Activity of METTL4 Methyltransferase Is Crucial for Maintaining Optimal Splicing Efficiency in HeLa S3 Cells

Methyltransferases that modify spliceosomal small nuclear RNAs (snRNAs) play a crucial role in the cell by ensuring proper maturation of snRNAs, which is essential for optimal function of spliceosome. In this study, we investigated the enzyme METTL4, which catalyzes N6-methylation of 2'-O-methyladenosine at position 30 of U2 snRNA. Function of both the protein and the modification in splicing remains unclear. We demonstrated that inactivation of the METTL4 gene in HeLa S3 cells leads to significant changes in alternative splicing, general slowdown in spliceosome activity, and intron accumulation. In the cells lacking METTL4, expression of the set of genes associated with ribosomal RNA maturation is reduced, and the number of coilin-positive structures, most likely Cajal bodies, is decreased in the nuclei of these cells.