| 1999 |
Human PRMT5 (JBP1/SKB1Hs) is a protein methyltransferase that can be cross-linked to radiolabeled S-adenosylmethionine (AdoMet) and methylates histones H2A and H4 as well as myelin basic protein in vitro. Conserved motifs implicated in AdoMet binding are required for activity, as substitution mutants in this region show little or no methyltransferase activity. PRMT5 co-immunoprecipitates with Jak2 and several other proteins that serve as methyl-group acceptors. |
AdoMet cross-linking, in vitro methyltransferase assay, active-site mutagenesis, co-immunoprecipitation, yeast two-hybrid |
The Journal of biological chemistry |
High |
10531356
|
| 1998 |
The human homolog SKB1Hs can functionally replace fission yeast Skb1 in S. pombe, indicating evolutionary conservation of function. Fission yeast Skb1 negatively regulates mitosis by a mechanism independent of Cdc25 but at least partially dependent on Shk1 and Wee1; Skb1 and Shk1 biochemically associate with Cdc2 in S. pombe, suggesting inhibition of mitosis through interaction with the Cdc2 complex. |
Genetic complementation, genetic epistasis, biochemical co-immunoprecipitation with Cdc2 |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
9843966
|
| 1996 |
Fission yeast Skb1 (ortholog of human PRMT5) interacts with Shk1 (PAK homolog) via the N-terminal regulatory domain of Shk1 at a site distinct from the Cdc42-binding region; Skb1, Shk1 and Cdc42 can form a ternary complex in vivo. Skb1 positively modulates Shk1 function and acts as a component of the morphology-control branch of the Ras signaling cascade. |
Yeast two-hybrid, in vivo co-immunoprecipitation (ternary complex), genetic epistasis |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
8943016
|
| 2001 |
Fission yeast Skb1 localizes to cell ends, sites of septation, and nuclei; hyperosmotic shock causes delocalization from cell ends and nuclei and stimulates Skb1 protein methyltransferase activity. The methyltransferase activity of the human homolog Skb1Hs is similarly stimulated by hyperosmotic stress in fission yeast, indicating evolutionary conservation of the stress-responsive activity regulation. |
Subcellular localization by fluorescence microscopy, in vitro methyltransferase activity assay under osmotic stress, functional complementation in yeast |
The Journal of biological chemistry |
Medium |
11278267
|
| 2016 |
Loss of MTAP leads to intracellular accumulation of methylthioadenosine (MTA), which specifically and potently inhibits PRMT5 enzymatic activity. MTAP-null cells therefore display a hypomorphic PRMT5 state and selective dependence on PRMT5 and its binding partner WDR77. Reconstitution of MTAP in MTAP-deficient cells rescues PRMT5 dependence. |
Metabolomic profiling, biochemical methyltransferase inhibition assays (MTA vs. PRMT5), shRNA screening across 390 cancer cell lines, isogenic cell line rescue experiments |
Science (New York, N.Y.) |
High |
26912360 26912361 27068473
|
| 2016 |
MTA is a potent and selective inhibitor of PRMT5 among a panel of methyltransferases. MAT2A, which produces the PRMT5 substrate SAM, is also a synthetic lethal target in MTAP-deleted cells because MAT2A depletion reduces SAM levels and further attenuates PRMT5 methylation activity. RIOK1, a PRMT5 co-complex protein, is also a vulnerability in MTAP-deleted cells. |
Biochemical methyltransferase enzyme panel profiling, metabolomic studies, shRNA screening, co-complex identification |
Cell reports |
High |
27068473
|
| 2017 |
The PRMT5:MEP50 complex forms a 453 kDa heterooctamer. Crystal structures of this complex bound to an S-adenosylmethionine analog and a substrate peptide reveal the mechanism of substrate recognition and procession to dimethylation. |
Crystal structure determination of human PRMT5:MEP50 complex with SAM analog and substrate peptide |
