Trdmt1, also known as DNMT2, is a 5-methylcytosine methyltransferase initially classified as a DNA methyltransferase. It can methylate both tRNA and mRNA, promoting tRNA stability and proper protein synthesis, and is involved in orchestrating DNA damage response (DDR) and DNA stability [1,2]. It is widely involved in physiological regulatory processes like gene expression, precise protein synthesis, immune response, and is associated with various diseases [2]. Genetic models, such as gene knockout (KO), are valuable for studying its functions.

In cancer research, Trdmt1 KO can sensitize cancer cells of different origins to radiotherapy and chemotherapy, suggesting its role in cancer progression as its levels can be elevated and mutations can be observed in several cancer types [1]. In glioblastoma cells, Trdmt1 KO led to decreased levels of total 5-methylcytosine in DNA, DNMT1, and DNMT activity, affecting processes like telomere maintenance, cell cycle, etc. [3]. In ovarian cancer, the G155V mutation in Trdmt1 led to hyper-ubiquitination, reduced Trdmt1 levels, impaired homologous recombination, and increased sensitivity to cisplatin [4].

In conclusion, Trdmt1 plays essential roles in multiple biological processes, especially in maintaining RNA and DNA stability. Model-based research, particularly Trdmt1 KO models, has significantly contributed to understanding its role in cancer, suggesting it could be a potential target for anticancer therapy [1,3,4].

References:

1. Lewinska, Anna, Adamczyk-Grochala, Jagoda, Wnuk, Maciej. 2023. TRDMT1-mediated RNA C-5 methylation as a novel target in anticancer therapy. In Biochimica et biophysica acta. Reviews on cancer, 1878, 188964. doi:10.1016/j.bbcan.2023.188964. https://pubmed.ncbi.nlm.nih.gov/37625528/

2. Li, Huari, Liu, Huiru, Zhu, Daiyun, Zhang, Mengjie, Wan, Ziyu. 2024. Biological function molecular pathways and druggability of DNMT2/TRDMT1. In Pharmacological research, 205, 107222. doi:10.1016/j.phrs.2024.107222. https://pubmed.ncbi.nlm.nih.gov/38782147/

3. Zabek, Tomasz, Szmatola, Tomasz, Adamczyk-Grochala, Jagoda, Lewinska, Anna, Wnuk, Maciej. 2023. Knockout of TRDMT1 methyltransferase affects DNA methylome in glioblastoma cells. In Journal of neuro-oncology, 163, 61-69. doi:10.1007/s11060-023-04304-8. https://pubmed.ncbi.nlm.nih.gov/37169948/

4. Zhu, Xiaolan, Wang, Xiangyu, Yan, Wei, Li, Hong-Yu, Lan, Li. 2021. Ubiquitination-mediated degradation of TRDMT1 regulates homologous recombination and therapeutic response. In NAR cancer, 3, zcab010. doi:10.1093/narcan/zcab010. https://pubmed.ncbi.nlm.nih.gov/33778494/