• Assay Selection Tool

BellBrook Labs

  • Products
    • Transcreener® HTS Assay Kits
      • Transcreener® ADP² Kinase Assay Kits
        • Transcreener® ADP2 Assay Kit – FP Readout
        • Transcreener® ADP2 Assay Kit – FI Readout
        • Transcreener® ADP2 Assay Kit – TR-FRET Readout
      • Transcreener® ADO CD73 Assay Kit
      • Transcreener® AMP²/GMP² Phosphodiesterase Assay Kits
        • Transcreener® AMP2/GMP2 FP Assay
        • Transcreener® AMP2/GMP2 Assay Kit – TR-FRET Readout
      • Transcreener® cGAMP cGAS Assay Kits
        • Transcreener® cGAMP Assay Kit – FP Readout
        • Transcreener® cGAMP Assay Kit – TR-FRET Readout
      • Transcreener dAMP Exonuclease Assay Kit
      • Transcreener® EPIGEN SAH Methyltransferase Assay Kit
      • Transcreener® GDP GTPase Assay Kits
        • Transcreener® GDP Assay Kit – FP Readout
        • Transcreener® GDP Assay Kit – FI Readout
        • Transcreener® GDP Assay Kit – TR-FRET Readout
      • Transcreener® UDP² Glycosyltransferase Assay Kits
        • Transcreener® UDP2 Assay Kit – FP Readout
        • Transcreener® UDP2 Assay Kit – FI Readout
        • Transcreener® UDP2 Assay Kit – TR-FRET Readout
      • Transcreener® 2-5A OAS Assay Kit
    • AptaFluor® HTS Assay Kits
      • AptaFluor® SAH Methyltransferase Assay Kit
    • Enzyme Assay Systems
      • TREX1 Assay System
    • Recombinant Enzymes
      • Human cGAS Enzyme
      • Mouse cGAS Enzyme
      • Human DDX3 Enzyme
      • Human OAS1 Enzyme
      • Human TREX1 Enzyme
    • Assay Plates
    • Ordering Information
  • Services
    • Assay Development Services
    • Lead Discovery Services
    • CD38 Assay Services
    • GTPase Profiling Services
    • ATPase Profiling Services
  • Assays by Target
    • Kinase Assays
      • ADK Assays – Application
      • AMPK Assays – Application
      • IKK-beta Assays – Application
      • IRAK4 Assays – Application
      • JAK1 Assays – Application
      • JAK3 Assays – Application
      • MAPK8 Assays – Application
      • PKR Assays – Application
      • RIPK1 Assays – Application
      • RIPK2 Assays – Application
      • TBK1 Assays – Application
    • GTPase Assays
      • GAP Assays – Application
      • GEF Assays – Application
      • KRAS Assays – Application
      • HRAS Assays – Application
      • NRAS Assays – Application
      • RRAS Assays – Application
      • Rac1 Assays – Application
      • RhoA Assays – Application
      • RhoC Assays – Application
      • Cdc42 Assays – Application
      • Ran Assays – Application
    • Methyltransferase Assays
      • EZH2 Assays – Application
      • G9a Assays – Application
      • SET7/9 Assays – Application
      • SET8 Assays – Application
      • PRMT1 Assays – Application
      • PRMT3 Assays – Application
      • PRMT4 Assay – Application
    • STING Pathway Assays
      • cGAS Assay Kits
      • ENPP1 Assays – Application
      • TREX1 Assay System
      • IKK-beta Assays – Application
      • TBK1 Assays – Application
    • Nucleotidase Assays
      • CD38 Assay Services
      • CD39 Assays – Application
      • CD73 Activity Assay Kits
    • Helicase / ATPase Assays
      • DDX3 Assays – Application
      • NSP13 Assays – Application
      • P97 Assays – Application
    • Glycosyltransferase Assays
      • Toxin B Assays – Application
      • GALNT2 Assays – Application
      • GALNT3 Assays – Application
      • BGalT1 Assays – Application
    • Phosphodiesterase Assays
      • PDE3 Assays – Application
      • PDE4 Assays – Application
      • PDE5 Assays – Application
      • PDE7 Assays – Application
    • Ligase and Synthetase Assays
      • SUMO E1 Assays – Application
      • Acyl CoA Synthetase Assays – Application
      • S-Acetyl CoA Synthetase Assays – Application
    • Exonuclease Assays
      • TREX1 Assay System
    • OAS Assays
      • OAS1 Assay Kits
    • Other Enzyme Assays
      • NUDT5 Assays – Application
  • Resources
    • Technical Manuals
    • Transcreener® Assays – Instrument Compatibility
    • Application Notes
    • Posters and Presentations
    • Publications
    • Transcreener® FAQ’s
    • Guides
      • Residence Time Guide
      • Hit Prioritization Guide
      • Kinases in Innate Immunity
  • Company
    • President’s Message
    • International Distributors
    • Careers
    • Downloads
    • Contact Us
  • Blog
  • MY CART
    No products in cart.

