Affinage

POLR3C

DNA-directed RNA polymerase III subunit RPC3 · UniProt Q9BUI4

Length
534 aa
Mass
60.6 kDa
Annotated
2026-06-10
30 papers in source corpus 2 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 2/4 claims corpus-supported (50%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POLR3C (RPC62) is a structural subunit of RNA Polymerase III that contributes to promoter-specific transcription initiation by directly assembling with RPC32 (PMID:26394183). The crystal structure of the human RPC62–RPC32β complex shows that RPC32β engages the extended winged-helix domains (eWH1/eWH2) and the coiled-coil domain of RPC62 and bridges these RPC62 domains, while fitting into Pol III EM density places the subcomplex at the polymerase surface where RPC32 simultaneously contacts the largest Pol III subunit and exposes residues for external interactions (PMID:26394183). A minimal RPC32 core domain is sufficient for this interface, a binding mode shared by both RPC32 isoforms (PMID:26394183). Functional conservation of the subunit's role in Pol III transcription is supported by trypanosomatid orthologs, where the C82 ortholog localizes to the nucleus, associates with tRNA and 5S rRNA gene loci, and is required for their expression and for cell viability (PMID:39523652). Beyond the structural definition of the RPC62–RPC32 interface and ortholog-based functional evidence, no further mechanistic detail of POLR3C has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2015 High

    Established the structural basis of how POLR3C/RPC62 is incorporated into Pol III, showing RPC32 bridges the eWH1/eWH2 and coiled-coil domains of RPC62 and positions the subcomplex at the polymerase surface.

    Evidence X-ray crystallography of the human RPC62–RPC32β core domain complex fitted into Pol III EM density

    PMID:26394183

    Open questions at the time
    • Does not resolve how this subcomplex contributes mechanistically to promoter recognition or open-complex formation
    • Functional consequences of the proposed solvent-exposed external interactions not tested
    • Isoform-specific (RPC32α vs RPC32β) functional differences not addressed structurally
  2. 2015 High

    Defined the minimal RPC32 core domain sufficient for RPC62 interaction and showed both RPC32 isoforms use the same binding mode, delimiting the assembly interface.

    Evidence Co-crystallization and deletion mapping of the RPC32β core domain with RPC62

    PMID:26394183

    Open questions at the time
    • Stem-cell-restricted RPC32α context not directly co-crystallized
    • Affinity/kinetics of the interface and its contribution to holoenzyme stability not quantified
  3. 2024 Medium

    Demonstrated functional conservation of the subunit's role in Pol III–dependent gene expression using trypanosomatid orthologs, while revealing a divergence in subcomplex partners.

    Evidence RNAi knockdown with RNA quantification, ChIP, TAP-MS, and nuclear localization microscopy in T. brucei and L. major

    PMID:39523652

    Open questions at the time
    • Divergent organism — RPC32 ortholog (C31) was not detected as a partner, so the human RPC62–RPC32 interface may not be conserved
    • Does not establish the human POLR3C loss-of-function phenotype
    • Partner C34 interaction not structurally mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How POLR3C contributes mechanistically to Pol III initiation, recruitment, and isoform-specific transcription programs in human cells remains unresolved.
  • No direct human loss-of-function or transcriptional profiling in the corpus
  • Role of solvent-exposed external interaction surface untested functionally
  • No disease association established in the available corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 1
Partners
C34RPC32
Complex memberships
RNA Polymerase IIIRPC62/RPC39/RPC32 subcomplex

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 Crystal structure of the human RPC62 (POLR3C)–RPC32β complex revealed that RPC32β binds to the extended winged-helix 1 and 2 (eWH1/eWH2) domains and the coiled-coil domain of RPC62, acting as a molecular bridge between these RPC62 domains. Fitting of the complex into existing EM density of Pol III suggests that RPC32 has a bi-functional role: contacts with the largest Pol III subunit on one face, and solvent-exposed residues available for external interactions on the other. X-ray crystallography of the RPC62–RPC32β core domain complex, combined with fitting into Pol III EM density Journal of structural biology High 26394183
2015 A minimal core-interacting domain of RPC32 sufficient for interaction with RPC62 was identified; RPC32β (but not the stem-cell-restricted RPC32α isoform context) was used to define this interface, and the two RPC32 isoforms share this core binding mode with RPC62. Co-crystallization and deletion mapping of the RPC32β core domain with RPC62 Journal of structural biology High 26394183
2024 In trypanosomatid orthologs (T. brucei and L. major), C82 (POLR3C ortholog) localizes to the nucleus, associates with RNAP III-dependent gene loci (tRNA and 5S rRNA genes), and interacts with C34 as a binding partner; knock-down of C82 by RNAi significantly reduced tRNA and 5S rRNA levels and caused death of procyclic T. brucei. The C31 subunit (RPC32 ortholog) was not detected as an interacting partner in trypanosomatids, unlike in yeast/vertebrates. RNAi knockdown with RNA quantification, chromatin immunoprecipitation (ChIP), tandem affinity purification (TAP) mass spectrometry, nuclear localization by microscopy Parasitology Medium 39523652

