PRMT1 explained

Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene.^[1] The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.^[2]

Function

PRMT1 gene encodes for the protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4 in eukaryotic cells.^[3] Specifically altering histone H4 in eukaryotes gives it the ability to remodel chromatin acting as a post-translational modifier.

Through regulation of gene expression, arginine methyltransferases control the cell cycle and death of eukaryotic cells.^[4]

Reaction pathway

While all PRMT enzymes catalyze the methylation of arginine residues in proteins, PRMT1 is unique in that is catalyzes the formation of asymmetric dimethylarginine as opposed to the PRMT2 that catalyzes the formation of symmetrically dimethylated arginine.^[5] Individual PRMT utilize S-adenosyl-L-methionine (SAM) as the methyl donor and catalyze methyl group transfer to the ω-nitrogen of an arginine residue.

Clinical significance

In humans, these enzymes regulate gene expression and hence are involved in pathogenesis of many human diseases.^[6] Using enzyme inhibitors for arginine methyltransferase 1, studies were able to demonstrate the enzyme's potential as an early catalyst of various cancers.^[7]

Interactions

PRMT1 has been shown to interact with:

• BTG1,
• BTG2,^{[8] [9]}
• DHX9,^[10]
• FUS,
• HNRNPR,^[11]
• HNRPK,^[12]
• IFNAR1,^[13]
• ILF3,^{[14] [15]}
• KHDRBS1,^[16] and
• SUPT5H.^[17]

Further reading

• Kim S, Park GH, Paik WK . Recent advances in protein methylation: enzymatic methylation of nucleic acid binding proteins . Amino Acids . 15 . 4 . 291–306 . 1999 . 9891755 . 10.1007/BF01320895 . 28412209 .
• Baldwin GS, Carnegie PR . Specific enzymic methylation of an arginine in the experimental allergic encephalomyelitis protein from human myelin . Science . 171 . 3971 . 579–81 . 1971 . 4924231 . 10.1126/science.171.3971.579 . 1971Sci...171..579B . 36959912 .
• Rajpurohit R, Lee SO, Park JO, Paik WK, Kim S . Enzymatic methylation of recombinant heterogeneous nuclear RNP protein A1. Dual substrate specificity for S-adenosylmethionine:histone-arginine N-methyltransferase . J. Biol. Chem. . 269 . 2 . 1075–82 . 1994 . 10.1016/S0021-9258(17)42223-X . 8288564 . free .
• Lin WJ, Gary JD, Yang MC, Clarke S, Herschman HR . The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase . J. Biol. Chem. . 271 . 25 . 15034–44 . 1996 . 8663146 . 10.1074/jbc.271.25.15034 . free .
• Nikawa J, Nakano H, Ohi N . Structural and functional conservation of human and yeast HCP1 genes which can suppress the growth defect of the Saccharomyces cerevisiae ire15 mutant . Gene . 171 . 1 . 107–11 . 1996 . 8675017 . 10.1016/0378-1119(96)00073-X .
• Abramovich C, Yakobson B, Chebath J, Revel M . A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor . EMBO J. . 16 . 2 . 260–6 . 1997 . 9029147 . 1169633 . 10.1093/emboj/16.2.260 .
• Klein S, Carroll JA, Chen Y, Henry MF, Henry PA, Ortonowski IE, Pintucci G, Beavis RC, Burgess WH, Rifkin DB . Biochemical analysis of the arginine methylation of high molecular weight fibroblast growth factor-2 . J. Biol. Chem. . 275 . 5 . 3150–7 . 2000 . 10652299 . 10.1074/jbc.275.5.3150 . free .
• Tang J, Kao PN, Herschman HR . Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3 . J. Biol. Chem. . 275 . 26 . 19866–76 . 2000 . 10749851 . 10.1074/jbc.M000023200 . free .
• Nichols RC, Wang XW, Tang J, Hamilton BJ, High FA, Herschman HR, Rigby WF . The RGG domain in hnRNP A2 affects subcellular localization . Exp. Cell Res. . 256 . 2 . 522–32 . 2000 . 10772824 . 10.1006/excr.2000.4827 .
• Zhang X, Zhou L, Cheng X . Crystal structure of the conserved core of protein arginine methyltransferase PRMT3 . EMBO J. . 19 . 14 . 3509–19 . 2000 . 10899106 . 313989 . 10.1093/emboj/19.14.3509 .
• Koh SS, Chen D, Lee YH, Stallcup MR . Synergistic enhancement of nuclear receptor function by p160 coactivators and two coactivators with protein methyltransferase activities . J. Biol. Chem. . 276 . 2 . 1089–98 . 2001 . 11050077 . 10.1074/jbc.M004228200 . free .
• Scorilas A, Black MH, Talieri M, Diamandis EP . Genomic organization, physical mapping, and expression analysis of the human protein arginine methyltransferase 1 gene . Biochem. Biophys. Res. Commun. . 278 . 2 . 349–59 . 2001 . 11097842 . 10.1006/bbrc.2000.3807 .
• Rho J, Choi S, Seong YR, Cho WK, Kim SH, Im DS . Prmt5, which forms distinct homo-oligomers, is a member of the protein-arginine methyltransferase family . J. Biol. Chem. . 276 . 14 . 11393–401 . 2001 . 11152681 . 10.1074/jbc.M008660200 . free .
• Mowen KA, Tang J, Zhu W, Schurter BT, Shuai K, Herschman HR, David M . Arginine methylation of STAT1 modulates IFNalpha/beta-induced transcription . Cell . 104 . 5 . 731–41 . 2001 . 11257227 . 10.1016/S0092-8674(01)00269-0 . 17584895 . free .
• Wang H, Huang ZQ, Xia L, Feng Q, Erdjument-Bromage H, Strahl BD, Briggs SD, Allis CD, Wong J, Tempst P, Zhang Y . Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor . Science . 293 . 5531 . 853–7 . 2001 . 11387442 . 10.1126/science.1060781 . 33566292 . free .
• Strahl BD, Briggs SD, Brame CJ, Caldwell JA, Koh SS, Ma H, Cook RG, Shabanowitz J, Hunt DF, Stallcup MR, Allis CD . Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1 . Curr. Biol. . 11 . 12 . 996–1000 . 2001 . 11448779 . 10.1016/S0960-9822(01)00294-9 . 17783289 . free . 2001CBio...11..996S .
• Rho J, Choi S, Seong YR, Choi J, Im DS . The Arginine-1493 Residue in QRRGRTGR1493G Motif IV of the Hepatitis C Virus NS3 Helicase Domain Is Essential for NS3 Protein Methylation by the Protein Arginine Methyltransferase 1 . J. Virol. . 75 . 17 . 8031–44 . 2001 . 11483748 . 115047 . 10.1128/JVI.75.17.8031-8044.2001 .
• Lee J, Bedford MT . PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays . EMBO Rep. . 3 . 3 . 268–73 . 2002 . 11850402 . 1084016 . 10.1093/embo-reports/kvf052 .

