Affinage

GTF3A

Transcription factor IIIA · UniProt Q92664

Length
365 aa
Mass
41.5 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GTF3A/TFIIIA is the founding assembly factor for RNA polymerase III transcription of 5S rRNA genes, functioning as a modular nine-zinc-finger protein whose fingers comprise ~80% of the protein mass and constitute the DNA-binding domain that spans the internal control region (ICR) of the 5S gene (PMID:2837652, PMID:6210149). The high-affinity DNA contact resides in the three N-terminal fingers, which bind the C-block of the ICR in the major groove with each finger contacting 4-5 base pairs and providing the majority of the binding free energy (PMID:9367756, PMID:1538401, PMID:8011622). The inter-finger TGEKP-type linkers actively confer DNA-binding specificity rather than merely tethering the fingers (PMID:8346014, PMID:9443960), and binding bends the 5S DNA helix into a hairpin-like configuration (PMID:2927394, PMID:2011525). Upon assembling on the ICR, TFIIIA recruits TFIIIC, which then loads TFIIIB—the sole pol III initiation factor—to position polymerase for repeated transcription cycles, with TFIIIA and TFIIIC serving as assembly factors rather than initiation factors per se (PMID:2404611, PMID:1517247). Maximal transcriptional activation requires a C-terminal, position-dependent activation domain lying outside the zinc-finger region, whose function depends on its distance (length, not sequence) from the DNA-binding domain (PMID:2837652, PMID:8246967); in yeast this corresponds to a C-terminal hydrophobic segment essential for activity but not DNA binding (PMID:9418889), and finger 1 is required for TFIIIC incorporation independently of DNA binding (PMID:17626045). The sole essential function of TFIIIA is 5S rRNA gene transcription, established genetically in yeast (PMID:7568129). Beyond transcription, TFIIIA stores newly made 5S rRNA in cytoplasmic 7S RNPs, binding RNA through a distinct set of central fingers (4-7, with finger 6 specialized) via recognition of 5S RNA tertiary structure rather than primary sequence; 5S RNA binding masks the zinc-finger nuclear localization signals, retaining the 7S RNP in the cytoplasm (PMID:1423623, PMID:7689146, PMID:9874245, PMID:15146977). TFIIIA participates in developmental regulation of the two 5S gene families: differential nucleosome positioning and competition with histone H1 selectively repress oocyte-type genes (PMID:9737930, PMID:7870575), and CK2 phosphorylation of serine-16 converts TFIIIA into a repressor specific for oocyte-type but not somatic-type genes (PMID:14993284). In human cells, GTF3A directly drives transcription of the 5S pseudogene RNA5SP141, an endogenous RIG-I agonist; loss-of-function GTF3A mutations diminish RNA5SP141 expression, abrogate RIG-I activation, and impair cell-intrinsic antiviral responses to HSV-1 (PMID:36399538).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1984 High

    Establishing that a single cloned polypeptide is both a 5S transcription initiation factor and a 5S RNA-storage protein defined TFIIIA's dual nucleic-acid-binding role and linked its abundance to oogenesis.

    Evidence cDNA cloning, in vitro transcription assays, and developmental expression analysis in Xenopus

    PMID:6210149

    Open questions at the time
    • Did not resolve which protein regions mediate DNA versus RNA binding
    • Mechanism of transcription stimulation undefined
  2. 1984 High

    Quantifying TFIIIA across development showed its concentration changes 10^5-fold while its structure and activity remain constant, framing 5S gene regulation as a concentration- and chromatin-dependent problem.

    Evidence Quantitative immunoassay, CNBr peptide analysis, and in vitro 5S transcription across Xenopus developmental stages

    PMID:6206067

    Open questions at the time
    • Did not establish whether concentration alone dictates expression pattern
    • No mechanism for differential oocyte/somatic gene regulation
  3. 1987 Medium

    Overexpression showed that excess TFIIIA only transiently activates oocyte-type genes, proving additional developmental inactivation mechanisms operate beyond factor abundance.