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-alpha mediated cellular immunity. Biomaterials 151 19403166
2012 Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C82(OH)22 and its implication for de novo design of nanomedicine. Proceedings of the National Academy of Sciences of the United States of America 144 22949663
2006 Antioxidative function and biodistribution of [Gd@C82(OH)22]n nanoparticles in tumor-bearing mice. Biochemical pharmacology 113 16436273
2007 Bacteriochlorophyllide c C-8(2) and C-12(1) methyltransferases are essential for adaptation to low light in Chlorobaculum tepidum. Journal of bacteriology 79 17586634
2017 Inhibition of β-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82. The Journal of investigative dermatology 46 28807667
2011 Biosafety assessment of Gd@C82(OH)22 nanoparticles on Caenorhabditis elegans. Nanoscale 32 21541378
2015 Quantitative analysis of Gd@C82(OH)22 and cisplatin uptake in single cells by inductively coupled plasma mass spectrometry. Analytical and bioanalytical chemistry 31 25701412
2019 β-catenin signaling inhibitors ICG-001 and C-82 improve fibrosis in preclinical models of endometriosis. Scientific reports 26 31882904
2024 Rational Design of Dual-Functionalized Gd@C82 Nanoparticles to Relieve Neuronal Cytotoxicity in Alzheimer's Disease via Inhibition of Aβ Aggregation. ACS nano 19 38840269
2015 DNA polymerases κ and ζ cooperatively perform mutagenic translesion synthesis of the C8-2'-deoxyguanosine adduct of the dietary mutagen IQ in human cells. Nucleic acids research 13 26220181
2014 Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the nanoparticle [Gd@C82(OH)22]n: A systems biology study. Methods (San Diego, Calif.) 13 24440483
2014 Gd@C82(OH)22 nanoparticles constrain macrophages migration into tumor tissue to prevent metastasis. Journal of nanoscience and nanotechnology 13 24738346
2013 Metallofullerenol Gd@C₈₂(OH)₂₂ distracts the proline-rich-motif from putative binding on the SH3 domain. Nanoscale 13 23423582
2015 Structural analysis of human RPC32β-RPC62 complex. Journal of structural biology 11 26394183
2001 The C(8)-(2'-deoxy-beta-D-ribofuranoside) of 7-deazaguanine: synthesis and base pairing of oligonucleotides with unusually linked nucleobases. The Journal of organic chemistry 10 11348111
2021 Effects of Aqueous Dispersions of C60, C70 and Gd@C82 Fullerenes on Genes Involved in Oxidative Stress and Anti-Inflammatory Pathways. International journal of molecular sciences 8 34200169
2010 The C8-2'-deoxyguanosine adduct of 2-amino-3-methylimidazo[1,2-d]naphthalene, a carbocyclic analogue of the potent mutagen 2-amino-3-methylimidazo[4,5-f]quinoline, is a block to replication in vitro. Chemical research in toxicology 8 20377178
2018 Distance Measurement of a Noncovalently Bound Y@C82 Pair with Double Electron Electron Resonance Spectroscopy. Journal of the American Chemical Society 7 29860839
2011 An anti-tumor nanoparticle, [Gd@C82(OH)22]n, induces macrophage activation. Journal of nanoscience and nanotechnology 6 21449388
2010 Transmembrane delivery of aggregated [Gd@C82(OH)22]n nanoparticles. Journal of nanoscience and nanotechnology 6 21121366
2014 Unprecedented chemical reactivity of a paramagnetic endohedral metallofullerene La@C(s)-C82 that leads hydrogen addition in the 1,3-dipolar cycloaddition reaction. Journal of the American Chemical Society 3 25469552
2025 Venetoclax synergizes with Wnt/β-catenin inhibitor C-82 in acute myeloid leukemia by increasing the degradation of Mcl-1 protein. Cancer cell international 2 40442688
2023 Effects of Aqueous Dispersions of C60, C70, and Gd@C82 Fullerenes on DNA Oxidative Damage/Repair and Apoptosis in Human Embryonic Lung Fibroblasts. ACS biomaterials science & engineering 2 36821424
2020 6-Nitrochrysene-Derived C8-2'-Deoxyadenosine Adduct: Synthesis of Site-Specific Oligodeoxynucleotides and Mutagenicity in Escherichia coli. Chemical research in toxicology 2 31903755
2007 Calculations of the C2 fragmentation energies of higher fullerenes C80 and C82. Journal of molecular modeling 2 17588181
2024 Computational insights into Diels-Alder reactions of paramagnetic endohedral metallofullerenes: M@C82 (M = Sc, Y, La) and La@C72. Physical chemistry chemical physics : PCCP 1 39377172
2017 Synthesis of Oligodeoxynucleotides Containing a C8-2'-Deoxyguanosine Adduct Formed by the Carcinogen 3-Nitrobenzanthrone. Current protocols in nucleic acid chemistry 1 28628210
2026 Water-soluble gadolinium fullerenes Gd@C82-TEGs as a potential magnetic resonance imaging contrast agent. PloS one 0 41961832
2025 Noncovalent interactions and properties of host-guest systems based on C82/C82Gd bucky-balls and symmetry broken nanohoop TP-[11]CPP. The Journal of chemical physics 0 40035581
2024 Analyses of the essential C82 subunit uncovered some differences in RNA polymerase III transcription between Trypanosoma brucei and Leishmania major. Parasitology 0 39523652

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