Table 2.

Summary of the distinct mechanisms of PRMT5 regulation.

Regulation	Regulators	Mechanism	Effect	Reference
PTMs	Coactivator-associated arginine methyltransferase 1 (CARM1)	Methylation of R505	Promotes PRMT5 homodimerization	[34]
	Protein kinase B/Akt	Phosphorylation of T634	Aids interaction with 14-3-3-proteins	[35]
	Janus kinase 2 (JAK2)	Phosphorylation of Y304 and Y307	Increases substrate binding
	Protein Kinase C iota (PKCι)	Phosphorylation of S15	Promotes NF-κB activation	[36]
	Liver kinase B1 (LKB1)	Phosphorylation of T139 and T144	Increases methyltransferase activity and interaction with co-factors	[37]
miRNAs	miR-19a, miR-25, miR-32 miR-92b, and miR-96	Binds to 3′UTR of PRMT5 mRNA	Reduces PRMT5 levels	[40]
Protein Interactions	Coordinator Of PRMT5 (COPR5)	Serves as an adaptor for PRMT5 recruitment to chromatin	Causes PRMT5 preferential methylation of H4R3	[42]
	Human SWItch/Sucrose Non-Fermentable (hSWI/SNF)	Recruits PRMT5 to H3R8 and H4R3 at ST7 and NM23 promoters	Reduces expression of ST7 and NM23	[43]
	Methyl-CpG-binding domain protein 2/nucleosome remodeling and deacetylase (MBD2/NuRD)	Recruits PRMT5 to CpG islands of p14ARF and p16INK4a	Reduces expression of p14ARF and p16INK4a	[44]
	Menin	Recruits PRMT5 to Gas1 promoter	Reduces Gas1 gene expression and enhances Sonic Hedgehog signaling	[45]
	B-Lymphocyte induced maturation protein-1 (Blimp1)	Recruits PRMT5 to H2AR3 and H4R3	Repression of genes in cell cycle, cell signaling, metabolism and transcription	[46]
	pICln	Recruits PRMT5 to H4R3 and spliceosomal proteins	Repression of genes in DNA double-stranded break; Assembly of pre-mRNA splicing machinery	[48,49]
	RIO kinase 1 (RioK1)	Recruits PRMT5 to nucleolin for methylation	Ribosomal synthesis and maturation	[50]