Sub-cellular biochemistry |
High |
28271477
|
| 2018 |
LKB1 directly interacts with and phosphorylates PRMT5 at T132, T139 and T144 residues in its TIM-barrel domain. Point mutations T139A/T144A drastically reduce PRMT5 methyltransferase activity, likely by disrupting interaction with regulatory cofactors MEP50, pICln and RiOK1. Modulation of LKB1 expression alters PRMT5 activity. |
Co-immunoprecipitation, in vitro kinase assay identifying phosphorylation sites, point mutagenesis of PRMT5, methyltransferase activity assay |
International journal of cancer |
Medium |
30289978
|
| 2019 |
PRMT5 functions in complex with MEP50/WDR77 and is responsible for the vast majority of symmetric dimethylarginine in cells. A CRISPR/Cas9 screen identified PRMT5, MEP50/WDR77, PPP4C, SMNDC1, and SRSF3 as components of the PRMT5 writer/reader pathway. Loss of PRMT1 (the major asymmetric arginine methyltransferase) also sensitizes cells to PRMT5 inhibition, demonstrating partial redundancy between the PRMT5 and PRMT1 pathways. |
CRISPR/Cas9 genetic screen, combinatorial inhibitor treatment, genetic epistasis |
Nucleic acids research |
Medium |
30916320
|
| 2020 |
PRMT5 is phosphorylated at residue Y324 by Src kinase, which suppresses PRMT5 activity by preventing its binding to the methyl donor S-adenosyl-L-methionine. PRMT5 activity promotes non-homologous end joining (NHEJ) DNA repair by methylating and stabilizing 53BP1; Src-mediated phosphorylation of PRMT5 during DNA damage inhibits NHEJ and promotes apoptosis. |
Site-specific phosphorylation assay, mutagenesis of Y324, SAM-binding assay, co-immunoprecipitation of PRMT5 with 53BP1, NHEJ repair assays, cell survival after DNA damage |
Communications biology |
Medium |
32759981
|
| 2020 |
PRMT5 methylation of IFI16/IFI204 (components of the cGAS/STING pathway) attenuates cytosolic DNA-induced IFN and chemokine expression in melanoma cells. PRMT5 also inhibits NLRC5 transcription, reducing MHC class I antigen presentation. PRMT5 knockdown augments IFN and chemokine production and increases MHC class I abundance. |
PRMT5 knockdown (shRNA), pharmacological inhibition (GSK3326595), measurement of IFN/chemokine production, NLRC5 and MHCI expression, immunocompetent vs immunocompromised mouse models |
Science translational medicine |
Medium |
32641491
|
| 2021 |
PRMT5 promotes AKT1 activation by catalyzing symmetric dimethylation of AKT1 at arginine 391 (R391). R391 methylation cooperates with PIP3 to relieve the PH-in conformation of AKT1, enabling its translocation to the plasma membrane and subsequent activation by PDK1 and mTORC2. Deficiency in AKT1-R391 methylation significantly suppresses AKT1 kinase activity and tumorigenesis. |
In vitro methylation assay, mutagenesis of AKT1-R391, AKT1 membrane translocation assay, kinase activity assay, co-immunoprecipitation with PDK1/mTORC2, xenograft tumor models |
Nature communications |
High |
34103528 35803962
|
| 2021 |
PRMT5 uses modular adaptor proteins (CLNS1A/pICln, RIOK1, and COPR5) for substrate recruitment through an evolutionarily conserved peptide motif shared among all three adaptors. This motif is necessary and sufficient for interaction with PRMT5. Disruption of the PRMT5-adaptor interface impairs methylation of adaptor-recruited substrates including spliceosome Sm proteins, histones, and ribosomal complexes, affects Sm spliceosome activity leading to intron retention, and impairs growth of MTAP-null tumor cells. |
Structural resolution of the PRMT5-adaptor interface, mutagenesis of the binding motif, methylation assays of adaptor-recruited substrates, RNA splicing assays, MTAP-null cell growth assays |
Molecular cell |
High |
34358446
|
| 2021 |
