Protein arginine methyltransferase 5

Model organisms have been used in the study of PRMT5 function. A conditional knockout mouse line, called Prmt5^{tm2a(EUCOMM)Wtsi}[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[12] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice but no further abnormalities were observed.[12]

A conditional allele of Prmt5 in the mouse limb shows that it is essential for maintaining a progenitor population, as conditional mutants have limb defects [20]

Protein arginine methyltransferase 5 has been shown to interact with:

• CLNS1A,[21][22][23][24]
• Janus kinase 2,[25]
• SNRPD3,[23]
• SUPT5H,[26]
• MEP50,[21]
• RIOK1, [27][24]
• COPR5.[24]

PRMT5 has been shown to interact with CLNS1A, RIOK1 and COPR5 through an interface created by a shallow groove located on the TIM barrel domain of PRMT5 and the consensus sequence GQF[D/E]DA[E/D] located in the terminal regions of the adaptor proteins.[24][28] The characterisation of the interactions occurring in the binding groove between PRMT5 and peptides derived from the adaptor proteins lead to development of protein-protein interaction (PPI) inhibitors, modulating binding between PRMT5 and the adaptor proteins.[29][30] Furthermore, Asberry and co-workers synthesised the first-in-class small molecule inhibitor of the PPI between PRMT5 and MEP50.[31] The PPI inhibitors complement a plethora of compounds directly suppressing the enzymatic activity of PRMT5.[32]