    Evidence Synthetic TFIIIA mRNA injection into Xenopus eggs with transcription analysis through development

    PMID:3664642

    Open questions at the time
    • Identity of the inactivation mechanism unresolved at the time
    • No molecular basis for oocyte-specific silencing
  4. 1988 High

    Deletion mapping defined TFIIIA's modular architecture—nine fingers as the DNA-binding/ICR-spanning domain plus a separable C-terminal activation region—separating recognition from stimulation.

    Evidence In vitro transcription/translation of deletion mutants in cell-free transcription assays

    PMID:2837652

    Open questions at the time
    • Did not define which downstream factor the activation domain contacts
    • Per-finger contributions to DNA contact unresolved
  5. 1990 High

    Reconstitution placed TFIIIA and TFIIIC as assembly factors whose role is to load TFIIIB, the sole pol III initiation factor, refining the hierarchy of the 5S transcription apparatus.

    Evidence In vitro transcription reconstitution with binary and ternary complex analysis in S. cerevisiae

    PMID:2404611

    Open questions at the time
    • Molecular contacts between TFIIIA and TFIIIC not mapped
    • Did not address developmental gene selectivity
  6. 1990 Medium

    Structural imaging and circular-permutation assays showed TFIIIA bends 5S DNA ~60-65 degrees into a hairpin, revealing that binding remodels promoter geometry.

    Evidence Electron spectroscopic imaging and circular permutation gel shift assays of TFIIIA-5S DNA complexes

    PMID:2011525 PMID:2927394

    Open questions at the time
    • Functional consequence of bending for transcription not isolated
    • Single-method structural inference
  7. 1991 Medium

    Mapping TFIIIA-5S RNA contacts to the RNA's tertiary fold (hinge/loop E, helices IV-V) established that RNA recognition reads three-dimensional structure rather than sequence, distinguishing it from DNA binding.

    Evidence Hydroxyl radical footprinting, missing-nucleoside experiments, and trans-DDP crosslinking within the 7S RNP

    PMID:1939152 PMID:2602112

    Open questions at the time
    • Did not assign individual fingers to specific RNA contacts
    • Functional role of RNP storage in regulation unclear
  8. 1991 Medium

    Identifying NLSs within the zinc fingers and showing 5S RNA binding masks them gave a mechanism for cytoplasmic retention of the 7S RNP.

    Evidence NLS mapping by nuclear import assays, importin alpha variant analysis, and in vitro binding in Xenopus

    PMID:15146977

    Open questions at the time
    • Did not quantify how much storage RNP contributes to feedback regulation
    • Single lab
  9. 1992 High

    Subdomain dissection localized high-affinity sequence-specific DNA binding to fingers 1-3 at the C-block and the principal RNA-binding capacity to fingers 4-7, partitioning the two nucleic-acid functions across the protein.

    Evidence Purified finger-subdomain footprinting/gel shift, systematic finger-combination analysis, proteolytic and nuclease footprinting in vitro and in oocytes

    PMID:1423623 PMID:1538401 PMID:1827669 PMID:7689146

    Open questions at the time
    • Atomic-level base contacts not yet resolved
    • Why finger 6 behaves uniquely for RNA not explained
  10. 1992 Medium

    Detecting TFIIIA-TFIIIC complex formation, with higher TFIIIC affinity for somatic-type than oocyte-type TFIIIA-DNA complexes, provided a biochemical handle on developmental gene discrimination.

    Evidence UV crosslinking, gel mobility shift, and B-block DNA affinity purification in Xenopus

    PMID:1517247

    Open questions at the time
    • Structural basis of differential TFIIIC affinity unknown
    • Did not identify TFIIIA residues contacting TFIIIC
  11. 1992 Medium

    Fine mapping of sequence-dependent contacts to box C and the intermediate element, with non-coding-strand dominance, defined the high-affinity TFIIIA recognition sequence.

