PRMT5, A Pivotal Player in Cancer

Review Article

Austin J Pharmacol Ther. 2014; 2 (2).1014

PRMT5, A Pivotal Player in Cancer

Rasika Mundade1, Han Wei1 and Tao Lu1,2,*

1Department of Pharmacology and Toxicology; Indiana University School of Medicine, USA

2Department of Biochemistry and Molecular Biology; Indiana University School of Medicine, USA

*Corresponding author: : Tao Lu, Department of Pharmacology and Toxicology; Indiana University School of Medicine, Indianapolis, USA

Received: February 03, 2014; Accepted: February 10, 2014; Published: February 13, 2014


Protein arginine methyltransferases (PRMTs) are a family of enzymes that can add one or two methyl groups to the guanidino nitrogen atoms of arginine residues on histones and non–histone proteins. The abundant epigenetic modifications brought about by PRMTs help them regulate a wide variety of cellular functions, including RNA metabolism, transcriptional regulation, signal transduction, embryonic development and DNA damage repair, etc. Overexpression of different PRMTs has been frequently associated with many human cancers. Recently, increasing evidence suggests that PRMT5, an important member of the PRMT family, is a potential oncoprotein and is involved in tumorigenesis. Thus PRMT5 is an important target for therapeutic strategies. In this review, we present and discuss recent developments in our understanding of PRMT5 and its role in cancer.

Keywords Arginine, Cancer, Epigenetic regulation, Protein arginine methyltransferases


aDMA– asymmetric dimethylarginine; AdoHcy– S–adenosyl homocysteine; AdoMet–S–adenosyl methionine; AKT–protein kinase B; AMI–1–protein arginine N–methyltransferase inhibitor 1; Ash2Labsent, small, or homeotic–like (Drosophila); CBP–CREB binding protein; CDK–cyclin–dependent kinase; CF Im68–cleavage factor Im68; COPR5–cooperator of PRMT5; CRAF–a member of the Raf kinase family of serine⁄threonine–specific protein kinases; CREBcAMP response element–binding protein; DNA–deoxyribonucleic acid; EBNA–Epstein–Barr virus nuclear antigen; EGFR–epidermal growth factor receptor; E2F–transcription factor in higher eukaryotes; FGFR–fibroblast growth factor receptor; HIF–hypoxia inducible factor; HoxA–homeobox protein A; JAK–Janus kinase; JBP–Janus kinase–binding protein; LSm–like Sm; MBP– myelin basic protein; Mep–methylosome protein; Men 1–multiple endocrine neoplasia type 1; MMA–monomethylarginine; NF–κB–nuclear factor κB; NM–nonmetastatic protein; PDCD–programmed cell death protein; p53–tumor suppressor 53; PI3K–phosphoinositide 3–kinase; PRC–polycomb repressive complex; PRMTs–protein arginine methyltransferases; R–arginine; Rad9–human homologue of cell cycle checkpoint control protein S. Pombe Rad9; Rb– retinoblastoma protein; RNA–ribonucleic acid; Saos–sarcoma osteogenic; sDMAsymmetric dimethylarginine; SHP–small heterodimer partner; Smsmall nuclear ribonucleoprotein–associated protein; snRNPs–small nuclear ribonucleoproteins; SPT–suppressor of Ty; ST–suppressor of tumorigenicity protein; SWI⁄SNF–SWItch⁄Sucrose nonfermentable; TIM–triosephosphate isomerase.


Arginine methylation is a common post–translational modification catalyzed by a family of intracellular enzymes termed protein arginine methyltransferases (PRMTs). PRMTs belong to the class of AdoMet (S–adenosyl–l–methionine) –dependent methyltransferases. PRMTs utilize AdoMet as a ubiquitous cofactor to catalyze highly specific methyl group transfers from methyl donor AdoMet, to the arginine residues on different biological targets. To date, ten PRMTs have been found in mammalian cells [1]. Based on the products of the enzymatic reactions, PRMTs can be classified as type I – IV enzymes. Type I enzymes catalyze the formation of ω–NG monomethylarginine (ωMMA) and asymmetric ω–NG, NG–dimethylarginine (ω–aDMA); Type II enzymes catalyze the formation of ωMMA and symmetric ω–NG, NG–dimethylarginine (ω–sDMA); Type III enzymes catalyze the formation of ωMMA only [2], and Type IV enzymes catalyze the formation of δ–NG–MMA [3]. PRMT5 is a typical type II methyltransferase (Figure 1). It is localized in both the nucleus and the cytoplasm and performs distinct functions by modifying either histones or non–histone proteins. For example, a study by Friesen WJ et al [4]demonstrated that, in the cytoplasm, PRMT5 is present in the ‘methylosome’ where it methylates Sm protein and such methylation is required for the assembly and biogenesis of snRNP core particles. Pal S et al [5]showed that, nuclear PRMT5 forms the complexes with the hSWI⁄SNF chromatin–remodeling proteins to methylate histone H3R8, therefore, decreasing the expression of tumor suppressor genes and acting as an oncogene. Fabbrizio’s group [6] identified a nuclear protein COPR5 (cooperator of PRMT5) which is required for nuclear functions of PRMT5. PRMT5 has also been shown to translocate from the nucleus to the cytoplasm at the time of extensive epigenetic reprogramming of mouse germ cells [7]. Study by Zhao Q et al [8] suggested that PRMT5 is predominantly localized in the nucleus in the bone marrow progenitors, whereas primarily localizedin the cytoplasm in the cord blood progenitors and may play a developmentally specific role in regulating gene expression at thehuman β–globin locus.

Citation: Mundade R, Wei H, Lu T. PRMT5, A Pivotal Player in Cancer. Austin J Pharmacol Ther. 2014; 2 (2). 1014. ISSN: 2373-6208.