Restricted tRNA methylation by intermolecular disulfide bonds in DNMT2/TRDMT1
Copyright © 2023 Elsevier B.V. All rights reserved..
Reportedly, DNMT2/TRDMT1 mainly methylates tRNAs at C38 and prevents them from the cleavage under stress. It also plays an essential role in the survival and physiological homeostasis of organisms. Nevertheless, DNMT2/TRDMT1 exhibits much weaker tRNA methylation activity in vitro than other tRNA methyltransferases, TrmD and Trm5. Here, we explored the restricted tRNA methylation mechanism by DNMT2/TRDMT1. In the current study, the optimized buffer C at 37 °C was the best condition for DNMT2/TRDMT1 activation. Of note, Dithiothreitol (DTT) was an indispensable component for this enzyme catalysis. Moreover, reductants took similar effects on the conformation change and oligomeric formation of DNMT2/TRDMT1. Ultimately, LC-MS/MS result revealed that C292-C292 and C292-C287 were predominant intermolecular disulfide bonds in recombinant DNMT2/TRDMT1. Notably, DNMT2/TRDMT1 existed primarily as dimers via intermolecular disulfide bonds C79-C24, C292-C292, and C222-C24 in HEK293T cells. GSSG stress enhanced tRNA methylation level in the early stage of stress, whereas the DNMT2/TRDMT1 activity might be unfavorable along with this enzyme accumulation in the nucleus. Excitingly, GSH stress downregulated the DNMT2/TRDMT1 expression and promoted tRNA methylation in cells, probably through breaking intermolecular disulfide bonds in this enzyme. Thus, our findings demonstrated restricted tRNA methylation by disulfide bonds in DNMT2/TRDMT1, and will provide important implications for redox stress related-diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:251 |
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| Enthalten in: |
International journal of biological macromolecules - 251(2023) vom: 12. Aug., Seite 126310 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Huari [VerfasserIn] |
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| Links: |
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| Themen: |
DNMT2/TRDMT1 |
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| Anmerkungen: |
Date Revised 18.08.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.ijbiomac.2023.126310 |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a Reportedly, DNMT2/TRDMT1 mainly methylates tRNAs at C38 and prevents them from the cleavage under stress. It also plays an essential role in the survival and physiological homeostasis of organisms. Nevertheless, DNMT2/TRDMT1 exhibits much weaker tRNA methylation activity in vitro than other tRNA methyltransferases, TrmD and Trm5. Here, we explored the restricted tRNA methylation mechanism by DNMT2/TRDMT1. In the current study, the optimized buffer C at 37 °C was the best condition for DNMT2/TRDMT1 activation. Of note, Dithiothreitol (DTT) was an indispensable component for this enzyme catalysis. Moreover, reductants took similar effects on the conformation change and oligomeric formation of DNMT2/TRDMT1. Ultimately, LC-MS/MS result revealed that C292-C292 and C292-C287 were predominant intermolecular disulfide bonds in recombinant DNMT2/TRDMT1. Notably, DNMT2/TRDMT1 existed primarily as dimers via intermolecular disulfide bonds C79-C24, C292-C292, and C222-C24 in HEK293T cells. GSSG stress enhanced tRNA methylation level in the early stage of stress, whereas the DNMT2/TRDMT1 activity might be unfavorable along with this enzyme accumulation in the nucleus. Excitingly, GSH stress downregulated the DNMT2/TRDMT1 expression and promoted tRNA methylation in cells, probably through breaking intermolecular disulfide bonds in this enzyme. Thus, our findings demonstrated restricted tRNA methylation by disulfide bonds in DNMT2/TRDMT1, and will provide important implications for redox stress related-diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DNMT2/TRDMT1 | |
| 650 | 4 | |a Disulfide bond | |
| 650 | 4 | |a LC-MS/MS | |
| 650 | 4 | |a Redox stress | |
| 650 | 4 | |a tRNA methylation | |
| 700 | 1 | |a Zhu, Daiyun |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yapeng |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Yunfei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Pingfang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Mian |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Dandan |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Hongjing |e verfasserin |4 aut | |
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