THUMPD3–TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates

doi:10.1093/nar/gkab927

	THUMPD3–TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates
	Yang, Wen-Qing1 ; Xiong, Qing-Ping 2,3; Ge, Jian-Yang1 ; Li, Hao1 ; Zhu, Wen-Yu1 ; Nie, Yan4 ; Lin, Xiuying 5; Lv, Daizhu 6; Li, Jing1 ; Lin, Huan 5; Liu, Ru-Juan1
	2021-11-18
发表期刊	NUCLEIC ACIDS RESEARCH
ISSN	0305-1048
EISSN	1362-4962
卷号	49 期号:20 页码:1100-11919
发表状态	已发表
DOI	10.1093/nar/gkab927
摘要	Post-transcriptional modifications affect tRNA biology and are closely associated with human diseases. However, progress on the functional analysis of tRNA modifications in metazoans has been slow because of the difficulty in identifying modifying enzymes. For example, the biogenesis and function of the prevalent N2-methylguanosine (m(2)G) at the sixth position of tRNAs in eukaryotes has long remained enigmatic. Herein, using a reverse genetics approach coupled with RNA-mass spectrometry, we identified that THUMP domain-containing protein 3 (THUMPD3) is responsible for tRNA: m(2)G6 formation in human cells. However, THUMPD3 alone could not modify tRNAs. Instead, multifunctional methyltransferase subunit TRM112-like protein (TRMT112) interacts with THUMPD3 to activate its methyltransferase activity. In the in vitro enzymatic assay system, THUMPD3-TRMT112 could methylate all the 26 tested G6-containing human cytoplasmic tRNAs by recognizing the characteristic 3 '-CCA of mature tRNAs. We also showed that m(2)G7 of tRNA(Trp) was introduced by THUMPD3-TRMT112. Furthermore, THUMPD3 is widely expressed in mouse tissues, with an extremely high level in the testis. THUMPD3-knockout cells exhibited impaired global protein synthesis and reduced growth. Our data highlight the significance of the tRNA: m(2)G6/7 modification and pave a way for further studies of the role of m(2)G in sperm tRNA derived fragments.
学科门类	理学
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	National Key Research and Development Program of China[2020YFA0803400] ; National Natural Science Foundation of China[32022040,31971230,31770842]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000728384400039
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/133101
专题	生命科学与技术学院_硕士生免疫化学研究所国际事务处生命科学与技术学院_博士生生命科学与技术学院_PI研究组_刘如娟组
通讯作者	Liu, Ru-Juan
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 3.Univ Chinese Acad Sci, Shanghai 200031, Peoples R China 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 5.Hainan Univ, State Key Lab Marine Resource Utilizat South Chin, Haikou, Hainan, Peoples R China 6.Chinese Acad Trop Agr Sci, Anal & Testing Ctr, Haikou 571101, Hainan, 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
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yang, Wen-Qing,Xiong, Qing-Ping,Ge, Jian-Yang,et al. THUMPD3–TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates[J]. NUCLEIC ACIDS RESEARCH,2021,49(20):1100-11919.
APA	Yang, Wen-Qing.,Xiong, Qing-Ping.,Ge, Jian-Yang.,Li, Hao.,Zhu, Wen-Yu.,...&Liu, Ru-Juan.(2021).THUMPD3–TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates.NUCLEIC ACIDS RESEARCH,49(20),1100-11919.
MLA	Yang, Wen-Qing,et al."THUMPD3–TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates".NUCLEIC ACIDS RESEARCH 49.20(2021):1100-11919.