    Evidence Missing-nucleoside, hydroxyl radical footprinting, point mutagenesis, and SAAB selection

    PMID:1404361 PMID:8011622

    Open questions at the time
    • Individual finger-to-base assignments incomplete
    • Single lab
  12. 1993 High

    In vivo single-finger mutagenesis assigned discrete roles—fingers 1-3, 8, 9 for activation; finger 6 for feedback regulation—and revealed gain-of-function variants that derepress silent oocyte genes.

    Evidence Single His-to-Asn substitutions, mRNA microinjection in Xenopus embryos, and in vivo/in vitro transcription assays

    PMID:8336715

    Open questions at the time
    • Molecular target of the C-terminal fingers in activation unresolved
    • Mechanism of finger-6 feedback sensitivity not defined
  13. 1993 Medium

    Defining a 14-residue C-terminal activation domain whose function depends on spacer length rather than sequence showed activation is a position-dependent, distance-tuned event separate from DNA recognition.

    Evidence Bacterial expression of MBP-TFIIIA deletion/substitution/insertion mutants with in vitro transcription in depleted extract

    PMID:8246967

    Open questions at the time
    • Did not identify the factor contacted by the activation domain
    • Spacer-length geometry not structurally explained
  14. 1993 Medium

    Linker-substitution experiments demonstrated that inter-finger linkers actively determine DNA-binding specificity and affinity, elevating linkers from passive tethers to functional elements.

    Evidence Linker substitution mutagenesis with DNA binding assays on N-terminal three-finger constructs (and later TFIIIA/p43 linker exchanges)

    PMID:8346014 PMID:9443960

    Open questions at the time
    • Generalization across all nine fingers untested
    • Effect on full-length complex assembly not measured
  15. 1995 High

    Genetic ablation in yeast proved that 5S rRNA gene transcription is TFIIIA's only essential function, bounding its physiological role.

    Evidence Genetic complementation with a TFIIIA-independent 5S construct in TFIIIA-null yeast plus in vitro confirmation

    PMID:7568129

    Open questions at the time
    • Did not exclude nonessential roles such as RNA storage
    • Yeast result may not capture metazoan-specific functions
  16. 1995 Medium

    Human TFIIIA was shown to prevent nucleosomal repression of the 5S gene only if it binds the ICR before chromatin assembly, framing TFIIIA-nucleosome competition as a kinetic switch for gene activity.

    Evidence Nucleosome reconstitution with purified histones, in vitro transcription, and DNase I footprinting on the human 5S gene

    PMID:7870575

    Open questions at the time
    • Did not address how preferential positioning arises in cells
    • No factor-recruitment readout
  17. 1998 Medium

    Nucleosome positioning—not histone acetylation—and competition with histone H1 were shown to discriminate oocyte from somatic 5S genes, supplying the long-sought molecular basis for selective oocyte gene repression.

    Evidence Nucleosome reconstitution with controlled translational positioning and TFIIIA/H1 binding competition assays

    PMID:9488430 PMID:9737930

    Open questions at the time
    • In vivo validation of positioning differences not established here
    • Did not connect to TFIIIA modifications
  18. 1997 High

    The NMR structure of the three N-terminal fingers on 5S DNA gave atomic-resolution rules for recognition—novel Trp/Arg base contacts and linker ordering upon binding—explaining the high-affinity C-block grip.

    Evidence NMR solution structure determination with mutagenesis validation

    PMID:9367756

    Open questions at the time
    • Structure of fingers 4-9 on DNA not solved
    • Did not visualize the RNA-bound state
  19. 2004 Medium

    Identifying CK2 phosphorylation of serine-16 as a switch that converts TFIIIA into an oocyte-gene-specific repressor without altering nucleic-acid binding linked a post-translational modification to gene-class discrimination.