PRMT5 regulates the expression of the E3 ubiquitin ligase RNF168, thereby stabilizing H2AX. Suppression of PRMT5 (e.g., in MTAP-deficient cells) reduces RNF168 expression, leading to destabilization of H2AX by E3 ubiquitin ligase SMURF2, resulting in higher levels of spontaneous and genotoxic-agent-induced DNA damage. |
shRNA knockdown of PRMT5/RNF168/SMURF2, co-immunoprecipitation to show RNF168 and SMURF2 interactions with H2AX, H2AX stability assays, DNA damage measurement in MTAP-deficient glioblastoma cells |
Cell reports |
Medium |
31533041
|
| 2021 |
MAT2A inhibition reduces SAM levels, which attenuates PRMT5 activity, causing widespread splicing perturbations (particularly of cell cycle genes) and subsequent DNA damage and mitotic defects in MTAP-null cells. |
Potent MAT2A inhibitor characterization, RNA sequencing, proteomics, measurement of SAM levels, DNA damage and mitotic defect assays in HCT116 MTAP-/- cells |
Cancer cell |
High |
33450196
|
| 2021 |
PRMT5 inhibition causes widespread disruption of mRNA splicing across the transcriptome in glioblastoma, particularly affecting cell cycle gene products, consistent with its role in methylating spliceosome components. |
Pharmacological inhibition with two orthogonal PRMT5 inhibitors (GSK591 and LLY-283), RNA sequencing of 46 patient-derived GBM stem cell cultures, in vivo brain-penetrant inhibitor study |
Nature communications |
High |
33579912
|
| 2021 |
PRMT5 inhibition in GBM neurospheres causes G1 cell cycle arrest through upregulation of p27 and hypophosphorylation of retinoblastoma protein, leading to senescence. Chromatin immunoprecipitation revealed that PRMT5 regulates PTEN expression in GBM neurospheres via methylation, controlling Akt and ERK activity; PTEN is identified as a downstream target of PRMT5 in GBM neurospheres. |
shRNA knockdown, Human Phospho-Kinase Array, chromatin immunoprecipitation-PCR for PTEN promoter, cell cycle analysis, in vivo intracranial tumor model |
Oncogene |
Medium |
27292259
|
| 2018 |
PRMT5 methylates histone H4R3 (H4R3me2s) to catalyze symmetric methylation critical for oligodendrocyte differentiation and developmental myelination. Decreased H4R3me2s upon PRMT5 loss is followed by increased nuclear H4K5 acetylation; pharmacological inhibition of histone acetyltransferases rescues the differentiation defect, establishing a cross-talk between histone arginine methylation and lysine acetylation. |
Pharmacological inhibition, CRISPR/Cas9 knockout, conditional genetic ablation (Prmt5 conditional KO in progenitors), histone modification analysis with purified histones, differentiation/survival assays in oligodendrocyte progenitors and mice |
Nature communications |
High |
30026560
|
| 2021 |
Arginine methyltransferase PRMT5 directly binds cGAS and catalyzes symmetric dimethylation of cGAS at Arg124 (R124). This methylation attenuates cGAS-mediated antiviral immune response by blocking the DNA-binding ability of cGAS. |
Co-immunoprecipitation (PRMT5–cGAS interaction), in vitro methylation assay identifying R124, DNA-binding assay showing blockade, in vivo HSV-1 infection model with PRMT5 inhibitors |
Science advances |
Medium |
33762328
|
| 2022 |
PRMT5 inhibition in lung cancer reduces symmetric dimethylation of histone H4R3 (H4R3me2s) at the CD274 (PD-L1) promoter locus, thereby de-repressing CD274 gene expression and increasing PD-L1 on tumor cells, activating the PD1/PD-L1 axis and eliminating CD8+ T cell anti-tumor immunity. |
ChIP analysis of H4R3me2s at CD274 promoter, shRNA knockdown, PRMT5 inhibitor treatment, in vitro and in vivo measurement of PD-L1 expression |
Frontiers in immunology |
Medium |
35111150
|
| 2022 |
PRMT5 methylates KEAP1, downregulating NRF2 and its downstream targets. In TNBC with high ferrous levels, this PRMT5-mediated NRF2 suppression inhibits the HMOX1 pathway and promotes ferroptosis resistance by slowing ferrous import. |
