Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolution
RNA methyltransferase DNMT2/TRDMT1 is the most conserved member of the DNMT family from bacteria to plants and mammals. In previous studies, we found some determinants for tRNA recognition of DNMT2/TRDMT1, but the preference mechanism of this enzyme for substrates tRNA and DNA remains to be explored...
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Taylor & Francis Group
2023-12-01
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| Series: | RNA Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15476286.2023.2272473 |
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| author | Huari Li Daiyun Zhu Yapeng Yang Yunfei Ma Yong Chen Pingfang Xue Juan Chen Mian Qin Dandan Xu Chao Cai Hongjing Cheng |
| author_facet | Huari Li Daiyun Zhu Yapeng Yang Yunfei Ma Yong Chen Pingfang Xue Juan Chen Mian Qin Dandan Xu Chao Cai Hongjing Cheng |
| author_sort | Huari Li |
| collection | DOAJ |
| description | RNA methyltransferase DNMT2/TRDMT1 is the most conserved member of the DNMT family from bacteria to plants and mammals. In previous studies, we found some determinants for tRNA recognition of DNMT2/TRDMT1, but the preference mechanism of this enzyme for substrates tRNA and DNA remains to be explored. In the present study, CFT-containing target recognition domain (TRD) and target recognition extension domain (TRED) in DNMT2/TRDMT1 play a crucial role in the substrate DNA and RNA selection during the evolution. Moreover, the classical substrate tRNA for DNMT2/TRDMT1 had a characteristic sequence CUXXCAC in the anticodon loop. Position 35 was occupied by U, making cytosine-38 (C38) twist into the loop, whereas C, G or A was located at position 35, keeping the C38-flipping state. Hence, the substrate preference could be modulated by the easily flipped state of target cytosine in tRNA, as well as TRD and TRED. Additionally, DNMT2/TRDMT1 cancer mutant activity was collectively mediated by five enzymatic characteristics, which might impact gene expressions. Importantly, G155C, G155V and G155S mutations reduced enzymatic activities and showed significant associations with diseases using seven prediction methods. Altogether, these findings will assist in illustrating the substrate preference mechanism of DNMT2/TRDMT1 and provide a promising therapeutic strategy for cancer. |
| format | Article |
| id | doaj-art-2522672e70bf403899db593f4779573b |
| institution | OA Journals |
| issn | 1547-6286 1555-8584 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | RNA Biology |
| spelling | doaj-art-2522672e70bf403899db593f4779573b2025-08-20T02:34:39ZengTaylor & Francis GroupRNA Biology1547-62861555-85842023-12-0120187589210.1080/15476286.2023.2272473Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolutionHuari Li0Daiyun Zhu1Yapeng Yang2Yunfei Ma3Yong Chen4Pingfang Xue5Juan Chen6Mian Qin7Dandan Xu8Chao Cai9Hongjing Cheng10College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaRNA methyltransferase DNMT2/TRDMT1 is the most conserved member of the DNMT family from bacteria to plants and mammals. In previous studies, we found some determinants for tRNA recognition of DNMT2/TRDMT1, but the preference mechanism of this enzyme for substrates tRNA and DNA remains to be explored. In the present study, CFT-containing target recognition domain (TRD) and target recognition extension domain (TRED) in DNMT2/TRDMT1 play a crucial role in the substrate DNA and RNA selection during the evolution. Moreover, the classical substrate tRNA for DNMT2/TRDMT1 had a characteristic sequence CUXXCAC in the anticodon loop. Position 35 was occupied by U, making cytosine-38 (C38) twist into the loop, whereas C, G or A was located at position 35, keeping the C38-flipping state. Hence, the substrate preference could be modulated by the easily flipped state of target cytosine in tRNA, as well as TRD and TRED. Additionally, DNMT2/TRDMT1 cancer mutant activity was collectively mediated by five enzymatic characteristics, which might impact gene expressions. Importantly, G155C, G155V and G155S mutations reduced enzymatic activities and showed significant associations with diseases using seven prediction methods. Altogether, these findings will assist in illustrating the substrate preference mechanism of DNMT2/TRDMT1 and provide a promising therapeutic strategy for cancer.https://www.tandfonline.com/doi/10.1080/15476286.2023.2272473DNMT2/TRDMT1tRNAsubstrate preferencegene expressionanticancer effect |
| spellingShingle | Huari Li Daiyun Zhu Yapeng Yang Yunfei Ma Yong Chen Pingfang Xue Juan Chen Mian Qin Dandan Xu Chao Cai Hongjing Cheng Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolution RNA Biology DNMT2/TRDMT1 tRNA substrate preference gene expression anticancer effect |
| title | Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolution |
| title_full | Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolution |
| title_fullStr | Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolution |
| title_full_unstemmed | Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolution |
| title_short | Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolution |
| title_sort | determinants of dnmt2 trdmt1 preference for substrates trna and dna during the evolution |
| topic | DNMT2/TRDMT1 tRNA substrate preference gene expression anticancer effect |
| url | https://www.tandfonline.com/doi/10.1080/15476286.2023.2272473 |
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