Bcdin3d-KO Mouse

BCDIN3D, a member of the Bin3 methyltransferase family, is an RNA phospho-methyltransferase conserved from worm to human [1]. It methylates the 5' monophosphate of specific RNAs, including cytoplasmic tRNAHis and certain precursor microRNAs [1,2,4,6]. This methylation can regulate RNA processing and function, potentially influencing various biological processes such as miRNA biogenesis, metabolism, and cell proliferation [2,6]. Genetic models, like Drosophila ortholog studies, can be valuable in further understanding its functions [5].

In Drosophila, ovary-specific knockdown of the BCDIN3D ortholog causes female sterility and dysregulates miRNA and mRNA profiles, with many affected genes involved in metabolic processes, ribonucleoprotein complex regulation, and translational control [5]. In human breast cancer cells, BCDIN3D depletion leads to increased levels of Fructose 1,6 Bisphosphate due to down-regulation of Aldolase C, and it regulates Aldolase C through a let-7 microRNA-related mechanism [2]. Also, in cervical cancer cells, miR-195-3p inhibits cell proliferation by targeting BCDIN3D [3].

Overall, BCDIN3D plays crucial roles in RNA processing, especially of tRNAHis and miRNAs, and is involved in biological processes like female fertility in Drosophila. In human cancers, such as breast and cervical cancer, BCDIN3D is associated with disease-related phenotypes. Studies using gene knockdown models in different organisms have revealed its functions in specific biological processes and disease-related pathways, highlighting its potential as a therapeutic target.

References:

1. Tomita, Kozo, Liu, Yining. 2018. Human BCDIN3D Is a Cytoplasmic tRNAHis-Specific 5'-Monophosphate Methyltransferase. In Frontiers in genetics, 9, 305. doi:10.3389/fgene.2018.00305. https://pubmed.ncbi.nlm.nih.gov/30127802/

2. Reinsborough, Calder W, Ipas, Hélène, Abell, Nathan S, Van Den Berg, Carla, Xhemalçe, Blerta. 2021. BCDIN3D RNA methyltransferase stimulates Aldolase C expression and glycolysis through let-7 microRNA in breast cancer cells. In Oncogene, 40, 2395-2406. doi:10.1038/s41388-021-01702-y. https://pubmed.ncbi.nlm.nih.gov/33664453/

3. Jin, Minfei, Wang, Lei, Zheng, Tao, Sheng, Rong, Zhu, Hong. 2020. MiR-195-3p inhibits cell proliferation in cervical cancer by targeting BCDIN3D. In Journal of reproductive immunology, 143, 103211. doi:10.1016/j.jri.2020.103211. https://pubmed.ncbi.nlm.nih.gov/33157501/

4. Martinez, Anna, Yamashita, Seisuke, Nagaike, Takashi, Suzuki, Tsutomu, Tomita, Kozo. . Human BCDIN3D monomethylates cytoplasmic histidine transfer RNA. In Nucleic acids research, 45, 5423-5436. doi:10.1093/nar/gkx051. https://pubmed.ncbi.nlm.nih.gov/28119416/

5. Zhu, Li, Liao, Susan E, Ai, Yiwei, Fukunaga, Ryuya. 2019. RNA methyltransferase BCDIN3D is crucial for female fertility and miRNA and mRNA profiles in Drosophila ovaries. In PloS one, 14, e0217603. doi:10.1371/journal.pone.0217603. https://pubmed.ncbi.nlm.nih.gov/31145769/

6. Xhemalce, Blerta, Robson, Samuel C, Kouzarides, Tony. . Human RNA methyltransferase BCDIN3D regulates microRNA processing. In Cell, 151, 278-88. doi:10.1016/j.cell.2012.08.041. https://pubmed.ncbi.nlm.nih.gov/23063121/