Biochemical assays for KEAP1 methylation by PRMT5, co-IP, measurement of NRF2 targets and cellular ferrous levels, ferroptosis assays in TNBC vs non-TNBC cells |
Journal for immunotherapy of cancer |
Medium |
37380368
|
| 2022 |
PRMT5 promotes ALKBH5 nuclear translocation by methylating ALKBH5 at an arginine residue, enhancing ALKBH5-mediated removal of m6A methylation from BRCA1 mRNA, stabilizing BRCA1 mRNA, increasing DNA repair competency, and decreasing doxorubicin efficacy in breast cancer cells. |
PRMT5 inhibition and shRNA knockdown, m6A quantification, ALKBH5 subcellular fractionation/localization, BRCA1 mRNA stability measurement, DNA repair assays |
Molecular therapy : the journal of the American Society of Gene Therapy |
Medium |
35278676
|
| 2022 |
PRMT5 interacts with SMAD4 and methylates it at R361 upon TGF-β1 treatment. R361 methylation is required for SMAD complex formation and nuclear import, driving EMT and colorectal cancer metastasis. SMAD4 R361A mutation abolishes PRMT5/TGF-β1-induced metastasis. |
Mass spectrometry identification of R361 methylation, co-immunoprecipitation, immunofluorescence, SMAD complex formation assay, nuclear import assay, EMT and metastasis assays with mutant SMAD4 |
Oncogene |
Medium |
36991117
|
| 2021 |
PRMT5 functionally associates with EZH2 (confirmed by co-IP and GST pulldown). PRMT5 deposits H4R3me2s and H3R8me2s marks at the CDKN2B promoter; knockdown reduces these marks and the accompanying CpG methylation, reactivating CDKN2B expression. PRMT5 interaction with EZH2 leads to enhanced EZH2 binding and H3K27me3 at the CDKN2B locus. |
Co-immunoprecipitation, GST pulldown, ChIP assay (H4R3me2s, H3R8me2s, H3K27me3 at CDKN2B promoter), bisulfite sequencing, luciferase reporter |
Theranostics |
Medium |
33664859
|
| 2019 |
PRMT5 is required for B cell development and antibody responses in mice. PRMT5 prevents p53-dependent blocks at the Pro-B cell stage and p53-independent apoptosis in mature B cells during activation; it promotes germinal center expansion and ensures RNA splicing fidelity in germinal center B cells. |
Conditional B cell-specific Prmt5 knockout mice, flow cytometry, RNA-seq (splicing analysis), p53-dependency tested by genetic crosses |
Nature communications |
High |
30604754
|
| 2019 |
Zebrafish Prmt5 methylates germ cell-specific proteins Zili and Vasa (symmetric dimethylarginine) as well as histones H3R8me2s and H4R3me2s. Loss of Prmt5 reduces methylation of these substrates in gonads, downregulates Piwi pathway proteins, and causes germ cell apoptosis and failure of gonadal differentiation, leading to infertile male phenotype. |
Prmt5-null zebrafish model, immunostaining for H3R8me2s and H4R3me2s, western blot for Zili/Vasa methylation, gene expression analysis of meiosis/gonad genes |
Development (Cambridge, England) |
Medium |
31533925
|
| 2020 |
PRMT5 deletion in T cells reduces expression of the common gamma chain (γc), impairing IL-7-mediated survival and IL-2-mediated TCR-induced proliferation. PRMT5 is required for NKT cell development and peripheral T cell maintenance, homeostatic survival, and lymphopenic expansion in vivo. |
T cell-specific conditional PRMT5 knockout mice, flow cytometry, in vitro cytokine signaling assays, in vivo lymphopenic expansion model |
Frontiers in immunology |
Medium |
32328070
|
| 2015 |
PRMT5 methylates arginine residues in the third intracellular loop of the human D2 dopamine receptor. Mutation of these arginine residues reduces D2 receptor-mediated inhibition of cAMP signaling in HEK293T cells. In C. elegans, PRMT5 (prmt-5) promotes dopamine-mediated modulation of chemosensory and locomotory behaviors through the DOP-3 receptor. |
In vitro methylation assay of D2 receptor peptide by PRMT5, arginine-to-alanine mutagenesis of receptor, cAMP signaling assay in HEK293T cells, behavioral assays in prmt-5 C. elegans mutants |
