The Role of Protein Arginine Methylation as a Post-Translational Modification in Cellular Homeostasis and Disease
Simple Summary
Abstract
1. Introduction
2. Type I Protein Arginine Methyltransferase
2.1. PRMT1
Cancer Type | Role(s) in Cancer | Mechanism of Action | Ref. |
---|---|---|---|
Acute myelogenous leukemia | Cell transformation | PRMT1 + KDM4C→epigenetic reprogramming↑→AML cell transformation↑ | [28] |
Cell survival and proliferation | PRMT1→methylation of FLT3→survival and proliferation of FLT3-ITD AML cell↑ | [29] | |
Breast cancer | Cell proliferation/viability and cell cycle progression | PRMT1→methylation of ERα→interacts with Src/FAK and p85→cell proliferation and survival | |
PRMT1→EZH2 methylation→inhibits P16 and P21 transcriptional expression→promotes cell cycle progression | [30] | ||
Colorectal cancer | Promotion of glycolysis, proliferation, and tumorigenesis | PRMT1→meR206-PGK1→pS203-PGK1↑→glycolytic activity and CRC tumorigenesis | [31] |
Cell proliferative, colony-formative, and migratory abilities | PRMT1→H4R3me2a→recruits SMARCA4→EGFR signaling↑→proliferative, colony-formative, and migratory abilities↑ | [32] | |
Gastric cancer | Cell migration and metastasis | PRMT1→ recruits MLXIP→β-catenin transcription and the β-catenin signaling pathway↑→GC cell migration and metastasis | [33] |
Hepatocellular carcinoma | Cell proliferation and xenograft tumor growth | CDK5→phosphorylation of PRMT1→methylation of WDR24→mTORC1 pathway↑ | [34] |
Human melanoma | Tumor growth and metastasis | PRMT1→methylation of ALCAM→tumor growth and metastasis | [35] |
Lung cancer | DNA repair ability and chemotherapeutic drug resistance | PRMT1→methylation of FEN1→DNA repair ability and drug resistance | [36] |
Cell invasion and drug resistance | PRMT1→methylation of Twist1 and p120-catenin expression↑→transcription of Kaiso↑→EMT in Osimertinib-resistant cells↑ | [37] | |
Multiple myeloma | Cell proliferation and apoptosis | PRMT1→methylation of WTAP→NDUFS6 m6A modification →MM cell proliferation and OCR levels ↑ cell apoptosis and ROS levels↓ | [38] |
Ovarian cancer | Cell migration and invasion | PRMT1→Methylation of BRD4→phosphorylation of BRD4→migration and invasion | [39] |
Pancreatic cancer | Apoptosis | stress response →PRMT1→methylation of p14ARF→p53—independent apoptosis | [40] |
Prostate cancer | PCa cell growth | PRMT1 + circ_0094606→methylation of ILF3→stability of IL-8 mRNA↑→M2 polarization of macrophages→PCa growth↑ | [41] |
2.2. PRMT2
2.3. PRMT3
2.4. PRMT4 (CARM1)
2.5. PRMT6
2.6. PRMT8
3. Type II Protein Arginine Methyltransferase
3.1. PRMT5
Cancer Type | Role(s) in Cancer | Mechanism of Action | Ref. |
---|---|---|---|
Breast cancer | Inhibition of ferroptosis of breast cancer cells | PRMT5→KEAP1/R596me2→KEAP1 ubiquitination (by TRIM25)↓→NRF2/HMOX1 expression↓→ ferroptosis of TNBC cells↓ | [129] |
Attenuation of autophagy | PRMT5→methylation of ULK1→kinase activity and basal autophagic function↓ | [131] | |
Inhibition of cell proliferation | tamoxifen→PRMT5→methylation of Erα→transcription and cell proliferation↓ | [132] | |
Cervical cancer | Promotion of cancer progression | PRMT5→H3R2me2s→transcription of STAT1↑→PD-L1 expression↑→development of cervical cancer↑ | [130] |
Chronic lymphocytic leukemia | Promotion of cancer progression | PRMT5→activates oncogenic signaling pathways→CLL development↑→Richter’s transformation | [133] |
Colorectal cancer | Promotion of cancer cell dissemination | PRMT5→ methylation of SMAD4→activation of TGF-β signaling→promotion of CRC dissemination | [134] |
Promotion of cell proliferation, migration and invasion | PRMT5 interacts with MCM7→cell proliferation, migration, and invasion ↑ | [135] | |
cell proliferation | PRMT5→H3R8Me2s→activates LDHA→glycolysis↑→cell proliferation | [136] | |
