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Showing POLR1G — PAF49 is a alias.

POLR1G

DNA-directed RNA polymerase I subunit RPA34 · UniProt O15446

Length
510 aa
Mass
55.0 kDa
Annotated
2026-06-10
32 papers in source corpus 10 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POLR1G (PAF49/RPA34/ASE-1; yeast A34.5) is an RNA polymerase I-associated subunit essential for rDNA transcription and cell viability in mammalian cells (PMID:15226435, PMID:37356716). It forms a TFIIF-related heterodimer with PAF53 (yeast A49) through a defined dimerization domain (residues 41-86), an interaction structurally conserved from yeast to mammals (PMID:22849406). Within this heterodimer POLR1G engages multiple components of the Pol I initiation machinery: it contacts the SL1 subunit TAF(I)48, the recruitment factor Rrn3, and the Pol I subunit PolR1B via a distinct 'arm' domain, with both the dimerization domain and the arm being required for transcription (PMID:15226435, PMID:25225125, PMID:37356716). Its association with Pol I is dynamically controlled — hypoacetylated heterodimer binds Pol I with higher affinity than the acetylated form (PMID:25225125), and cryo-EM of elongation complexes shows the heterodimer reversibly dissociates from the enzyme, coupling its occupancy to regulation of initiation and elongation (PMID:30913026). POLR1G localizes to the nucleolus through tandem basic amino acid stretches in its central and C-terminal regions and co-localizes with the initiation factor UBF at sites of rDNA transcription (PMID:9426281, PMID:18329376). Functionally it stabilizes PAF53 unidirectionally, such that its loss triggers PAF53 co-degradation, nucleolar stress, and p53 accumulation (PMID:37356716). STAT3 drives POLR1G transcription by binding its promoter directly, thereby potentiating Pol I-directed rRNA synthesis and tumor cell growth (PMID:36526675).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1997 High

    Established that the POLR1G ortholog is a bona fide Pol I-associated factor collectively essential for rRNA synthesis, rather than a dispensable copurifying protein.

    Evidence Yeast genetics with deletion mutants, in vitro Pol I purification, synthetic lethality with A14, and rescue by Pol II-driven pre-rRNA

    PMID:9121426

    Open questions at the time
    • Did not define the mammalian counterpart's direct contacts within Pol I
    • Mechanism of relieving rDNA topological constraints not resolved at molecular level
  2. 1997 Medium

    Placed human ASE-1/POLR1G at the physical sites of rDNA transcription and linked it to the initiation factor UBF.

    Evidence Indirect immunofluorescence across the cell cycle and in vitro UBF binding assay

    PMID:9426281

    Open questions at the time
    • UBF association shown in vitro only, not validated in cells
    • Functional consequence of UBF interaction untested
  3. 2004 High

    Demonstrated that mammalian PAF49 is functionally required for promoter-specific Pol I transcription and bridges to the SL1 initiation complex and PAF53.

    Evidence Co-IP, in vitro transcription with antibody inhibition rescued by recombinant protein, dominant-negative overexpression, and growth-dependent localization

    PMID:15226435

    Open questions at the time
    • Did not map the domains mediating each interaction
    • Did not establish how the heterodimer's activity is regulated
  4. 2008 Medium

    Defined the molecular determinant of POLR1G nucleolar targeting, answering how the subunit is concentrated at rDNA.

    Evidence Serial deletion, combinatorial point mutagenesis, and heterologous protein redirection assays with fluorescence microscopy

    PMID:18329376

    Open questions at the time
    • Did not identify the nucleolar binding partner(s) recognizing these basic stretches
    • Single lab
  5. 2012 Medium

    Mapped the conserved dimerization interface (residues 41-86) responsible for heterodimer assembly with PAF53.

    Evidence Deletion/substitution mutagenesis with co-IP readout and interspecific rescue between yeast and mammalian residues

    PMID:22849406

    Open questions at the time
    • Did not test how dimerization affects Pol I binding or transcription directly
    • In silico structural inference only
  6. 2014 Medium

    Revealed that POLR1G's engagement with Pol I is tunable, with acetylation state controlling binding affinity, and linked the heterodimer to Rrn3 recruitment.

    Evidence Co-IP, acetylation-state manipulation, binding affinity comparison, and Rrn3 interaction assays

    PMID:25225125

    Open questions at the time
    • Acetyltransferase/deacetylase enzymes not identified
    • Functional consequence of acetylation on transcription output not directly measured
  7. 2019 High

    Provided a structural mechanism: reversible dissociation of the A49-A34.5 heterodimer from elongating Pol I, with conformational consequences for the A12.2 domain, links heterodimer occupancy to transcription regulation.

