The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases

doi:10.1093/nar/gkab104

	The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases
	Peng, Gui-Xin1,2 ; Zhang, Yong 1; Wang, Qin-Qin2 ; Li, Qing-Run 3; Xu, Hong 4; Wang, En-Duo1,2 ; Zhou, Xiao-Long 1
	2021-03-18
发表期刊	NUCLEIC ACIDS RESEARCH
ISSN	0305-1048
EISSN	1362-4962
卷号	49 期号:5 页码:2816-2834
DOI	10.1093/nar/gkab104
摘要	GTPBP3 and MTO1 cooperatively catalyze 5-taurinomethyluridine (tau m(5)U) biosynthesis at the 34(th) wobble position of mitochondrial tRNAs. Mutations in tRNAs, GTPBP3 or MTO1, causing tau m(5)U hypomodification, lead to various diseases. However, efficient in vitro reconstitution and mechanistic study of tau m(5)U modification have been challenging, in part due to the lack of pure and active enzymes. A previous study reported that purified human GTPBP3 (hGTPBP3) is inactive in GTP hydrolysis. Here, we identified the mature form of hGTPBP3 and showed that hGTPBP3 is an active GTPase in vitro that is critical for tRNA modification in vivo. Unexpectedly, the isolated G domain and a mutant with the N-terminal domain truncated catalyzed GTP hydrolysis to only a limited extent, exhibiting high K-m values compared with that of the mature enzyme. We further described several important pathogenic mutations of hGTPBP3, associated with alterations in hGTPBP3 localization, structure and/or function in vitro and in vivo. Moreover, we discovered a novel cytoplasm-localized isoform of hGTPBP3, indicating an unknown potential noncanonical function of hGTPBP3. Together, our findings established, for the first time, the GTP hydrolysis mechanism of hGTPBP3 and laid a solid foundation for clarifying the tau m(5)U modification mechanism and etiology of tau m(5)U deficiency-related diseases.
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收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000637321700033
出版者	OXFORD UNIV PRESS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126815
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_王恩多组生命科学与技术学院_硕士生
通讯作者	Wang, En-Duo; Zhou, Xiao-Long
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab M, 320 Yue Yang Rd, Shanghai 200031, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Hua Xia Rd, Shanghai 201210, Peoples R China; 3.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, CAS Key Lab Syst Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China; 4.Shanghai Jiao Tong Univ, Int Peace Matern & Child Hlth Hosp, Shanghai Municipal Key Clin Specialty, Shanghai Key Lab Embryo Original Dis,Sch Med, 910 Heng Shan Rd, Shanghai 200030, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Peng, Gui-Xin,Zhang, Yong,Wang, Qin-Qin,et al. The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases[J]. NUCLEIC ACIDS RESEARCH,2021,49(5):2816-2834.
APA	Peng, Gui-Xin.,Zhang, Yong.,Wang, Qin-Qin.,Li, Qing-Run.,Xu, Hong.,...&Zhou, Xiao-Long.(2021).The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases.NUCLEIC ACIDS RESEARCH,49(5),2816-2834.
MLA	Peng, Gui-Xin,et al."The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases".NUCLEIC ACIDS RESEARCH 49.5(2021):2816-2834.