Promotion of CRC development | PRMT5 and EZH2→H3K27me3, H4R3me2s and H3R8me2s→CDKN2B (p15INK4b) expression↓→promotes CRC development | [137] | |
Glioma | Malignant phenotype | PRMT5→ERK1/2 pathway→malignant phenotype of glioma cells↑ | [138] |
Promotion of self-renewal and proliferation | PRMT5→PTEN–AKT axis→GBM neurosphere self-renewal and proliferation↑ | [139] | |
Hepatocellular carcinoma | Activation of de novo lipogenesis and tumorigenesis | PRMT5→methylation of SREBP1a→activates de novo lipogenesis and tumorigenesis | [140] |
Liver cancer | Cell proliferation | PRMT5→ERK signaling→BTG2 expression↓→liver cancer cell proliferation | [141] |
Lung cancer | Cell proliferation | PRMT5→methylation of KLF5→inhibit KLF5 degradation→promotes the maintenance and proliferation of lung cancer cells | [142] |
Growth inhibition | PRMT5 inhibition + anti-PD-L1→inhibits the growth of lung cancer cells and activates CD8+ T cell immune surveillance | [143] | |
Cell proliferation and metastasis | PRMT5→activation of the FGFR3/Akt signaling axis→lung cancer cell proliferation and metastasis | [144] | |
Lymphoma | Cell survival | PRMT5→promotes WNT/β-CATENIN and AKT/GSK3β proliferative signaling→survival of lymphoma cells↑ | [145] |
Ovarian cancer | Tumor growth | PRMT5→methylation of ENO1→promotes active ENO1 dimer formation→glycolysis flux↑→tumor growth↑ | [146] |
Pancreatic cancer | Aerobic glycolysis and cell proliferation | PRMT5→expression of the tumor suppressor FBW7↓→stabilization of cMyc↑→aerobic glycolysis and pancreatic cancer cell proliferation↑ | [125] |
Promotion of EMT | PRMT5→autophosphorylation of EGFR (Y1068 and Y1172)↑→activates Akt--β--catenin axis→promotes EMT | [147] | |
Prostate cancer | Promotion of cancer progression | circSPON2/miR-331-3p axis→PRMT5→H4R3me2s and H3R8me2s→CAMK2N1↓→PCa progression↑ | [148] |
Cell growth | PRMT5 + Sp1 + Brg1→H4R3me2s→activates transcription of AR→prostate cancer cell growth↑ | [149] |
3.2. PRMT9
4. Type III Protein Arginine Methyltransferase
PRMT7
PRMT Isoform | Knockout Type | Model Description | Viability/Lethality | Key Tissue/Cellular Phenotypes | Ref. |
---|---|---|---|---|---|
PRMT1 | Conventional Homozygous KO | Gene trap | Embryotoxicity | [16] | |
Conditional Homozygous KO | ERT2-Cre; endothelial cell-specific knockout | Viability | Worsening of pulmonary hemorrhage | [176] | |
Conditional Homozygous KO | Mx1-Cre; adult hematopoietic cell-specific knockout | About one in eight mice died within five months | Prominent effect on adult hematopoiesis | [177] | |
Conditional Homozygous KO | Ngn3-Cre; germ cell-specific knockout | Viability | Prmt1 KO male mice were completely infertile; female KO mice were fertile | [178] | |
Conditional Homozygous KO | Vil-CreERT2; intestinal epithelium-specific knockout | Viability | Intestinal cell proliferation and crypt elongation increased in mice aged 8–12 weeks | [179] | |
Conditional Homozygous KO | Myh6-cre; myocardium-specific knockout | Mouse lethality began at four weeks of age and nearly all died within two months | [180] | ||
Conditional Heterozygous KO | Myh6-cre; myocardium-specific knockout | 25 percent of mice were dead within two months | [180] | ||
Conditional Heterozygous KO | Myl1-Cre; skeletal muscle-specific knockout | Viability | Muscle loss | [181] | |
Conventional Homozygous KO | Cre/loxP recombination system | Embryos did not survive to 7.5 days | [17] | ||
Conditional Homozygous KO | Cre/loxP recombination system; epidermis-specific knockout | Small body size, thin clinical epidermis, and perinatal mortality | [182] | ||
Conditional Homozygous KO | Flp-Cre; hepatocyte-specific knockout | Viability | [183] | ||
PRMT2 | Conventional Homozygous KO | Standard gene targeting | Viability | There is no obvious difference in the display form | [45] |