Science signaling |
Medium |
26554819
|
| 2017 |
Menin and PRMT5 cooperate to suppress GLP1 receptor (GLP1R) transcript levels. In β-cells, PRMT5 (together with menin) suppresses PKA-mediated phosphorylation of FOXO1 and CREB downstream of GLP1 signaling, likely through arginine methyltransferase activity. |
Co-immunoprecipitation of menin-PRMT5 complex, gene expression analysis, phosphorylation assays for FOXO1 and CREB, small-molecule menin inhibitor rescue, ex vivo islet assays |
American journal of physiology. Endocrinology and metabolism |
Low |
28270438
|
| 2021 |
PRMT5 inhibition disrupts splicing of the ATF4 transcript, producing intron-retaining ATF4 mRNA that is detained in the nucleus, reducing cytoplasmic spliced ATF4 protein, downregulating ATF4 target genes, increasing oxidative stress, and inducing cellular senescence in AML cells. |
RNA sequencing, nuclear/cytoplasmic fractionation of ATF4 mRNA, ROS measurement, senescence assays, PRMT5 inhibitor treatment |
Redox biology |
Medium |
35305370
|
| 2023 |
PRMT5 symmetrically dimethylates MST2 (STK3) at R461 and R467 in its SARAH domain. This methylation suppresses MST2 autophosphorylation and kinase activity by blocking its homodimerization, inactivating the Hippo signaling pathway and promoting pancreatic cancer progression. |
In vitro methylation assay identifying R461/R467, co-immunoprecipitation, MST2 autophosphorylation assay, homodimerization assay, PRMT5 inhibitor (GSK3326595) in xenograft models |
The EMBO journal |
Medium |
37905571
|
| 2022 |
PRMT5 promotes symmetric dimethylation of NF-κB p65 at arginine 30 (R30) in vascular smooth muscle cells, leading to upregulation of VCAM-1 expression and macrophage adhesion. TMAO-induced Nox4-mediated ROS production drives PRMT5 expression, establishing a Nox4-PRMT5-VCAM-1 axis in TMAO-induced vascular inflammation. |
PRMT5 knockdown, VSMC-specific PRMT5 knockout mice, methylation assay of p65-R30, VCAM-1 expression and macrophage adhesion assays, ROS measurement |
Cell death & disease |
Medium |
35379776
|
| 2024 |
In cardiac fibroblasts, TGF-β stimulation promotes recruitment of a PRMT5/Smad3 complex to the α-SMA (ACTA2) promoter, increasing PRMT5-mediated H3R2 symmetric dimethylation. This mark is recognized by the WDR5/MLL1 methyltransferase complex, which then increases H3K4 trimethylation, enabling fibrotic gene transcription. Fibroblast-specific PRMT5 deletion reduces pressure overload-induced cardiac fibrosis in mice. |
ChIP assay of H3R2me2s at α-SMA promoter, Smad3 knockdown reducing H3R2me2s, co-IP of PRMT5/Smad3 complex, fibroblast-specific conditional KO mice, pressure overload model |
Nature communications |
High |
38503742
|
| 2023 |
PRMT5 methylates FoxO1 (symmetric dimethylarginine), destabilizing it. PRMT5 knockout in myoblasts increases total FoxO1 protein and promotes its cytoplasmic accumulation, activating autophagy and depleting lipid droplets, impairing muscle regeneration. Systemic autophagy inhibition in Prmt5MKO mice restores lipid droplets and moderately improves muscle regeneration. |
Myod1Cre-driven Prmt5 conditional KO mice, FoxO1 methylation and stability assays, subcellular fractionation, autophagy flux assays, lipid droplet quantification, genetic autophagy inhibition rescue |
Cell reports |
Medium |
37883229
|
| 2023 |
PRMT5 methylates SREBP1a at arginine residues, increasing its stability. Skeletal muscle-specific PRMT5 knockout reduces SREBP1a dimethylation and stability, impairing de novo lipogenesis. PRMT5 deletion also de-represses the Pnpla2 (ATGL) promoter via reduced H4R3me2s, elevating ATGL-mediated lipolysis. Double knockout of Pnpla2 and Prmt5 normalizes muscle mass and function. |
