THUMPD2, a member of the RNA-binding protein (RBP) family, is an N2-methylguanosine (m2G) methyltransferase. It is crucial for the N2-methylation of U6 snRNA at G72 in the spliceosome catalytic center, which promotes efficient pre-mRNA splicing activity. This process is conserved among vertebrates. THUMPD2 is also associated with the regulation of various biological processes and is involved in multiple pathways related to cell cycle, extracellular matrix, etc. Genetic models are valuable for studying its functions [1,2,3,4].

In human cells, knockout of THUMPD2 eliminates U6 m2G72, impairs pre-mRNA splicing activity, and leads to thousands of altered alternative splicing events of endogenous pre-mRNAs. These aberrant splicing events trigger the nonsense-mediated mRNA decay pathway. In epithelial ovarian cancer, shRNA-mediated knockdown of THUMPD2 in cell lines increases cell proliferation but inhibits metastasis, while overexpression has the opposite effect. In esophageal squamous cell carcinoma cells, down-regulation of THUMPD2 is suggested to play a role in multidrug resistance [1,2,5].

In conclusion, THUMPD2 is essential for pre-mRNA splicing through its methylation of U6 snRNA. Its study using gene knockout models has revealed its significance in diseases such as age-related macular degeneration, retinal function impairment, epithelial ovarian cancer, and esophageal squamous cell carcinoma, providing insights into disease mechanisms and potential therapeutic targets.