Thumpd2-flox Mouse

THUMPD2, a member of the RNA-binding protein (RBP) family, is a methyltransferase that plays crucial roles in biological processes. It is involved in the N2-methylation of U6 snRNA at G72 in the spliceosome catalytic center, which is essential for efficient pre-mRNA splicing. This RNA epigenetic modification impacts global pre-mRNA splicing, influencing various physiological processes [1,3]. It is also associated with age-related macular degeneration and retinal function [1]. Additionally, THUMPD2 is part of the human TRMT112-methyltransferase network, with TRMT112 acting as a co-factor and activator for it [4].

In epithelial ovarian cancer, shRNA-mediated knockdown of THUMPD2 in OVCAR3 and SKOV3 cells increased cell proliferation but inhibited metastasis, while overexpression had the opposite effect. This indicates its dual function in promoting tumour metastasis in the late stage and inhibiting proliferation in the early stage [2]. In in vitro human esophageal squamous cell carcinoma cells, down-regulation of THUMPD2 was suggested to play a role in multidrug resistance to cisplatin and 5-fluorouracil [5].

In conclusion, THUMPD2 is significant for pre-mRNA splicing and has implications in diseases such as age-related macular degeneration, epithelial ovarian cancer, and esophageal squamous cell carcinoma. Studies on THUMPD2, including those using loss-of-function models in cell lines, help uncover its role in these biological processes and disease conditions, providing potential therapeutic targets.