PRMT3 | Conventional Homozygous KO | Standard gene targeting | Viability; mouse embryos targeted to disrupt PRMT3 were smaller but survived after birth and reached normal mouse size as adults | [57] | |
Conditional Homozygous KO | Alb-Cre; liver-specific knockout | Viability | Inhibited tumor progression and increased CD8+ T cell infiltration in mouse tumors | [184] | |
CARM1 | Conventional Homozygous KO | Standard gene targeting | Mouse embryos survived to birth and responded to stimuli but developed respiratory distress and died within 20 min | [185] | |
PRMT5 | Conditional Homozygous KO | MyoDCre; myogenic lineage-specific knockout | Adult mice died prematurely | Muscle atrophy and early death | [186] |
Conditional Homozygous KO | Cre-loxP; medullary thymic epithelial cell-specific knockout | Viability | Smaller thymus in mice | [187] | |
Conditional Homozygous KO | Myl1-CRE; skeletal muscle-specific knockout | Viability | Muscle mass, oxidative capacity, power generation, and exercise performance decreased in mice | [188] | |
Conditional Homozygous KO | Pdx 1-CreER; islet-specific knockout | Viability | Decreased glucose tolerance in mice | [189] | |
Conditional Homozygous KO | OC-Cre; osteoblast-specific knockout | Viability | Delayed socket healing in Prmt5 knockout mice | [190] | |
Conventional Homozygous KO | Mx1-Cre | Two weeks after the first induction, the mice developed severe anemic pallor, and most of the mice with PRMT5 deficiency died within 1–2 days | Deletion of PRMT5 during adult hematopoiesis leads to severe cytopenias | [191] | |
PRMT6 | Conventional Homozygous KO | CRISPR-Cas9 | Viability | Enhanced the body’s innate antiviral immunity | [87] |
Conventional Homozygous KO | EIIa-Cre | Viability | [192] | ||
PRMT7 | Conditional Homozygous KO | Cdh5-CreERT2; endothelial cell-specific knockout | Viability | Increased apoptosis and fibrosis impair heart recovery | [193] |
Conventional Homozygous KO | Standard gene targeting | Viability | Muscles show a shift to glycolytic fiber types | [166] | |
Conditional Homozygous KO | Myh6-Cre; cardiac-specific knockout | Viability; birth rate decreased by about half | Plays a protective role in Ang II-induced cardiomyopathy | [194] | |
PRMT8 | Conventional Homozygous KO | Ayu1-Cre | Viability | Acetylcholine and choline decreased while PC levels increased | [95] |
Conventional Homozygous KO | Standard gene targeting | Viability | In mice, the composition of phospholipids was changed, mitochondrial stress capacity was reduced, and neuroinflammatory markers were increased | [98] | |
PRMT9 | Conventional Homozygous KO | CMV-Cre | Some died after birth | Sea horse neurons showed impaired excitatory synapse development | [195] |
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Li, K.; Xia, Q.; Li, K.; Yan, W.; Wang, C. The Role of Protein Arginine Methylation as a Post-Translational Modification in Cellular Homeostasis and Disease. Biology 2025, 14, 1370. https://doi.org/10.3390/biology14101370
Li K, Xia Q, Li K, Yan W, Wang C. The Role of Protein Arginine Methylation as a Post-Translational Modification in Cellular Homeostasis and Disease. Biology. 2025; 14(10):1370. https://doi.org/10.3390/biology14101370
Chicago/Turabian StyleLi, Ke, Qing Xia, Kexin Li, Wenxin Yan, and Changshan Wang. 2025. "The Role of Protein Arginine Methylation as a Post-Translational Modification in Cellular Homeostasis and Disease" Biology 14, no. 10: 1370. https://doi.org/10.3390/biology14101370
APA StyleLi, K., Xia, Q., Li, K., Yan, W., & Wang, C. (2025). The Role of Protein Arginine Methylation as a Post-Translational Modification in Cellular Homeostasis and Disease. Biology, 14(10), 1370. https://doi.org/10.3390/biology14101370