Biological function molecular pathways and druggability of DNMT2/TRDMT1

Huari Li; Huiru Liu; Daiyun Zhu; Chengli Dou; Baocai Gang; Mengjie Zhang; Ziyu Wan

doi:10.1016/j.phrs.2024.107222

Biological function molecular pathways and druggability of DNMT2/TRDMT1

Pharmacol Res. 2024 May 21:205:107222. doi: 10.1016/j.phrs.2024.107222. Online ahead of print.

Authors

Huari Li¹, Huiru Liu², Daiyun Zhu³, Chengli Dou², Baocai Gang², Mengjie Zhang², Ziyu Wan²

Affiliations

¹ Department of Biochemistry and Molecular Biology, College of Laboratory Medicine, Anhui Province Key Laboratory of Cancer Translational Medicine, and The First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, No.2600 Donghai Avenue, Bengbu, Anhui Province 233030, PR China; College of Veterinary Medicine, Huazhong Agricultural University, No.1 Shizishan Street, Wuhan, Hubei Province 430070, PR China. Electronic address: lihuari132@bbmc.edu.cn.
² Department of Biochemistry and Molecular Biology, College of Laboratory Medicine, Anhui Province Key Laboratory of Cancer Translational Medicine, and The First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, No.2600 Donghai Avenue, Bengbu, Anhui Province 233030, PR China.
³ College of Veterinary Medicine, Huazhong Agricultural University, No.1 Shizishan Street, Wuhan, Hubei Province 430070, PR China; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.

PMID: 38782147
DOI: 10.1016/j.phrs.2024.107222

Abstract

5-methylcytosine (m⁵C) is among the most common epigenetic modification in DNA and RNA molecules, and plays an important role in the animal development and disease pathogenesis. Interestingly, unlike other m⁵C DNA methyltransferases (DNMTs), DNMT2/TRDMT1 has the double-substrate specificity and adopts a DNMT-similar catalytic mechanism to methylate RNA. Moreover, it is widely involved in a variety of physiological regulatory processes, such as the gene expression, precise protein synthesis, immune response, and disease occurrence. Thus, comprehending the epigenetic mechanism and function of DNMT2/TRDMT1 will probably provide new strategies to treat some refractory diseases. Here, we discuss recent studies on the spatiotemporal expression pattern and post-translational modifications of DNMT2/TRDMT1, and summarize the research advances in substrate characteristics, catalytic recognition mechanism, DNMT2/TRDMT1-related genes or proteins, pharmacological application, and inhibitor development. This review will shed light on the pharmacological design by targeting DNMT2/TRDMT1 to treat parasitic, viral and oncologic diseases.

Keywords: Catalytic mechanism; DNMT2/TRDMT1; Disease pathogenesis; Inhibitor development; Methylation modification.

Publication types

Review