Structural Insights into RNase J That Plays an Essential Role in Mycobacterium Tuberculosis RNA Metabolism

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Apr 20

PMID 37080992

Authors

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

Jixi Li

Affiliations

Soon will be listed here.

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.

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References

Plocinski P, Macios M, Houghton J, Niemiec E, Plocinska R, Brzostek A . Proteomic and transcriptomic experiments reveal an essential role of RNA degradosome complexes in shaping the transcriptome of Mycobacterium tuberculosis. Nucleic Acids Res. 2019; 47(11):5892-5905. PMC: 6582357. DOI: 10.1093/nar/gkz251. View

Kushner S . mRNA decay in Escherichia coli comes of age. J Bacteriol. 2002; 184(17):4658-65; discussion 4657. PMC: 135271. DOI: 10.1128/JB.184.17.4658-4665.2002. View

Huang H, Ding N, Yang T, Li C, Jia X, Wang G . Cross-sectional Whole-genome Sequencing and Epidemiological Study of Multidrug-resistant Mycobacterium tuberculosis in China. Clin Infect Dis. 2018; 69(3):405-413. PMC: 6637280. DOI: 10.1093/cid/ciy883. View

Taverniti V, Forti F, Ghisotti D, Putzer H . Mycobacterium smegmatis RNase J is a 5'-3' exo-/endoribonuclease and both RNase J and RNase E are involved in ribosomal RNA maturation. Mol Microbiol. 2011; 82(5):1260-76. DOI: 10.1111/j.1365-2958.2011.07888.x. View

Durand S, Gilet L, Bessieres P, Nicolas P, Condon C . Three essential ribonucleases-RNase Y, J1, and III-control the abundance of a majority of Bacillus subtilis mRNAs. PLoS Genet. 2012; 8(3):e1002520. PMC: 3297567. DOI: 10.1371/journal.pgen.1002520. View

Liu T, Tsai S, Chen J, Wang Y, Hu S, Chen Y . Is a Homologue of RNase J and Plays a Role in Colony Morphotype, Aggregation, and Sliding Motility of . Microorganisms. 2021; 9(4). PMC: 8064342. DOI: 10.3390/microorganisms9040676. View

Liu Y, Wang H, Cui T, Zhou X, Jia Y, Zhang H . NapM, a new nucleoid-associated protein, broadly regulates gene expression and affects mycobacterial resistance to anti-tuberculosis drugs. Mol Microbiol. 2016; 101(1):167-81. DOI: 10.1111/mmi.13383. View

Hicks N, Yang J, Zhang X, Zhao B, Grad Y, Liu L . Clinically prevalent mutations in Mycobacterium tuberculosis alter propionate metabolism and mediate multidrug tolerance. Nat Microbiol. 2018; 3(9):1032-1042. PMC: 6233875. DOI: 10.1038/s41564-018-0218-3. View

Arraiano C, Andrade J, Domingues S, Guinote I, Malecki M, Matos R . The critical role of RNA processing and degradation in the control of gene expression. FEMS Microbiol Rev. 2010; 34(5):883-923. DOI: 10.1111/j.1574-6976.2010.00242.x. View

10.

Newman J, Hewitt L, Rodrigues C, Solovyova A, Harwood C, Lewis R . Unusual, dual endo- and exonuclease activity in the degradosome explained by crystal structure analysis of RNase J1. Structure. 2011; 19(9):1241-51. DOI: 10.1016/j.str.2011.06.017. View

11.

Mathy N, Benard L, Pellegrini O, Daou R, Wen T, Condon C . 5'-to-3' exoribonuclease activity in bacteria: role of RNase J1 in rRNA maturation and 5' stability of mRNA. Cell. 2007; 129(4):681-92. DOI: 10.1016/j.cell.2007.02.051. View

12.

Zhao Y, Lu M, Zhang H, Hu J, Zhou C, Xu Q . Structural insights into catalysis and dimerization enhanced exonuclease activity of RNase J. Nucleic Acids Res. 2015; 43(11):5550-9. PMC: 4477667. DOI: 10.1093/nar/gkv444. View

13.

Romano M, van de Weerd R, Brouwer F, Roviello G, Lacroix R, Sparrius M . Structure and function of RNase AS, a polyadenylate-specific exoribonuclease affecting mycobacterial virulence in vivo. Structure. 2014; 22(5):719-30. DOI: 10.1016/j.str.2014.01.014. View

14.

Zhang H, Li D, Zhao L, Fleming J, Lin N, Wang T . Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nat Genet. 2013; 45(10):1255-60. DOI: 10.1038/ng.2735. View

15.

Kumar G, Galanis C, Batchelder H, Townsend C, Lamichhane G . Penicillin Binding Proteins and β-Lactamases of Mycobacterium tuberculosis: Reexamination of the Historical Paradigm. mSphere. 2022; 7(1):e0003922. PMC: 8865919. DOI: 10.1128/msphere.00039-22. View

16.

Brem J, Panduwawala T, Ulf Hansen J, Hewitt J, Liepins E, Donets P . Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors. Nat Chem. 2021; 14(1):15-24. DOI: 10.1038/s41557-021-00831-x. View

17.

Lalvani A, Pareek M . A 100 year update on diagnosis of tuberculosis infection. Br Med Bull. 2009; 93:69-84. DOI: 10.1093/bmb/ldp039. View

18.

Dorleans A, Li de la Sierra-Gallay I, Piton J, Zig L, Gilet L, Putzer H . Molecular basis for the recognition and cleavage of RNA by the bifunctional 5'-3' exo/endoribonuclease RNase J. Structure. 2011; 19(9):1252-61. DOI: 10.1016/j.str.2011.06.018. View

19.

Ow M, Kushner S . Initiation of tRNA maturation by RNase E is essential for cell viability in E. coli. Genes Dev. 2002; 16(9):1102-15. PMC: 186257. DOI: 10.1101/gad.983502. View

20.

Lei X, Fan Q, Huang T, Liu H, Zhao G, Ding X . Efficient circular gene knockout system for Burkholderiales strain DSM 7029 and Mycobacterium smegmatis mc2 155. Acta Biochim Biophys Sin (Shanghai). 2019; 51(7):697-706. DOI: 10.1093/abbs/gmz054. View