    Evidence Cryo-EM of yeast Pol I elongation complexes at 3.2-3.4 Å with biochemical validation

    PMID:30913026

    Open questions at the time
    • Structures are of yeast complexes; mammalian states not resolved
    • Trigger controlling reversible dissociation in vivo unknown
  8. 2022 Medium

    Identified an upstream transcriptional input, showing STAT3 directly drives POLR1G expression to amplify rRNA synthesis and tumor growth.

    Evidence ChIP, RNA-seq, rescue assays, and in vitro/in vivo tumor growth experiments

    PMID:36526675

    Open questions at the time
    • Whether STAT3-POLR1G axis operates outside the cancer contexts tested unknown
    • Did not address other regulators of POLR1G transcription
  9. 2023 High

    Established mammalian POLR1G as essential and dissected the domains driving function, defining the PolR1B-interacting 'arm' as a therapeutic vulnerability in cancer cells.

    Evidence Auxin-inducible degron, domain deletion, co-IP, viability assays, and nucleolar stress (p53) readouts comparing normal and cancer cells

    PMID:37356716

    Open questions at the time
    • Structural basis of the arm-PolR1B contact not solved
    • Basis for selective cancer cell death versus normal cell arrest not fully resolved
  10. 2024 Low

    Assigned the Drosophila ortholog of POLR1G computationally, extending evolutionary conservation of the subunit.

    Evidence Remote homology detection, secondary structure prediction, and phylogenetic analysis

    PMID:38287926

    Open questions at the time
    • Computational only, no experimental functional validation
    • Drosophila ortholog function not tested
  11. 2025 Low

    Proposed that the intrinsically disordered, NLS-rich C-terminal domain of POLR1G participates in Nopp140-driven phase separation to form the nucleolar dense fibrillar component.

    Evidence IDR identification, condensate/phase-separation assays, and nucleolar localization studies (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Direct demonstration of POLR1G IDR phase behavior versus related proteins limited
    • Link between condensate formation and Pol I transcription untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How acetylation, reversible heterodimer dissociation, and nucleolar condensate dynamics are integrated to control Pol I transcription in mammalian cells remains unresolved.
  • No mammalian cryo-EM structure of the POLR1G-containing complex
  • Enzymes setting POLR1G acetylation state unidentified
  • Physiological signals coupling STAT3 induction to heterodimer assembly unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005730 nucleolus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953854 Metabolism of RNA 2
Partners
PAF53POLR1BRRN3STAT3TAF(I)48UBF
Complex memberships
PAF49-PAF53 heterodimer (A49-A34.5 subcomplex)RNA polymerase I

