Affinage

Showing POLR3F — C34 is a alias.

POLR3F

DNA-directed RNA polymerase III subunit RPC6 · UniProt Q9H1D9

Length
316 aa
Mass
35.7 kDa
Annotated
2026-06-10
39 papers in source corpus 3 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POLR3F (RPC34/C34) is a subunit of RNA polymerase III that serves as a central determinant of pol III recruitment and initiation competence by docking the enzyme onto the pre-initiation complex through direct contact with TFIIIB (PMID:9312031, PMID:10329159). Mutational analysis of the yeast subunit resolves two mechanistically distinct contributions: one C34 surface mediates pol III affinity for the pre-initiation complex, while a second is required for open complex formation during initiation, with catalytic activity on non-specific templates remaining intact (PMID:9312031). The C34–TFIIIB interface is genetically essential, mapping to conserved regions II and III of the TFIIIB70 (BRF) C-terminal extension whose mutation is co-lethal with rpc34 alleles and impairs specific tRNA gene transcription (PMID:10329159). C34 additionally acts as a regulatory hub: its WH1 domain is the principal docking site for the repressor MAF1, and TFIIIB BRF1 competes with MAF1 for this same interface, coupling MAF1 phosphorylation status to pol III derepression and TFIIIB-mediated activation (PMID:32641350).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 1997 High

    Established that C34 is not merely a structural subunit but a functional determinant linking pol III to its initiation machinery, distinguishing recruitment from a downstream initiation step.

    Evidence In vitro mutagenesis of RPC34, purification of mutant pol III, and transcription assays comparing non-specific vs. specific templates in yeast

    PMID:9312031

    Open questions at the time
    • Did not define the structural surface of C34 contacting the pre-initiation complex
    • Mechanism of open complex formation defect at residue level not resolved
    • Not extended to mammalian POLR3F
  2. 1999 High

    Mapped the partner side of the interaction, showing the C34 docking site on TFIIIB70 (BRF) is genetically essential and required for specific transcription.

    Evidence Mutagenesis of TFIIIB70 with reciprocal co-lethality against rpc34 alleles, binding assays, and in vitro transcription of the SUP4 tRNA gene in yeast

    PMID:10329159

    Open questions at the time
    • Did not provide an atomic-resolution structure of the C34–TFIIIB70 interface
    • Did not establish how the same interface is regulated
  3. 2020 Medium

    Identified the C34 WH1 domain as a shared docking platform for both the repressor MAF1 and activating TFIIIB BRF1, revealing a phosphorylation-gated competitive switch controlling pol III activity.

    Evidence NMR analysis of CsMAF1, pulldown and competition assays with CsC34 and BRF1 C-terminus, and AGC1 kinase phosphorylation assays in citrus (plant ortholog)

    PMID:32641350

    Open questions at the time
    • Single lab and plant ortholog rather than mammalian POLR3F
    • Structural detail of the C34 WH1 surface engaging MAF1 versus BRF1 not fully resolved
    • In vivo consequences of the competitive switch on pol III gene programs not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether the recruitment, open-complex, and MAF1/BRF1 regulatory functions defined in yeast and plants are conserved at the mammalian POLR3F protein remains open.
  • No direct functional or structural characterization of human POLR3F in the available corpus
  • MAF1-mediated regulation of the human C34 interface not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3
Partners
BRF1MAF1TFIIIB70
Complex memberships
RNA polymerase III

