The essential mycobacterial amidotransferase GatCAB is a modulator of   specific translational fidelity

doi:10.1038/NMICROBIOL.2016.147

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	The essential mycobacterial amidotransferase GatCAB is a modulator of specific translational fidelity
	Su, Hong-Wei ; Zhu, Jun-Hao ; Li, Hao ; Cai, Rong-Jun ; Ealand, Christopher ; Wang, Xun ; Chen, Yu-Xiang ; Kayani, Masood Ur Rehman ; Zhu, Ting F. ; Moradigaravand, Danesh ; Huang, Hairong ; Kana, Bavesh D. ; Javid, Babak
刊名	Nature Microbiology
	2016
关键词	ELONGATION-FACTOR TU QUALITY-CONTROL GENETIC-CODE OXIDATIVE STRESS PROTEIN MISTRANSLATION ANTIBIOTIC TOLERANCE RNA TUBERCULOSIS MECHANISMS TRANSAMIDOSOME
DOI	10.1038/NMICROBIOL.2016.147
英文摘要	Although regulation of translation fidelity is an essential process(1-7), diverse organisms and organelles have differing requirements of translational accuracy(8-15), and errors in gene translation serve an adaptive function under certain conditions(16-20). Therefore, optimal levels of fidelity may vary according to context. Most bacteria utilize a two-step pathway for the specific synthesis of aminoacylated glutamine and/ or asparagine tRNAs, involving the glutamine amidotransferase GatCAB(21-25), but it had not been appreciated that GatCAB may play a role in modulating mistranslation rates. Here, by using a forward genetic screen, we show that the mycobacterial GatCAB enzyme complex mediates the translational fidelity of glutamine and asparagine codons. We identify mutations in gatA that cause partial loss of function in the holoenzyme, with a consequent increase in rates of mistranslation. By monitoring single-cell transcription dynamics, we demonstrate that reduced gatCAB expression leads to increased mistranslation rates, which result in enhanced rifampicin- specific phenotypic resistance. Consistent with this, strains with mutations in gatA from clinical isolates of Mycobacterium tuberculosis show increased mistranslation, with associated antibiotic tolerance, suggesting a role for mistranslation as an adaptive strategy in tuberculosis. Together, our findings demonstrate a potential role for the indirect tRNA aminoacylation pathway in regulating translational fidelity and adaptive mistranslation.; Bill and Melinda Gates Foundation [OPP1109789]; Tsinghua University; SCI(E); ARTICLE; bjavid@gmail.com; 11; 1
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/458569]
专题	生命科学学院
推荐引用方式 GB/T 7714	Su, Hong-Wei,Zhu, Jun-Hao,Li, Hao,et al. The essential mycobacterial amidotransferase GatCAB is a modulator of specific translational fidelity[J]. Nature Microbiology,2016.
APA	Su, Hong-Wei.,Zhu, Jun-Hao.,Li, Hao.,Cai, Rong-Jun.,Ealand, Christopher.,...&Javid, Babak.(2016).The essential mycobacterial amidotransferase GatCAB is a modulator of specific translational fidelity.Nature Microbiology.
MLA	Su, Hong-Wei,et al."The essential mycobacterial amidotransferase GatCAB is a modulator of specific translational fidelity".Nature Microbiology (2016).