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| THUMPD3–TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates | |
| 2021-11-18 | |
| Source Publication | NUCLEIC ACIDS RESEARCH
 |
| ISSN | 0305-1048 |
| EISSN | 1362-4962 |
| Volume | 49Issue:20Pages:1100-11919 |
| Status | 已发表 |
| DOI | 10.1093/nar/gkab927 |
| Abstract | 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. |
| MOST Discipline Catalogue | 理学 |
| URL | 查看原文 |
| Indexed By | SCI ; SCIE |
| Language | 英语 |
| Funding Project | National Key Research and Development Program of China[2020YFA0803400] ; National Natural Science Foundation of China[32022040,31971230,31770842] |
| WOS Research Area | Biochemistry & Molecular Biology |
| WOS Subject | Biochemistry & Molecular Biology |
| WOS ID | WOS:000728384400039 |
| Publisher | OXFORD UNIV PRESS |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/133101 |
| Collection | 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 |
| Corresponding Author | Liu, Ru-Juan |
| Affiliation | 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 |
| First Author Affilication | School of Life Science and Technology |
| Corresponding Author Affilication | School of Life Science and Technology |
| First Signature Affilication | School of Life Science and Technology |
| Recommended Citation 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. |
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