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 The C34 subunit (RPC34/POLR3F) of yeast RNA polymerase III interacts with TFIIIB70, and mutations in RPC34 that impair this interaction also impair specific transcription of pol III genes. Purified mutant pol III enzymes showed normal catalytic activity on non-specific templates but were defective in specific transcription: one mutant (C34-1124) reduced pol III affinity for pre-initiation complexes, while a second (C34-1109) was defective in open complex formation during initiation. This demonstrates that C34 is a major determinant in pol III recruitment by the pre-initiation complex and also acts at a subsequent step required for formation of an initiation-competent polymerase. In vitro mutagenesis of RPC34; purification of mutant pol III; in vitro transcription assays on poly[d(A-T)] and specific pol III gene templates; complementation by increasing pol III concentration The EMBO journal High 9312031
1999 The C-terminal extension of yeast TFIIIB70 (BRF) contains conserved regions II and III that are required for interaction with the C34 subunit (POLR3F ortholog) of RNA pol III. Mutations in region II of TFIIIB70 that impair C34 binding are co-lethal with rpc34 mutations, establishing a genetically essential TFIIIB70–C34 interface. Separately, region II mutations impair TBP binding and TFIIIB assembly, and mutations in the TFIIIB70–C34 interface impair in vitro transcription of the SUP4 tRNA gene. Extensive mutagenesis of TFIIIB70; co-lethality (genetic epistasis) with rpc34 alleles; in vitro binding assays; suppression by TBP overexpression; in vitro transcription of SUP4 tRNA gene Journal of molecular biology High 10329159
2020 Citrus MAF1 (CsMAF1) binds predominantly to the WH1 domain of the Pol III C34 subunit (CsC34, ortholog of POLR3F). The phosphoregulatory region of CsMAF1 (loop-3 and α-helix-2) contributes to this interaction, and phosphorylation of this region (including Ser45, phosphorylated by a citrus AGC1 kinase) decreases CsMAF1 affinity for CsC34, leading to Pol III derepression. Additionally, the C-terminal region of TFIIIB component BRF1 competes with CsMAF1 for binding to CsC34, indicating that CsC34 is a shared docking site for both MAF1-mediated repression and TFIIIB-mediated activation. NMR structural analysis of CsMAF1; pulldown/binding assays between CsMAF1 and CsC34; phosphorylation assays with AGC1 kinase; competition assays with BRF1 C-terminal region; mutagenesis of Ser45 The Plant cell Medium 32641350

