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

Author

Listed:
  • 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
    Chinese Academy of Sciences)

  • Jixi Li

    (Fudan University
    Fudan University)

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.

Suggested Citation

  • 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 , 2023. "Structural insights into RNase J that plays an essential role in Mycobacterium tuberculosis RNA metabolism," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38045-z
    DOI: 10.1038/s41467-023-38045-z
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