PRMT7 as a unique member of the protein arginine methyltransferase family: A review

Abstract

Protein arginine methyltransferases (PRMTs) are found in a wide variety of eukaryotic organisms and can regulate gene expression, DNA repair, RNA splicing, and stem cell biology. In mammalian cells, nine genes encode a family of sequence-related enzymes; six of these PRMTs catalyze the formation of ω-asymmetric dimethyl derivatives, two catalyze ω-symmetric dimethyl derivatives, and only one (PRMT7) solely catalyzes ω-monomethylarginine formation. Purified recombinant PRMT7 displays a number of unique enzymatic properties including a substrate preference for arginine residues in R-X-R motifs with additional flanking basic amino acid residues and a temperature optimum well below 37 °C. Evidence has been presented for crosstalk between PRMT7 and PRMT5, where methylation of a histone H4 peptide at R17, a PRMT7 substrate, may activate PRMT5 for methylation of R3. Defects in muscle stem cells (satellite cells) and immune cells are found in mouse Prmt7 homozygous knockouts, while humans lacking PRMT7 are characterized by significant intellectual developmental delays, hypotonia, and facial dysmorphisms. The overexpression of the PRMT7 gene has been correlated with cancer metastasis in humans. Current research challenges include identifying cellular factors that control PRMT7 expression and activity, identifying the physiological substrates of PRMT7, and determining the effect of methylation on these substrates.

RETRACTED: Arginine methylation of SHANK2 by PRMT7 promotes human breast cancer metastasis through activating endosomal FAK signalling

“…Protein arginine methyltransferases (PRMTs) catalyze mono-methylation and symmetric or asymmetric di-methylation of arginine residues on both histone and non-histone substrates to modulate diverse biological processes, including transcription, cell signalling, mRNA translation, DNA damage repair signalling, receptor trafficking, protein stability and pre-mRNA splicing ( Jelinic et al, 2006 ; Bedford and Clarke, 2009 ; Dhar et al, 2012 ; Jeong et al, 2016 ; Blanc and Richard, 2017 ; Jeong et al, 2020 ). Protein Arginine Methyltransferase 7 (PRMT7) was reported as a type III PRMT to catalyze mono-methylation of arginine residues on both histone and non-histone substrates ( Bedford and Clarke, 2009 ; Karkhanis et al, 2012 ; Blanc and Richard, 2017 ; Jain and Clarke, 2019 ; Haghandish et al, 2019 ). Recent studies also reported that PRMT7 can symmetrically di-methylate proteins such as p38 and GLI2 ( Jeong et al, 2020 ; Vuong et al, 2020 ).…”

Identification, expression and functional analysis of prmt7 in medaka Oryzias latipes

“…The reason may be that the three motifs in the N terminal catalytic domain are very important for the enzymatic activity. Dot mutations in these motifs have been reported to change the enzyme activity (Cáceres et al, 2018; Debler et al, 2016; Feng, Hadjikyriacou, & Clarke, 2014; Hasegawa et al, 2014; Jain & Clarke, 2019). These results suggest that medaka Prmt7 may play similar roles with the PRMT7 in other species.…”

“…In human, it was also found that two male sibs with a homozygous PRMT7 mutation presented with an early intrauterine growth restriction. The patients with PRMT7 mutations showed sensorineural hearing loss, severe intellectual disability, genitourinary involvement, and global developmental delay after birth (Birnbaum et al, 2019;Jain & Clarke, 2019). In Xenopus, prmt7…”

“…PRMT7 is the only type III PRMT and catalyzes methylation of several R sites in histones (Hadjikyriacou & Clarke, 2017; Karkhanis et al, 2012; Migliori et al, 2012). PRMT7 has been reported to be involved in a variety of cellular processes in mammals (Jain & Clarke, 2019). PRMT7 played a role in male germline‐imprinted gene methylation through its interaction with the epigenetic regulator CFCFL (Jelinic, Stehle, & Shaw, 2006).…”

Fine-Tuning of GLI Activity Through Arginine Methylation: Its Mechanisms and Function

“…The type III PRMT (PRMT7) catalyzes only the monomethyl arginine of specific arginine residues. Arginine methylation by PRMTs is involved in gene transcription, pre-mRNA splicing, signal transduction, DNA damage response, and cell fate decisions [33][34][35].…”