构域之间的相互作用形成活性同源二聚体。敲除 Mtb-RNase J 会减缓分枝杆菌生长速度并改变分枝杆菌的菌落形态和细胞长度，而 Mtb-RNase J 的补充则可以恢复这些表型。最后，RNA-seq 分析表明，敲除菌株显著改变了代谢途径中 49 个基因的表达水平。因此，本研究探索了 Mtb-RNase J 的结构基础，为结核病的药物治疗提供了一个有前景的候选靶点。
