Protein arginine N-methyltransferase 5

Protein arginine N-methyltransferase 5 (PRMT5) is an arginine methyltransferase that catalyzes formation of monomethylarginine and symmetrical dimethylarginine on target proteins (UniProt: O14744). It mediates dimethylation of spliceosomal proteins (SNRPD1/D3) required for snRNP assembly and regulates diverse cellular processes including transcriptional elongation, histone modification, circadian gene repression, and attenuation of EGFR signaling through modification of EGFR and RAF proteins (UniProt: O14744). PRMT5 also functions in mRNA splicing and DNA–RNA hybrid resolution during transcription termination.

PRMT5 is implicated in Alzheimer's Disease pathology. Chaparral AD proteomics data from human post-mortem AD brain versus age-matched controls (TMT-labeled, four subcellular fractions) show ambiguous directionality: the protein exhibits a mean log2 fold-change of 0.054 across fractions, indicating minimal net change but variable regulation across different cellular compartments (Chaparral AD proteomics). This subtle, compartment-dependent alteration suggests PRMT5 may have complex roles in AD-associated cellular dysfunction without clear unidirectional dysregulation.