    Evidence Ser16 substitution mutants with in vitro transcription in immunodepleted extract, in vivo Xenopus transcription, and template exclusion assays

    PMID:14993284

    Open questions at the time
    • The inactive factor recruited into the repressive complex not fully identified
    • Single lab; physiological regulation of CK2 toward TFIIIA unclear
  20. 2005 Medium

    Kinetic analysis of stabilizing mutations, including an intercalation mechanism for L148F, established that transcriptional activation depends on the lifetime (kinetic stability) rather than thermodynamic affinity of the TFIIIA-DNA complex.

    Evidence Site-directed mutagenesis, quantitative gel shift, assembly/dissociation kinetics, and yeast transcription assays

    PMID:15888446

    Open questions at the time
    • Generality across natural TFIIIA variants untested
    • Link between complex lifetime and TFIIIC recruitment not directly measured
  21. 2022 High

    Human loss-of-function genetics revealed a non-canonical role: GTF3A drives transcription of the RNA5SP141 pseudogene, an endogenous RIG-I ligand required for cell-intrinsic antiviral immunity against HSV-1.

    Evidence ChIP-seq for TFIIIA targets, patient fibroblasts and GTF3A gene-edited cells, innate immune and viral replication assays

    PMID:36399538

    Open questions at the time
    • How RNA5SP141 transcription is regulated relative to canonical 5S genes unclear
    • Whether this immune role is conserved beyond human cells unaddressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TFIIIA integrates DNA-binding kinetics, the C-terminal activation domain, and TFIIIC recruitment into a unified activation mechanism, and how its 5S-transcription role connects mechanistically to RNA5SP141-driven antiviral signaling, remain unresolved.
  • No structural model of the full TFIIIA-DNA-TFIIIC assembly
  • Direct partner contacted by the activation domain unidentified
  • Mechanistic link between canonical 5S transcription and RNA5SP141 antiviral function unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4 GO:0140223 general transcription initiation factor activity 2
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 2 R-HSA-168256 Immune System 1
Partners
CSNK2A1KPNA1KPNA2RPL5TFIIIC
Complex memberships
5S rRNA gene pol III preinitiation complex7S RNP (TFIIIA-5S rRNA storage particle)