Skeletal muscle-specific Prmt5 KO mice, SREBP1a methylation and stability assays, ChIP of H4R3me2s at Pnpla2 promoter, double KO genetic rescue |
EMBO reports |
Medium |
37334900
|
| 2024 |
TBL2 acts as a scaffolding protein that promotes PRMT5-WDR77 (MEP50) interaction. This enhanced interaction increases PRMT5 methyltransferase activity and AKT phosphorylation, promoting breast cancer cell proliferation. |
Proteomic analysis, co-immunoprecipitation of TBL2-PRMT5-WDR77 complex, methyltransferase activity assay, AKT phosphorylation measurement, in vitro and in vivo proliferation assays |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
39499734
|
| 2025 |
PRMT5 catalyzes symmetric dimethylation of GPX4 at the conserved R152 residue. This methylation prolongs GPX4 half-life by preventing Cullin1-FBW7 E3 ligase binding to GPX4, thereby blocking ubiquitination-mediated GPX4 degradation and suppressing ferroptosis in cancer cells. |
In vitro methylation assay of GPX4-R152 by PRMT5, GPX4 half-life measurement, co-immunoprecipitation of GPX4 with FBW7 (with and without methylation), ubiquitination assay, PRMT5 inhibitor in vivo tumor models |
Nature cell biology |
High |
40033101
|
| 2025 |
PRMT5 directly catalyzes symmetric dimethylation of ALKBH5 at R316 (meR316-ALKBH5), enhancing TRIM28-mediated ALKBH5 ubiquitination and degradation. Reduced ALKBH5 decreases m6A demethylation of the CD276 transcript 3' UTR, increasing CD276 mRNA stability and expression, facilitating colorectal cancer immune evasion by inhibiting cytotoxic T-cell function. |
In vitro methylation assay identifying R316, co-IP of ALKBH5 with TRIM28, ubiquitination assay, m6A quantification on CD276 transcript, mRNA stability assay, in vivo and in vitro immune evasion assays |
Research (Washington, D.C.) |
Medium |
39781264
|
| 2021 |
PRMT5 regulates PRMT5-mediated dimethylation of Zili (PIWI protein) and Vasa in zebrafish gonads, controls Piwi pathway protein expression, and thereby governs germ cell development; these represent direct non-histone substrates of PRMT5 in vertebrate germline. |
Prmt5-null zebrafish, immunostaining for symmetric arginine dimethylation of Zili/Vasa, gene expression profiling |
Development (Cambridge, England) |
Medium |
31533925
|
| 2023 |
STC2 interacts with PRMT5 and activates it, leading to increased H4R3me2s. Activated PRMT5 promotes DNA double-strand break repair through both homologous recombination and non-homologous end joining pathways, and participates in SLC7A11-mediated ferroptosis resistance in a PRMT5-dependent manner in esophageal squamous cell carcinoma. |
Co-immunoprecipitation of STC2-PRMT5, H4R3me2s western blot, DNA repair pathway assays (HR and NHEJ), SLC7A11 expression assays, in vivo validation |
Redox biology |
Medium |
36764215
|
| 2021 |
PRMT5 inhibition in multiple myeloma de-represses CASP1 expression (negatively correlated with PRMT5 levels), leading to CASP1-dependent pyroptosis. PRMT5 silences CASP1 via its histone methyltransferase activity (H4R3me2s). |
PRMT5 knockdown, PRMT5 inhibitor treatment, CASP1 expression measurement, pyroptosis markers (N-GSDMD, IL-1b, IL-18), correlation of PRMT5 and CASP1 expression |
Cell death & disease |
Low |
34531375
|
| 2023 |
PRMT5 methylates KLF5 at arginine 41 (R41) in a methyltransferase-activity-dependent manner. This dimethylation stabilizes KLF5 protein by promoting the Akt/GSK3β signaling axis, reducing its degradation and maintaining lung cancer cell proliferation. |
Co-immunoprecipitation (PRMT5-KLF5), in vitro methylation assay (R41 site), protein stability assays, KLF5 downstream target analysis, in vivo xenograft with PRMT5 inhibition |
Journal of cellular and molecular medicine |
Medium |
37461162
|
| 2025 |
