Multifaceted roles of t<SUP>6</SUP>A biogenesis in efficiency and fidelity of mitochondrial gene expression

doi:10.1093/nar/gkae013

	Multifaceted roles of t⁶A biogenesis in efficiency and fidelity of mitochondrial gene expression
	Zhang, Yong 1; Zhou, Jing-Bo 1; Yin, Yue 2; Wang, En-Duo1,3 ; Zhou, Xiao-Long 1,4
	2024
发表期刊	NUCLEIC ACIDS RESEARCH (IF:16.6[JCR-2023],16.1[5-Year])
ISSN	0305-1048
EISSN	1362-4962
发表状态	已发表
DOI	10.1093/nar/gkae013
摘要	N-6-Threonylcarbamoyladenosine at A37 (t(6)A37) of ANN-decoding transfer RNAs (tRNAs) is a universal modification whose functions have been well documented in bacteria and lower eukaryotes; however, its role in organellar translation is not completely understood. In this study, we deleted the mitochondrial t(6)A37-modifying enzyme OSGEPL1 in HEK293T cells. OSGEPL1 is dispensable for cell viability. t(6)A37 hypomodification selectively stimulated N-1-methyladenosine at A9 (m(1)A9) and N-2-methylguanosine at G10 (m(2)G10) modifications and caused a substantial reduction in the aminoacylation of mitochondrial tRNA(Thr) and tRNA(Lys), resulting in impaired translation efficiency. Multiple types of amino acid misincorporation due to the misreading of near-cognate codons by t(6)A37-unmodified tRNAs were detected, indicating a triggered translational infidelity. Accordingly, the alterations in mitochondrial structure, function, and the activated mitochondrial unfolded protein response were observed. Mitochondrial function was efficiently restored by wild-type, but not by tRNA-binding-defective OSGEPL1. Lastly, in Osgepl1 deletion mice, disruption to mitochondrial translation was evident but resulted in no observable deficiency under physiological conditions in heart, which displays the highest Osgepl1 expression. Taken together, our data delineate the multifaceted roles of mitochondrial t(6)A37 modification in translation efficiency and quality control in mitochondria.
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收录类别	SCI
语种	英语
资助项目	National Key Research and Development Program of China["2021YFA1300800","2021YFC2700903"] ; Natural Science Foundation of China["32271300","91940302","31900436"] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0570000] ; Committee of Science and Technology in Shanghai["22ZR1481300","22JC1400503"] ; CAS Project for Young Scientists in Basic Research[YSBR-075]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:001144053200001
出版者	OXFORD UNIV PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/349912
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
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 Mol Biol,Key Lab RNA Sci & Engn, 320 Yue Yang Rd, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Adv Res Inst, Natl Facil Prot Sci Shanghai, 333 Haike Rd, Shanghai 201210, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhang, Yong,Zhou, Jing-Bo,Yin, Yue,et al. Multifaceted roles of t⁶A biogenesis in efficiency and fidelity of mitochondrial gene expression[J]. NUCLEIC ACIDS RESEARCH,2024.
APA	Zhang, Yong,Zhou, Jing-Bo,Yin, Yue,Wang, En-Duo,&Zhou, Xiao-Long.(2024).Multifaceted roles of t⁶A biogenesis in efficiency and fidelity of mitochondrial gene expression.NUCLEIC ACIDS RESEARCH.
MLA	Zhang, Yong,et al."Multifaceted roles of t⁶A biogenesis in efficiency and fidelity of mitochondrial gene expression".NUCLEIC ACIDS RESEARCH (2024).