Structure and Function of Protein Arginine Methyltransferase PRMT7

Abstract

PRMT7 is a member of the protein arginine methyltransferase (PRMT) family, which methylates a diverse set of substrates. Arginine methylation as a posttranslational modification regulates protein–protein and protein–nucleic acid interactions, and as such, has been implicated in various biological functions. PRMT7 is a unique, evolutionarily conserved PRMT family member that catalyzes the mono-methylation of arginine. The structural features, functional aspects, and compounds that inhibit PRMT7 are discussed here. Several studies have identified physiological substrates of PRMT7 and investigated the substrate methylation outcomes which link PRMT7 activity to the stress response and RNA biology. PRMT7-driven substrate methylation further leads to the biological outcomes of gene expression regulation, cell stemness, stress response, and cancer-associated phenotypes such as cell migration. Furthermore, organismal level phenotypes of PRMT7 deficiency have uncovered roles in muscle cell physiology, B cell biology, immunity, and brain function. This rapidly growing information on PRMT7 function indicates the critical nature of context-dependent functions of PRMT7 and necessitates further investigation of the PRMT7 interaction partners and factors that control PRMT7 expression and levels. Thus, PRMT7 is an important cellular regulator of arginine methylation in health and disease.

Human protein arginine methyltransferases (PRMTs) can be optimally active under nonphysiological conditions

“…This is particularly a problem for PRMT7, whose activity appears to be generally low in comparison with the major type I PRMT1 enzyme or the major type II PRMT5 enzyme ( 5 , 35 ). Although evidence has been presented for a number of in vivo sites of PRMT7 methylation ( 7 , 10 , 36 , 37 , 38 ), it is not clear so far that these are specifically modified by PRMT7 alone and are not also sites for methylation by other PRMTs ( 39 ). Additionally, PRMT7 methylation of Arg-17 of a histone H4 peptide has been shown to allosterically activate PRMT5 methylation at the distinct Arg-3 site ( 9 ).…”

“…These modifications create distinct interactions between proteins and play a significant role in biology including transcription of DNA, activation of enzyme activity, and protein degradation ( 1 , 2 , 3 , 4 ). In mammals, nine specific enzymes (protein arginine methyltransferases [PRMTs]) have been characterized and are classified based on the specific reaction they catalyze ( 5 , 6 , 7 ). While all PRMTs can initially catalyze monomethylarginine formation, type I PRMTs (PRMT1, 2, 3, 4, 6, and 8) catalyze asymmetric dimethylarginine formation and type II PRMTs (PRMT 5 and 9) catalyze symmetric dimethylarginine formation, while type III PRMTs (PRMT7) only catalyzes monomethylarginine formation.…”

Targeting Arginine Methyltransferase PRMT5 for Cancer Therapy: Updated Progress and Novel Strategies

“…Human PRMT family members share a conserved SAM-dependent methyltransferase domain comprising the SAM- and substrate-binding pockets . However, outside the methyltransferase domain, human PRMT family members contain different motif structure. , PRMT1 and PRMT6 only possess the catalytic methyltransferase domain, − whereas PRMT2–5, PRMT8, and PRMT9 all have an N-terminal motif preceding the catalytic domain. − Although PRMT7 and PRMT9 both harbor a duplicated methyltransferase domain, the C-terminal domain in PRMT9 is well-known as a pseudodomain. − Type I PRMTs share a mutually higher sequence homology, and PRMT9 is closer to type I in the primary sequence, while PRMT5 and PRMT7 are the most distant family members and are also quite unique.…”

Knockdown of PRMT1 suppresses the malignant biological behavior of osteosarcoma cells and increases cisplatin sensitivity via c‐Myc‐mediated BCAT1 downregulation

“…PRMT7 is categorized as type III and only can catalyze MMA. [11] Specifically, PRMT1 belongs to a type I PRMT and is the most abundant PRMT that participates in arginine methylation in nearly 75% of cells. [12,13] PRMT1 can catalyze protein substrates containing glycine-arginine-rich motifs.…”