MST4 kinase, transactivated by NRF2, phosphorylates PRMT5 at S439 and S463 and promotes PRMT5 interaction with METTL3, stimulating PRMT5's methyltransferase activity. PRMT5 then methylates METTL3 at R36 (METTL3-R36me2); this methylation recruits METTL3 to DNA damage sites, promoting RAD51 recruitment for HR-mediated double-strand break repair and cisplatin resistance in ovarian cancer. |
In vitro phosphorylation assay (MST4 on PRMT5), co-IP showing increased PRMT5-METTL3 interaction upon phosphorylation, methylation assay identifying R36, ChIP showing METTL3 recruitment to DSB sites, RAD51 foci assay, xenograft model |
Cell reports |
Medium |
40158218
|
| 2023 |
PRMT5-mediated methylation of G3BP2 at R468 (G3BP2-R468me2) enhances G3BP2 binding to the deubiquitinase USP7, promoting deubiquitination and stabilization of G3BP2, which activates ACLY and stimulates de novo lipogenesis and tumorigenesis in head and neck squamous carcinoma. |
Co-IP of G3BP2-USP7 interaction with and without PRMT5, methylation assay identifying R468, ubiquitination/deubiquitination assay, ACLY activity assay, lipogenesis measurement |
Cell death & disease |
Medium |
36878903
|
| 2023 |
PRMT5 inhibition in breast cancer stem cells disrupts splicing of DNA repair genes involved in Fanconi Anemia and homologous recombination pathways (including ATM, DDX11, EXO1, FAN1, SLX4, ATR, RAD17, RAD51D, RUVBL1), causing nuclear retention of intron-containing transcripts and production of non-canonical isoforms with compromised protein function rather than gene expression repression. |
RNA sequencing of PRMT5-inhibited BCSCs vs bulk cells, identification of skipped exon and retained intron events, nuclear vs cytoplasmic fractionation of transcripts, apoptosis assays |
Oncogene |
Medium |
39695328
|
| 2021 |
PRMT5 promotes vascular morphogenesis in zebrafish through transcriptional control of ETS transcription factors and adhesion proteins in endothelial cells. Using a catalytic dead PRMT5 mutant, it was demonstrated that methyltransferase activity is dispensable for vessel formation but required for blood cell formation; PRMT5 acts as a scaffold protein facilitating chromatin looping to regulate transcription during vascular morphogenesis. |
Zebrafish prmt5 loss-of-function, catalytic dead PRMT5 mutant rescue experiments, pharmacological methyltransferase inhibition, chromatin conformation assays (reporter gene analysis), ChIP |
PLoS genetics |
Medium |
34153034
|
| 2023 |
PRMT5 catalyzes symmetric dimethylation of PRMT5 at CAMK2N1's promoter via H4R3me2s and H3R8me2s marks, repressing CAMK2N1 transcription in prostate cancer cells. This silencing promotes prostate cancer progression in vitro and in vivo. |
ChIP assay of H4R3me2s and H3R8me2s at CAMK2N1 promoter, shRNA knockdown and rescue, PRMT5 inhibitor, in vivo tumor growth assays |
Molecular cancer |
Low |
35624451
|
| 2023 |
PRMT5 methylates ULK1 at R532 (monomethylation), suppressing ULK1 activation and attenuating autophagy. Loss or inhibition of PRMT5 removes this methylation, activating ULK1 and triggering cytoprotective autophagy. ULK1 inhibition blocks PRMT5-deficiency-induced autophagy and sensitizes cells to PRMT5 inhibitor. |
In vitro methylation assay (ULK1 R532), ULK1 activity assay, autophagy flux assays, ULK1 inhibitor and genetic ablation epistasis experiments, PRMT5 inhibitor sensitivity assays |
Scientific reports |
Medium |
37400460
|
| 2023 |
Alpha-synuclein overexpression enhances BAF complex interaction with PRMT5, globally increasing H4R3me2s symmetric dimethylation. This results in H4R3me2s accumulation near the NRCAM transcription start site and negative regulation of NRCAM, a neuronal differentiation gene. ChIP-seq confirmed H4R3me2s accumulation at the NRCAM locus. |
Mass spectrometry interactome of nuclear alpha-synuclein (identifying BAF-PRMT5 interaction), ChIP-seq for H4R3me2s, transcriptomic analysis of NRCAM |
The FEBS journal |
Low |
38105619
|