Notes and References

1. Scott HS, Antonarakis SE, Lalioti MD, Rossier C, Silver PA, Henry MF . Identification and characterization of two putative human arginine methyltransferases (HRMT1L1 and HRMT1L2) . Genomics . 48 . 3 . 330–40 . June 1998 . 9545638 . 10.1006/geno.1997.5190 .
2. Web site: Entrez Gene: PRMT1 protein arginine methyltransferase 1.
3. Web site: Entrez Gene: PRMT1 protein arginine methyltransferase 1.
4. Book: Qian K, Zhen G . Chapter 8 - Current Development of Protein Arginine Methyltransferase Inhibitors. 2016-01-01 . Epi-Informatics. 231–256. Medina-Franco JL . Boston. Academic Press. en. 10.1016/b978-0-12-802808-7.00008-3. 978-0-12-802808-7 .
5. Obianyo O, Osborne TC, Thompson PR . Kinetic mechanism of protein arginine methyltransferase 1 . Biochemistry . 47 . 39 . 10420–7 . September 2008 . 18771293 . 2933744 . 10.1021/bi800904m .
6. Book: Zeng H, Xu W . Chapter 16 - Enzymatic Assays of Histone Methyltransferase Enzymes. 2015-01-01 . Epigenetic Technological Applications. 333–361. Zheng YG . Boston. Academic Press . 10.1016/b978-0-12-801080-8.00016-8. 978-0-12-801080-8 .
7. Carbone F, Montecucco F, Xu S, Banach M, Jamialahmadi T, Sahebkar A . Epigenetics in atherosclerosis: key features and therapeutic implications . Expert Opinion on Therapeutic Targets . 24 . 8 . 719–721 . August 2020 . 32354276 . 10.1080/14728222.2020.1764535 . free .
8. Lin WJ, Gary JD, Yang MC, Clarke S, Herschman HR . The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase . J. Biol. Chem. . 271 . 25 . 15034–44 . June 1996 . 8663146 . 10.1074/jbc.271.25.15034. free .
9. Berthet C, Guéhenneux F, Revol V, Samarut C, Lukaszewicz A, Dehay C, Dumontet C, Magaud JP, Rouault JP . Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects . Genes Cells . 7 . 1 . 29–39 . January 2002 . 11856371 . 10.1046/j.1356-9597.2001.00497.x . 15016952 . free .
10. Smith WA, Schurter BT, Wong-Staal F, David M . Arginine methylation of RNA helicase a determines its subcellular localization . J. Biol. Chem. . 279 . 22 . 22795–8 . May 2004 . 15084609 . 10.1074/jbc.C300512200 . free .
11. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . September 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
12. Wada K, Inoue K, Hagiwara M . Identification of methylated proteins by protein arginine N-methyltransferase 1, PRMT1, with a new expression cloning strategy . Biochim. Biophys. Acta . 1591 . 1–3 . 1–10 . August 2002 . 12183049 . 10.1016/s0167-4889(02)00202-1 . free .
13. Abramovich C, Yakobson B, Chebath J, Revel M . A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor . EMBO J. . 16 . 2 . 260–6 . January 1997 . 9029147 . 1169633 . 10.1093/emboj/16.2.260 .
14. Lee J, Bedford MT . PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays . EMBO Rep. . 3 . 3 . 268–73 . March 2002 . 11850402 . 1084016 . 10.1093/embo-reports/kvf052 .
15. Tang J, Kao PN, Herschman HR . Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3 . J. Biol. Chem. . 275 . 26 . 19866–76 . June 2000 . 10749851 . 10.1074/jbc.M000023200 . free .
16. Côté J, Boisvert FM, Boulanger MC, Bedford MT, Richard S . Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1 . Mol. Biol. Cell . 14 . 1 . 274–87 . January 2003 . 12529443 . 140244 . 10.1091/mbc.E02-08-0484 .
17. Richard Gaynor. Kwak YT, Guo J, Prajapati S, Park KJ, Surabhi RM, Miller B, Gehrig P, Gaynor RB . Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties . Mol. Cell . 11 . 4 . 1055–66 . April 2003 . 12718890 . 10.1016/s1097-2765(03)00101-1 . free .