PRMT5

PRMT5, or protein arginine methyltransferase 5, is an enzyme in the arginine methyltransferase family. It is a type II PRMT that catalyzes symmetric dimethylation of arginine residues on histones and various non-histone proteins, using S-adenosylmethionine as the methyl donor. In humans, PRMT5 is encoded by the PRMT5 gene and is found in both the nucleus and cytoplasm, participating in multiple cellular processes.

PRMT5 exerts its activity largely through forming a stable complex with MEP50 (WD repeat-containing protein 77), creating the methylosome. The PRMT5–MEP50 complex methylates histone tails, notably producing symmetric dimethyl marks on histone H4 arginine 3 (H4R3me2s) and histone H3 arginine 8 (H3R8me2s), marks associated with transcriptional repression and chromatin remodeling. Beyond chromatin, PRMT5 targets a range of non-histone proteins involved in RNA processing, signaling, and the DNA damage response, affecting processes from splicing to cell signaling.

Biological roles of PRMT5 are diverse. It contributes to regulation of gene expression, RNA processing and splicing, cell cycle progression, and development. It also participates in the cellular response to stress and DNA damage, and can influence the activity of transcription factors and tumor suppressors in various contexts.

Clinical significance is underscored by its essential role in development and its frequent upregulation in cancers, where it supports tumor growth and survival. As a result, PRMT5 is a focus of therapeutic research, with several inhibitors described and evaluated in preclinical and early-phase clinical studies targeting both hematologic and solid tumors.