Page last updated: 2024-10-24

cytosolic DNA-directed RNA polymerase complex

Definition

Target type: cellularcomponent

The eubacterial DNA-directed RNA polymerase is a multisubunit complex with a core composed of the essential subunits beta-prime, beta, and two copies of alpha and a fifth nonessential subunit called omega. An additional subunit, a sigma factor, is required for promoter recognition and specificity. [PMID:11158566]

The cytosolic DNA-directed RNA polymerase complex, also known as the cGAS-STING pathway, is a crucial component of the innate immune system responsible for detecting and responding to cytosolic DNA. This complex is assembled in the cytoplasm upon detection of foreign or self DNA, triggering an antiviral and anti-inflammatory response. Here is a detailed description of its cellular components:

**1. Cyclic GMP-AMP Synthase (cGAS):** This enzyme acts as the primary sensor of cytosolic DNA. Upon binding to DNA, cGAS catalyzes the production of cyclic GMP-AMP (cGAMP), a second messenger molecule.

**2. Stimulator of Interferon Genes (STING):** STING is a transmembrane protein located in the endoplasmic reticulum (ER). It binds to cGAMP, triggering a signaling cascade.

**3. TANK-Binding Kinase 1 (TBK1):** This kinase is recruited to the STING complex upon cGAMP binding. TBK1 phosphorylates downstream signaling proteins, including IRF3.

**4. Interferon Regulatory Factor 3 (IRF3):** IRF3 is a transcription factor that becomes activated upon phosphorylation by TBK1. Activated IRF3 translocates to the nucleus and induces the expression of type I interferons (IFNs).

**5. Type I Interferons (IFNs):** These cytokines, primarily IFN-α and IFN-β, are key mediators of the antiviral response. They act on neighboring cells to induce an antiviral state, inhibit viral replication, and activate other immune cells.

**6. Additional Components:** Other cellular components that contribute to the functionality of the cytosolic DNA-directed RNA polymerase complex include:
* **TBK1-binding protein 1 (TBKBP1):** This protein is thought to enhance TBK1 activity.
* **Adaptor protein myeloid differentiation primary response gene 88 (MyD88):** MyD88 can interact with STING and contribute to the activation of NF-κB, another transcription factor involved in the immune response.

**In summary,** the cytosolic DNA-directed RNA polymerase complex is a multi-component signaling cascade that effectively recognizes and responds to the presence of cytosolic DNA. This pathway plays a crucial role in defending against viral infections and other threats to cellular integrity.'
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Proteins (4)

ProteinDefinitionTaxonomy
DNA-directed RNA polymerase subunit betaA DNA-directed RNA polymerase subunit beta that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A8V2]Escherichia coli K-12
DNA-directed RNA polymerase subunit beta'A DNA-directed RNA polymerase subunit beta that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A8T7]Escherichia coli K-12
DNA-directed RNA polymerase subunit omegaA DNA-directed RNA polymerase subunit omega that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A800]Escherichia coli K-12
DNA-directed RNA polymerase subunit alphaA DNA-directed RNA polymerase subunit alpha that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A7Z4]Escherichia coli K-12

Compounds (2)

CompoundDefinitionClassesRoles
quinacrinequinacrine : A member of the class of acridines that is acridine substituted by a chloro group at position 6, a methoxy group at position 2 and a [5-(diethylamino)pentan-2-yl]nitrilo group at position 9.

Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.
acridines;
aromatic ether;
organochlorine compound;
tertiary amino compound
antimalarial;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor
rifamycin svrifamycin SV : A member of the class of rifamycins that exhibits antibiotic and antitubercular properties.

rifamycin SV: RN given refers to parent cpd; structure in Merck Index, 9th ed, #8009
acetate ester;
cyclic ketal;
lactam;
macrocycle;
organic heterotetracyclic compound;
polyphenol;
rifamycins
antimicrobial agent;
antitubercular agent;
bacterial metabolite