PRMT5 is Innately Interesting

by Bellbrook Labs / Wednesday, 30 March 2022 / Published in Emerging Targets, Epigenetics, Innate Immunity
PRMT5 Role with Macrophages

PRMT5 is a type II arginine methyltransferase that dimethylates arginine residues symmetrically. Its various functions extend into T cell development, B cell regulation, hematopoiesis, and mitotic control. In the past, research on PRMT5 primarily focused on cancer and the adaptive immune response. These are both situations where metabolism and growth are critical. Recent reports implicate PRMT5 in aspects of innate immunity via both its traditional role and the inhibition of viral replication by a non-arginine methyltransferase modality.1

PRMT5 in the Nucleus and the Cytoplasm

Cyclic GMP-AMP synthase (cGAS) is part of the innate immune system, with separate functions in the cytoplasm and the nucleus. Upon sensing the presence of cytoplasmic double-stranded DNA and binding to it, cytosolic cGAS induces the production of cGAMP, activating STING-TBK1-IRF3 signaling that culminates in an antiviral response via type 1 interferons and pro-inflammatory cytokines. PRMT5 acts to suppress this cascade by symmetrical dimethylation of the cytosolic cGAS Arg124 residue, blocking its cytosolic DNA binding abilities. Without the activity of PRMT5, infection by DNA viruses is greatly diminished, but autoimmunity is greatly enhanced.2 In the nucleus, nuclear cGAS recruits PRMT5 in the presence of double-stranded RNA, facilitating its binding to the promoters/enhancers of IfnB and IfnA4.  This leads to the symmetrical dimethylation of Histone H3 arginine 2 (H3R2Me2s), allowing greater transcriptional access by factors that increase type 1 IFN production. So, in the cytoplasm, PRMT5 modulates the innate response to DNA viruses, while, in the nucleus, it activates the innate response to RNA viruses.3

PRMT5 in Macrophages

In macrophages, PRMT5 has been shown to associate with nuclear Carbonic Anhydrase 6B (CA VI-B) to upregulate the expression of the pro-inflammatory cytokine IL-12 in an innate response to intracellular bacterial infection. By its nuclear association with PRMT5, CA VI-B interferes with PRMT5’s symmetrical dimethylation of Histone H3 arginine 8, inhibiting H3R8me2s histone modification at the IL-12 promoter region. This allows c-Rel greater access to the IL-12b promoter, resulting in increased IL-12 expression. In essence, PRMT5 acts to modulate this response in macrophages in the absence of bacterial provocation.4

The Dual Role of PRMT5 in Chronic HBV Infection

In a blended response, PRMT5 exerts a profound antiviral effect on Hepatitis B (HBV) infection. Persistent HBV infections cause the formation of covalently closed circles of the viral DNA genome (cccDNA), creating minichromosomes. These structures further enable the transcription of viral RNAs. In vitro and in vivo, the symmetrical dimethylation of arginine 3 on H4 of the cccDNA by PRMT5 repressed viral gene transcription. Through a non-arginine methyltransferase process, PRMT5 also binds to the reverse transcriptase-ribonuclease H region of the HBV polymerase, hampering pregenomic RNA encapsidation.5

While PRMT5’s modulation of the innate immune response seems to only increase in complexity, it also yields promising insights for the treatment of infection and autoimmunity.

