Structural insights into RNase J that plays an essential role in Mycobacterium tuberculosis RNA metabolism

Luyao Bao, Juan Hu, Bowen Zhan, Mingzhe Chi, Zhengyang Li, Sen Wang, Chan Shan, Zhaozhao Zhao, Yanchao Guo, Xiaoming Ding, Chaoneng Ji, Shengce Tao, Ting Ni, Xuelian Zhang (), Guoping Zhao () and Jixi Li ()
Additional contact information
Luyao Bao: Fudan University
Juan Hu: Fudan University
Bowen Zhan: Fudan University
Mingzhe Chi: Fudan University
Zhengyang Li: Fudan University
Sen Wang: Fudan University
Chan Shan: Fudan University
Zhaozhao Zhao: Fudan University
Yanchao Guo: Fudan University
Xiaoming Ding: Fudan University
Chaoneng Ji: Fudan University
Shengce Tao: Shanghai Jiao Tong University
Ting Ni: Fudan University
Xuelian Zhang: Fudan University
Guoping Zhao: Fudan University
Jixi Li: Fudan University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-38045-z

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