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 A34.5 (yeast ortholog of POLR1G) is a phosphoprotein that copurifies with RNA polymerase I. Cells lacking A34.5 produce a catalytically active but structurally modified Pol I that also lacks subunit A49 upon in vitro purification. A34.5 deletion has synthetic lethality with A14 deletion, rescued by expressing pre-rRNA from a Pol II promoter, demonstrating collective essentiality for rRNA synthesis. A34.5 becomes quasi-essential in strains lacking DNA topoisomerase I, suggesting a role in helping Pol I overcome topological constraints on rDNA. Yeast genetics (deletion mutants), in vitro purification, genetic epistasis, complementation with Pol II-driven pre-rRNA Molecular and cellular biology High 9121426
1997 Human ASE-1 (POLR1G) localizes to the fibrillar centres of the nucleolus during interphase (putative sites of rDNA transcription) and to nucleolus organizer regions of chromosomes during mitosis. ASE-1 co-localizes with the Pol I transcription initiation factor UBF/NOR-90 throughout the cell cycle and associates with UBF in vitro. Indirect immunofluorescence with antibodies to cloned ASE-1 regions, in vitro binding assay, immunoblot Chromosoma Medium 9426281
2004 Mouse PAF49 (ortholog of POLR1G) copurifies with a transcriptionally competent subpopulation of RNA Pol I and physically associates with Pol I as confirmed by co-immunoprecipitation. PAF49 interacts with PAF53 through its N-terminal segment. PAF49 also interacts with TAF(I)48 (48-kDa subunit of SL1), leading to co-immunoprecipitation of other SL1 components. Anti-PAF49 antibody severely impairs specific in vitro transcription from the mouse rRNA promoter, restored by recombinant PAF49. Overexpression of a PAF49 deletion mutant reduces pre-rRNA synthesis in vivo. PAF49 accumulates in the nucleolus of growing cells but disperses to nucleoplasm in growth-arrested cells. Co-purification, co-immunoprecipitation, in vitro transcription assay with antibody inhibition and rescue, dominant-negative overexpression, immunolocalization Molecular and cellular biology High 15226435
2008 Nucleolar targeting of PAF49 (POLR1G) requires amino acids 199-338. Serial deletion and combinatorial point mutation analyses showed that tandem arrays of basic amino acid stretches (BS1-6) within the central and C-terminal regions cooperatively confer nucleolar localization. Appending these basic stretches in tandem to a heterologous protein (IRF-3) is sufficient to redirect it to the nucleolus, overriding an intrinsic nuclear export sequence. Serial deletion analysis, combinatorial point mutagenesis, heterologous protein targeting assay, fluorescence microscopy Biochemical and biophysical research communications Medium 18329376
2012 Mammalian PAF49 (POLR1G) and PAF53 are orthologs of yeast A34.5 and A49 and form a heterodimer analogous to the yeast TFIIF-related subcomplex. Deletion mutagenesis identified amino acids 41-86 of PAF49 as sufficient for heterodimerization with PAF53. Substitution of amino acids 52-98 of yeast A34.5 with mammalian PAF49 residues 41-86 enabled interspecific heterodimerization with mouse PAF53, confirming structural conservation of the dimerization domain. Deletion and substitution mutagenesis, co-immunoprecipitation, in silico structural analysis Biochemistry Medium 22849406
2014 The association of the PAF49/PAF53 heterodimer with Pol I is regulated: hypoacetylated PAF49 heterodimer binds Pol I with greater affinity than acetylated heterodimer. PAF49 is acetylated on multiple sites, but acetylation state does not affect heterodimerization. The PAF49/PAF53 heterodimer also interacts with Rrn3, suggesting a role in facilitating Rrn3 recruitment to Pol I for transcription initiation. Co-immunoprecipitation, acetylation state analysis, binding affinity comparison, interaction assay with Rrn3 Gene Medium 25225125
2019 Cryo-EM structures of yeast Pol I elongation complexes at 3.2-3.4 Å reveal that most GMPCPP-bound complexes lack the A49-A34.5 (POLR1G ortholog) heterodimer and adopt a Pol II-like conformation. In the absence of A49-A34.5, the A12.2 C-terminal domain occupies a previously unobserved position at the A135 surface. Biochemical data support a model in which reversible binding of the A49-A34.5 heterodimer contributes to regulation of Pol I transcription initiation and elongation. Cryo-electron microscopy (3.2-3.4 Å), biochemical analysis eLife High 30913026
2022 STAT3 activates RPA34 (POLR1G) gene transcription by directly binding the RPA34 promoter, as shown by ChIP assay, enhancing occupancy of Pol II transcription machinery at the RPA34 promoter. Increased RPA34 expression in turn enhances recruitment of the Pol I transcription machinery to the rDNA promoter and potentiates Pol I-directed transcription and tumor cell growth in vitro and in vivo. ChIP assay, RNAseq, rescue assays, in vitro and in vivo tumor growth experiments British journal of cancer Medium 36526675
2023 Mammalian PAF49 (POLR1G) is essential for rDNA transcription and cell division. Auxin-induced degradation of PAF49 induces nucleolar stress and p53 accumulation. Degradation of PAF49 leads to co-degradation of its binding partner PAF53, but not vice versa, revealing a unidirectional co-stabilization relationship. The dimerization domain of PAF49 and an 'arm' domain that interacts with PolR1B are both required for rDNA transcription. Disrupting the PAF49–PolR1B interaction inhibits Pol I transcription in normal and cancer cells, causing arrest of normal cells and death of cancer cells. Auxin-inducible degron system, domain deletion analysis, co-immunoprecipitation, cell growth and viability assays, nucleolar stress readouts (p53 accumulation) The Journal of biological chemistry High 37356716
2024 CG11076 was identified as the Drosophila melanogaster ortholog of Rpa34/POLR1G by remote homology detection and secondary structure analysis showing high predicted structural conservation, confirmed by phylogenetic analysis. Remote homology detection, secondary structure prediction, phylogenetic analysis microPublication biology Low 38287926
2025 PAF49 (POLR1G) contains a C-terminal domain (CTD) that is intrinsically disordered and NLS-rich. Nopp140 concentrates this IDR of PAF49 and related proteins to form the dense fibrillar component (DFC) of the nucleolus as a liquid-liquid phase separated condensate that fosters rRNA modification. Identification of IDR in PAF49 CTD; condensate/phase separation assays; nucleolar localization studies (detailed methods in preprint) bioRxivpreprint Low