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 In S. cerevisiae, TFIIIB is the sole transcription initiation factor for RNA pol III; TFIIIA and TFIIIC function only as assembly factors required to load TFIIIB onto the 5S rRNA gene promoter. TFIIIB alone correctly positions pol III for repeated transcription cycles. In vitro transcription reconstitution; binary and ternary complex analysis on SUP4 tRNA and 5S rRNA genes Cell High 2404611
1984 TFIIIA is a 38,500 Da polypeptide required for initiation of 5S RNA gene transcription in Xenopus oocytes and also stabilizes 5S RNA in ribonucleoprotein complexes. Levels of TFIIIA and its mRNA are coordinately regulated during oogenesis and embryonic development. cDNA cloning, in vitro transcription assays, developmental expression analysis Cell High 6210149
1988 TFIIIA has a modular structure: the nine zinc fingers (comprising 80% of protein mass) constitute the DNA-binding domain that spans the 5S RNA gene internal control region (ICR), with the C-terminus oriented toward the 5' end and N-terminus toward the 3' end. A region near the C-terminus (~19 amino acids), outside the DNA-binding domain, is critical for maximal transcription activation. In vitro transcription/translation of deletion mutants; cell-free transcription assays Molecular and cellular biology High 2837652
1992 Most or all of the nine zinc fingers of TFIIIA participate in both 5S DNA and 5S RNA binding, but minimal finger sets sufficient for DNA versus RNA recognition differ. RNA binding relies mainly on structural/tertiary information in 5S RNA, not primary sequence, and occurs via a fundamentally different mechanism than DNA binding. Systematic zinc finger combination analysis in Xenopus oocytes; in vitro binding assays Cell High 1423623
1997 NMR solution structure of the three N-terminal zinc fingers of TFIIIA bound to cognate 5S DNA: all three fingers bind in the major groove, each contacting 4-5 base pairs. Novel base contacts involve tryptophan at position +2 (finger 1) and arginine at position +10 (finger 3). The TGEKP(N) linkers, flexible in free protein, become ordered upon DNA binding. Protein-protein contacts between adjacent fingers contribute to high-affinity binding. NMR solution structure determination; mutagenesis validation Journal of molecular biology High 9367756
1992 The first three zinc fingers of TFIIIA bind the C-block region (+80 to +92) of the 5S RNA gene ICR with high affinity (Kd = 5.6 nM vs 2.2 nM for full-length TFIIIA), providing the majority of free energy of TFIIIA-DNA binding. Fingers 1+2 or fingers 2+3+4 alone do not exhibit sequence-specific binding. Bacterial expression and purification of finger subdomains; DNase I footprinting; methylation interference; gel shift assays Journal of molecular biology High 1538401
1993 Linker sequences connecting zinc fingers 1-3 of TFIIIA play an active role in DNA binding; insertion of heterologous linkers abolishes binding, and substitution of individual linker amino acids reduces binding up to 24-fold. Linker substitution mutagenesis; DNA binding assays with N-terminal three-finger constructs Nucleic acids research Medium 8346014
1992 TFIIIA interacts with 5S DNA across three distinct regions (A-box, intermediate element, C-box). Throughout the binding site, strongest contacts are with the non-coding strand. TFIIIA wraps around DNA in the major groove for one helical turn at boxes A and C and lies on one side of the helix at the intermediate element. Missing-nucleoside experiment; hydroxyl radical footprinting Journal of molecular biology Medium 1404361
1990 TFIIIA bends the 5S DNA helix into a hairpin-shaped configuration upon binding, as directly visualized by high-resolution analytical electron spectroscopic imaging. Electron spectroscopic imaging of TFIIIA-5S DNA complexes Molecular and cellular biology Medium 2927394
1990 TFIIIA induces DNA bending of approximately 60-65° at the internal promoter of the 5S gene (measured by circular permutation gel shift assay), with conformational flexibility allowing detection of a second conformation (~25-30° bend) under low ionic strength conditions. Circular permutation gel shift assay under varying ionic conditions Nucleic acids research Medium 2011525
1991 Hydroxyl radical footprinting and missing-nucleoside experiments show that TFIIIA interacts extensively with 5S rRNA, particularly along the arm composed of helix IV-loop E-helix V, with critical contact sites within loop E. Hydroxyl radical footprinting; missing-nucleoside experiment using Fe[EDTA]/H2O2 and bis-phenanthroline-copper The Journal of biological chemistry Medium 1939152