Study PRMT5 with the AptaFluor SAH Methyltransferase Assay

References

  1. Strobl, C.D. et al. (2019) Selective PRMT5 Inhibitors Suppress CD8+ T Cells by Upregulation of p53 and Impairment of the AKT Pathway Similar to the Tumor Metabolite TMA. Molecular Cancer Therapeutics, 19(2), 409-419. https://doi.org/10.1158/1535-7163.MCR-19-0189.
  2. Ma, D. et al. (2021) Arginine Methyltransferase PRMT5 Negatively Regulates cGAS-Mediated Antiviral Immune Response. Science Advances, 7(13), 1-14. https://doi.org/10.1126/sciadv.abc1834.
  3. Cui, S. et al. (2020) Nuclear cGAS Functions Non-canonically to Enhance Antiviral Immunity via Recruiting Methyltransferase Prmt5. Cell Reports, 33(10), 1-15. https://doi.org/10.1016/j.cellrep.2020.108490
  4. Xu, J. (2017) Nuclear Carbonic Anhydrase 6B Associates with PRMT5 to Epigenetically Promote IL-12 Expression in Innate Response. PNAS, 114(32), 8620-8625. https://doi.org/10.1073/pnas.1700917114.
  5. Zhang, W. et al. (2017) PRMT5 Restricts Hepatitis B Virus Replication Through Epigenetic Repression of Covalently Closed Circular DNA Transcription and Interference with Pregenomic RNA Encapsidation. Hepatology, 66(2), 398-415. https://doi.org/10.1002/hep.29133
Tagged under: AptaFluor SAH Methyltransferase Assay, Lead Discovery Services, PRMT5

What you can read next

ADP Detection: It’s not all about kinases
Fear: An Inherited Trait?
Glycosyltransferase Activity Assay and Lysosomal Storage Disorders
Using a Glycosyltransferase Activity Assay to Study Glycosylation and the Function of GTs

Categories

  • Company
  • Emerging Targets
  • Epigenetics
  • HTS Assays
  • Innate Immunity
  • Neurodegenerative Diseases
  • News
  • Products
  • Resources
  • Success Stories
  • Uncategorized

Recent Posts

  • PARP1 as a Hero vs Villain

    Is PARP1 a Hero or Villain?

    Not counting histones, PARP1 [Poly(ADP-ribose) ...
  • Ongoing Puzzle of c-SRC in Cancer Treatment

    Advancements in The Ongoing Puzzle to Understand c-SRC

    Nearly a half-century ago, sequences from the R...
  • SLAS 2023 Conference Exhibitor Announcement

    SLAS 2023 – HTS Assays and Discovery Services

    BellBrook Labs will exhibit and present posters...
  • BTK's Involved in Systemic lupus erythematosus

    The Challenging Search for BTK Inhibitors

    Bruton’s Tyrosine Kinase (BTK) is a 76kDa...
  • SARM1 Causes Axonal Death

    SARM1 Forefronts Research into Major Neurological Diseases

    SARM1 [Sterile alpha & toll/interleukin rec...

Archives

BellBrook Labs
5500 Nobel Drive, Suite 230
Madison, Wisconsin 53711 USA
(608) 443-2400

info@bellbrooklabs.com

 Copyright © 2023 BellBrook Labs | All Rights Reserved | Privacy Policy | Terms of Use | FCOI | Sitemap

TOP