Source papers

Stage 0 corpus · 32 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 A34.5, a nonessential component of yeast RNA polymerase I, cooperates with subunit A14 and DNA topoisomerase I to produce a functional rRNA synthesis machine. Molecular and cellular biology 64 9121426
2007 Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation. International journal of cancer 44 17131345
1997 ASE-1: a novel protein of the fibrillar centres of the nucleolus and nucleolus organizer region of mitotic chromosomes. Chromosoma 40 9426281
2005 Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1 on the risk of basal cell carcinoma among Caucasians after age 50. Cancer detection and prevention 39 15936590
2004 Multiple protein-protein interactions by RNA polymerase I-associated factor PAF49 and role of PAF49 in rRNA transcription. Molecular and cellular biology 35 15226435
2019 The cryo-EM structure of a 12-subunit variant of RNA polymerase I reveals dissociation of the A49-A34.5 heterodimer and rearrangement of subunit A12.2. eLife 33 30913026
2006 Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study. BMC cancer 30 16817948
2014 SAD1, an RNA polymerase I subunit A34.5 of rice, interacts with Mediator and controls various aspects of plant development. The Plant journal : for cell and molecular biology 29 25404280
2004 A hypophosphorylated form of RPA34 is a specific component of pre-replication centers. Journal of cell science 28 15456845
1996 A novel substrate-binding pocket interaction restricts the specificity of the human NK cell-specific serine protease, Met-ase-1. Journal of immunology (Baltimore, Md. : 1950) 25 8666785
2008 A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a Danish prospective case-cohort study. BMC cancer 22 18289367
2006 Gene-environment interactions between smoking and a haplotype of RAI, ASE-1 and ERCC1 polymorphisms among women in relation to risk of lung cancer in a population-based study. Cancer letters 22 16690207
1996 Cloning and expression of the recombinant mouse natural killer cell granzyme Met-ase-1. Immunogenetics 22 8781119
1995 Expression of recombinant human Met-ase-1: a NK cell-specific granzyme. Biochemical and biophysical research communications 20 7503751
2015 Association and interaction of NFKB1 rs28362491 insertion/deletion ATTG polymorphism and PPP1R13L and CD3EAP related to lung cancer risk in a Chinese population. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 26563375
2023 Common variants of pro-inflammatory gene IL1B and interactions with PPP1R13L and POLR1G in relation to lung cancer among Northeast Chinese. Scientific reports 14 37147350
2014 Regulation of the association of the PAF53/PAF49 heterodimer with RNA polymerase I. Gene 12 25225125
2012 Characterization of the interactions of mammalian RNA polymerase I associated proteins PAF53 and PAF49. Biochemistry 12 22849406
2018 Different splicing isoforms of ERCC1 affect the expression of its overlapping genes CD3EAP and PPP1R13L, and indicate a potential application in non-small cell lung cancer treatment. International journal of oncology 10 29620255
2018 GLTSCR1, ATM, PPP1R13L and CD3EAP Genetic Variants and Lung Cancer Risk in a Chinese Population. Current medical science 10 30128886
2023 PAF49: An RNA Polymerase I subunit essential for rDNA transcription and stabilization of PAF53. The Journal of biological chemistry 8 37356716
2017 19p13.3-GADD45B common variants and 19q13.3-PPP1R13L and 19q13.3-CD3EAP in lung cancer risk among Chinese. Chemico-biological interactions 8 28870783
2013 Effects of PPP1R13L and CD3EAP variants on lung cancer susceptibility among nonsmoking Chinese women. Gene 8 23624123
2015 NFKB1 common variants and PPP1R13L and CD3EAP in relation to lung cancer risk in a Chinese population. Gene 7 25917613
2015 Genetic Polymorphisms in XRCC1, CD3EAP, PPP1R13L, XPB, XPC, and XPF and the Risk of Chronic Benzene Poisoning in a Chinese Occupational Population. PloS one 6 26681190
2022 STAT3 potentiates RNA polymerase I-directed transcription and tumor growth by activating RPA34 expression. British journal of cancer 5 36526675
2021 TP53 common variants and interaction with PPP1R13L and CD3EAP SNPs and lung cancer risk and smoking behavior in a Chinese population. Biomedical journal 4 35351459
2017 Association of PPP1R13L and CD3EAP polymorphisms with risk and survival of non-small cell lung cancer in Chinese non-smoking females. Oncotarget 4 29108262
2020 Interaction between common variants of MDM2 and PPP1R13L and CD3EAP and TP53 SNPs in relation to lung cancer risk among Chinese. Annals of translational medicine 3 32953734
2017 Exome-Wide Meta-Analysis Identifies Rare 3'-UTR Variant in ERCC1/CD3EAP Associated with Symptoms of Sleep Apnea. Frontiers in genetics 3 29093733
2008 Nucleolar targeting of proteins by the tandem array of basic amino acid stretches identified in the RNA polymerase I-associated factor PAF49. Biochemical and biophysical research communications 1 18329376
2024 Remote homology identification of the Drosophila melanogaster ortholog of the RNA Polymerase I subunit Rpa34/POLR1G. microPublication biology 0 38287926

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