| PRMT7 is a type III protein arginine methyltransferase that catalyzes predominantly monomethylation of arginine residues on histone and non‑histone substrates and acts as a pleiotropic regulator of gene expression, stemness, stress responses, and neuromuscular development through both direct chromatin modification and crosstalk with other PRMTs, especially PRMT5. The enzyme is built around a duplicated PRMT core with two AdoMet-binding domains arranged in tandem, but only one catalytic site is active, conferring unique substrate specificity and kinetic properties within the PRMT family and favoring MMA formation that can be further converted to symmetric dimethylarginine by PRMT5. PRMT7 methylates arginine residues in glycine–arginine‑rich stretches of histones and snRNP proteins and contributes to the generation of H4R3me2s and Sm protein SDMA indirectly by activating PRMT5 or creating a priming MMA state, which influences chromatin accessibility, snRNP core assembly, and RNA processing capacity. At chromatin, PRMT7‑dependent H4R3 symmetric dimethylation has been linked to repression of DNA damage repair genes such as APEX2, POLD1, and POLD2 and to antagonism of MLL4‑mediated H3K4 methylation at neuron‑specific promoters, positioning PRMT7 as a negative regulator of subsets of repair pathways and neuronal differentiation programs. PRMT7 is enriched in embryonic stem cells, germ cells, and multiple cancer stem cell populations, where its activity supports self‑renewal and stemness by repressing differentiation‑promoting loci, modulating miRNA networks such as the miR‑24‑2 cluster, and maintaining proper levels of SDMA‑marked chromatin and RNA‑binding proteins. In cancer models, altered PRMT7 expression influences proliferation, migration, and stress tolerance: PRMT7 overexpression promotes tumor growth and survival under genotoxic or metabolic stress, while PRMT7 knockdown reduces clonogenicity, induces G1 arrest and differentiation, and sensitizes cells to DNA damaging agents, leading to increasing interest in PRMT7 as a drug target and the recent identification of dual PRMT7/9 inhibitors with defined binding modes. |
