Protein arginine methyltransferase 9 (PRMT9) (PRMT9)

Protein arginine methyltransferase 9 (PRMT9) is a type II methyltransferase that catalyzes the symmetric dimethylation of arginine residues, primarily on the splicing factor SF3B2 (also known as SAP145) (UniProt: Q6P2P2; PubMed: 26073512). By modifying SF3B2, PRMT9 regulates the assembly of the U2 small nuclear ribonucleoprotein (snRNP) complex, which is essential for accurate pre-mRNA splicing (PubMed: 26073512). PRMT9 is distinct from other PRMTs due to its unique N-terminal HEAT repeats that facilitate substrate recognition. In clinical research, PRMT9 has been identified as an oncogenic driver in several cancers, including hepatocellular carcinoma and lung adenocarcinoma, where its overexpression correlates with poor prognosis and enhanced metastatic potential (PubMed: 29151154; PubMed: 33061154). Targeting PRMT9 at the mRNA level using RNA interference (siRNA) or antisense oligonucleotides (ASOs) has shown promise in preclinical models for reducing tumor growth and reversing epithelial-mesenchymal transition (PubMed: 31435101). Although specific small-molecule inhibitors are still in the discovery phase, the PRMT9 mRNA-protein axis represents a viable therapeutic vulnerability for treating splicing-dependent malignancies.

Other names

FBXO20F-box only protein 20PRMT10Protein arginine N-methyltransferase 9

Reduction of PRMT9 protein expression through targeted mRNA degradation or translational inhibition, resulting in decreased symmetric dimethylation of the splicing factor SF3B2.