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Different from the HIV fusion inhibitor C34, the anti-HIV drug Fuzeon (T-20) inhibits HIV-1 entry by targeting multiple sites in gp41 and gp120. The Journal of biological chemistry 203 15640162
1997 Dual role of the C34 subunit of RNA polymerase III in transcription initiation. The EMBO journal 94 9312031
2006 Maternal transfer of complement components C3-1, C3-3, C3-4, C4, C5, C7, Bf, and Df to offspring in rainbow trout (Oncorhynchus mykiss). Immunogenetics 93 16550351
2003 HIV-1 resistance to the gp41-dependent fusion inhibitor C-34. Antiviral research 62 12895697
2008 Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice. The Journal of biological chemistry 60 18809675
2013 Conjugation of cholesterol to HIV-1 fusion inhibitor C34 increases peptide-membrane interactions potentiating its action. PloS one 53 23565220
1999 Mutagenesis of yeast TFIIIB70 reveals C-terminal residues critical for interaction with TBP and C34. Journal of molecular biology 44 10329159
2021 TLR4-IN-C34 Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses via Downregulating TLR4/MyD88/NF-κB/NLRP3 Signaling Pathway and Reducing ROS Generation in BV2 Cells. Inflammation 34 34727285
2017 Alismanin A, a Triterpenoid with a C34 Skeleton from Alisma orientale as a Natural Agonist of Human Pregnane X Receptor. Organic letters 33 29016144
2005 Differential inhibition of HIV-1 and SIV envelope-mediated cell fusion by C34 peptides derived from the C-terminal heptad repeat of gp41 from diverse strains of HIV-1, HIV-2, and SIV. Journal of medicinal chemistry 28 15828842
2001 Variant toxin B and a functional toxin A produced by Clostridium difficile C34. FEMS microbiology letters 27 11430410
2019 Heterologous Expression of a Cryptic Gene Cluster from Streptomyces leeuwenhoekii C34T Yields a Novel Lasso Peptide, Leepeptin. Applied and environmental microbiology 22 31562169
1993 Anticodon bases C34 and C35 are major, positive, identity elements in Saccharomyces cerevisiae tRNA(Trp). Nucleic acids research 15 8255761
2019 Pharmacological inhibition of TLR4/NF-κB with TLR4-IN-C34 attenuated microcystin-leucine arginine toxicity in bovine Sertoli cells. Journal of applied toxicology : JAT 14 30671980
2016 Glycosyl Phosphatidylinositol-Anchored C34 Peptide Derived From Human Immunodeficiency Virus Type 1 Gp41 Is a Potent Entry Inhibitor. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 14 27155865
2005 Development of anti-HIV agents targeting dynamic supramolecular mechanism: entry and fusion inhibitors based on CXCR4/CCR5 antagonists and gp41-C34-remodeling peptides. Current HIV research 14 16250877
2020 Bungsteroid A: One Unusual C34 Pentacyclic Steroid Analogue from Zanthoxylum bungeanum Maxim. The Journal of organic chemistry 12 32702985
2019 Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV-1 Fusion Inhibitors. Chembiochem : a European journal of chemical biology 12 31012222
2012 Preexposure prophylaxis with albumin-conjugated C34 peptide HIV-1 fusion inhibitor in SCID-hu Thy/Liv mice. Antimicrobial agents and chemotherapy 12 22252805
2007 C34, a membrane fusion inhibitor, blocks HIV infection of langerhans cells and viral transmission to T cells. The Journal of investigative dermatology 12 17255952
2019 Synthesis and Biological Activities of Aplyronine A Analogues toward the Development of Antitumor Protein-Protein Interaction Inducers between Actin and Tubulin: Conjugation of the C1-C9 Macrolactone Part and the C24-C34 Side Chain. ACS omega 11 31459949
2005 Clinical significance and neuropathology of primary MADD in C34-T and G468-T mutations of the AMPD1 gene. Clinical neuropathology 11 15803807
2018 Analysis of metabolic networks of Streptomyces leeuwenhoekii C34 by means of a genome scale model: Prediction of modifications that enhance the production of specialized metabolites. Biotechnology and bioengineering 10 29578590
2017 A first-in-human study of the novel HIV-fusion inhibitor C34-PEG4-Chol. Scientific reports 9 28842581
2015 Molecular weight-dependent degradation of D-lactate-containing polyesters by polyhydroxyalkanoate depolymerases from Variovorax sp. C34 and Alcaligenes faecalis T1. Applied microbiology and biotechnology 9 26109003
2015 The C34 Peptide Fusion Inhibitor Binds to the Six-Helix Bundle Core Domain of HIV-1 gp41 by Displacement of the C-Terminal Helical Repeat Region. Biochemistry 9 26506247
2011 The effect of SAMe and betaine on Hepa 1-6, C34 and E47 liver cell survival in vitro. Experimental and molecular pathology 9 22032937
2022 Pharmacological inhibition of toll-like receptor 4 with TLR4-IN-C34 modulates the intestinal flora homeostasis and the MyD88/NF-κB axis in ulcerative colitis. European journal of pharmacology 8 36152840
2022 TLR4-IN-C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis. Iranian journal of basic medical sciences 7 36474570
2021 The C29-C34 parts of antitumor macrolide aplyronine A serve as versatile actin-affinity tags. Chemical communications (Cambridge, England) 7 34553712
2020 The MAF1 Phosphoregulatory Region Controls MAF1 Interaction with the RNA Polymerase III C34 Subunit and Transcriptional Repression in Plants. The Plant cell 7 32641350
2014 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. PloS one 6 25393106
2024 A New Chimeric Antibody against the HIV-1 Fusion Inhibitory Peptide MT-C34 with a High Affinity and Fc-Mediated Cellular Cytotoxicity. Biology 5 39336102
2025 Benzo[a]phenoxazine derivative C34 efficacy against fluconazole-resistant Candida spp. Microbial pathogenesis 3 40122407
2005 Hyperleptinemia and its relation with peripheral C34(+)CD7(+) stem cells in renal transplant recipients. Transplant immunology 3 16431293
2025 Neuroprotective Effects of Early TLR4 Blockade with Compound C34 in Temporal Lobe Epilepsy: Alleviation of Neuroinflammation and Apoptosis. Iranian journal of pharmaceutical research : IJPR 0 40718441
2025 TLR4-IN-C34 attenuates the progression of osteoarthritis through inhibiting inflammation, angiogenesis and pain. Cellular signalling 0 40854507
2025 Metabolic Engineering of Streptomyces leeuwenhoekii C34T to Increase Chaxamycin Production Based on the iVR1007 Genome-Scale Model. Biotechnology and bioengineering 0 40956005
2024 [Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line]. Molekuliarnaia biologiia 0 39709562

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