A natural non-Watson-Crick base pair in human mitochondrial tRNA(Thr) causes structural and functional susceptibility to local mutations

doi:10.1093/nar/gky243

	A natural non-Watson-Crick base pair in human mitochondrial tRNA(Thr) causes structural and functional susceptibility to local mutations
	Wang, Yong1,2,3 ; Zeng, Qi-Yu 1,2; Zheng, Wen-Qiang3 ; Ji, Quan-Quan 1,2; Zhou, Xiao-Long 1,2; Wang, En-Duo1,2,3
	2018-05-18
发表期刊	NUCLEIC ACIDS RESEARCH
ISSN	0305-1048
卷号	46 期号:9 页码:4662-4676
发表状态	已发表
DOI	10.1093/nar/gky243
摘要	Six pathogenic mutations have been reported in human mitochondrial tRNA(Thr) (hmtRNA(Thr)); however, the pathogenic molecular mechanism remains unclear. Previously, we established an activity assay system for human mitochondrial threonyl-tRNA synthetase (hmThrRS). In the present study, we surveyed the structural and enzymatic effects of pathogenic mutations in hmtRNA(Thr) and then focused on m.15915 G > A (G30A) and m.15923A > G (A38G). The harmful evolutionary gain of non-Watson-Crick base pair A29/C41 caused hmtRNA(Thr) to be highly susceptible to mutations disrupting the G30-C40 base pair in various ways; for example, structural integrity maintenance, modification and aminoacylation of tRNA(Thr), and editing mischarged tRNA(Thr). A similar phenomenon was observed for hmtRNA(Trp) with an A29/C41 non-Watson-Crick base pair, but not in bovine mtRNA(Thr) with a natural G29-C41 base pair. The A38G mutation caused a severe reduction in Thr-acceptance and editing of hmThrRS. Importantly, A38 is a nucleotide determinant for the t6A modification at A37, which is essential for the coding properties of hmtRNA(Thr). In summary, our results revealed the crucial role of the G30-C40 base pair in maintaining the proper structure and function of hmtRNA(Thr) because of A29/C41 non-Watson-Crick base pair and explained the molecular outcome of pathogenic G30A and A38G mutations.
收录类别	SCI ; SCIE
语种	英语
资助项目	Youth Innovation Promotion Association (Chinese Academy of Sciences)[Y119S41291]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000433056900031
出版者	OXFORD UNIV PRESS
WOS关键词	TRANSFER-RNA SYNTHETASE ; THREONINE TRANSFER-RNA ; SACCHAROMYCES-CEREVISIAE ; IDENTITY ELEMENTS ; CODON-ANTICODON ; QUALITY-CONTROL ; HUMAN-DISEASE ; DEFICIENCY ; DEFECT ; T(6)A
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/20816
专题	生命科学与技术学院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_硕士生生命科学与技术学院_博士生
通讯作者	Zhou, Xiao-Long; Wang, En-Duo
作者单位	1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China 2.Univ Chinese Acad Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, 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	Wang, Yong,Zeng, Qi-Yu,Zheng, Wen-Qiang,et al. A natural non-Watson-Crick base pair in human mitochondrial tRNA(Thr) causes structural and functional susceptibility to local mutations[J]. NUCLEIC ACIDS RESEARCH,2018,46(9):4662-4676.
APA	Wang, Yong,Zeng, Qi-Yu,Zheng, Wen-Qiang,Ji, Quan-Quan,Zhou, Xiao-Long,&Wang, En-Duo.(2018).A natural non-Watson-Crick base pair in human mitochondrial tRNA(Thr) causes structural and functional susceptibility to local mutations.NUCLEIC ACIDS RESEARCH,46(9),4662-4676.
MLA	Wang, Yong,et al."A natural non-Watson-Crick base pair in human mitochondrial tRNA(Thr) causes structural and functional susceptibility to local mutations".NUCLEIC ACIDS RESEARCH 46.9(2018):4662-4676.