1991 Trans-diamminedichloroplatinum(II) crosslinking of TFIIIA to 5S rRNA within the 7S RNP identifies contact sites exclusively in the hinge region at the junction of the three helical domains (nucleotides 9-21 and 54-71), demonstrating that 3D folding of 5S rRNA is crucial for TFIIIA recognition. Chemical crosslinking with trans-DDP followed by RNA fragment identification Nucleic acids research Medium 2602112
1992 The primary DNA-binding region of TFIIIA is in zinc fingers 1-3 (N-terminus), while the primary RNA-binding region is in zinc fingers 4-7 (C-terminal of the repeat region). Finger 6 exhibits RNA-binding characteristics distinct from the other eight modules. Proteolytic footprinting shows trypsin cleaves TFIIIA differently when bound to oocyte vs. somatic 5S RNA, revealing different tightly-binding sites for 5S RNA vs. 5S DNA. Proteolytic footprinting with trypsin/chymotrypsin; immunoblotting with N-terminal antibody; gel electrophoresis Molecular and cellular biology Medium 7689146
1992 The primary 5S RNA-binding region in TFIIIA is zinc fingers 4-7 (C-terminal of the repeat region); fingers 8 and 9 interact specifically with the distal portion of helix V of 5S RNA. In contrast, fingers 1-3 are the tightest DNA-binding site. RNP reconstitution with intact and C-terminally truncated TFIIIA; RNase protection assays with cobra venom nuclease and alpha-sarcin Nucleic acids research Medium 1827669
1998 Within 5S RNA, three regions in finger 6 of TFIIIA are critical for RNA binding: aromatic character of tryptophan 177 is essential for RNA recognition, loop A nucleotides 10-13 (three of four are vital), and specific phosphate backbone contacts in helix V. A minimal TFIIIA-binding RNA includes truncated helices I and II, helix V, and structurally intact loops A and E. Permutation analysis; alanine-scanning mutagenesis of TFIIIA finger 6; ethylation interference assays; deletion analysis of 5S RNA European journal of biochemistry Medium 9874245
1987 TFIIIA binds to different structural domains in 5S RNA versus the 5S RNA gene. Mutations altering helices IV and V of 5S RNA decrease TFIIIA binding to form 7S RNPs, while some mutations that abolish efficient transcription do not affect 7S RNP formation. Linker substitution mutagenesis of 5S RNA gene; gel mobility shift assays for 7S particle formation Molecular and cellular biology Medium 3431548
1984 TFIIIA levels are ~10^12 molecules/oocyte early in oogenesis, declining 100-400-fold by the unfertilized egg stage, and then further 10^5-fold per cell through development. Somatic cells contain ~10^4 molecules/cell. The protein retains identical structural and functional properties (by CNBr peptide analysis and 5S transcription) at all developmental stages. Quantitative immunoassay with anti-TFIIIA antibody; CNBr peptide analysis; in vitro 5S transcription The Journal of biological chemistry High 6206067
1991 TFIIIA has two nuclear localization signals residing in the zinc finger region, which is the same region in direct contact with 5S rRNA in the 7S RNP. Only importin alpha1 and importin alpha2 interact specifically with TFIIIA and are expressed in a pattern similar to TFIIIA during Xenopus embryogenesis. 5S rRNA binding masks the NLS, retaining the 7S RNP in the cytoplasm. NLS mapping by in vivo and in vitro nuclear import assays; importin alpha variant analysis; in vitro binding assays European journal of cell biology Medium 15146977
1991 During Xenopus oogenesis, 5S RNA stored in 7S RNP with TFIIIA in the cytoplasm can transition to association with ribosomal protein L5 (5S RNP) for nuclear accumulation and ribosome assembly. Nucleotides 11-108 of 5S RNA are required for formation of complexes with either TFIIIA or L5 and for nuclear accumulation. Microinjection of labeled 5S RNA; immunoprecipitation; in situ hybridization; sucrose gradient fractionation Developmental biology Medium 1995392
1993 A 14-amino acid region near the C-terminus of TFIIIA (outside the zinc finger domain) constitutes a position-dependent transcriptional activation domain. Its activity is sensitive to distance from the DNA-binding domain: deletion of the 8 spacer amino acids between the activation domain and the last zinc finger abolishes transcriptional activity, while diverse amino acid substitutions in the spacer restore activity, indicating length rather than sequence is critical. Bacterial expression of MBP-TFIIIA deletion/substitution/insertion mutants; in vitro transcription in TFIIIA-depleted extract Molecular and cellular biology Medium 8246967
1995 The only essential function of yeast TFIIIA is transcription of 5S rRNA genes. Yeast cells completely devoid of TFIIIA can survive if provided 5S rRNA from a TFIIIA-independent hybrid promoter construct, demonstrating no other essential cellular role for TFIIIA. Genetic complementation; in vivo and in vitro transcription in TFIIIA-null yeast Proceedings of the National Academy of Sciences of the United States of America High 7568129
1992 Yeast TFIIIA has nine zinc finger motifs but is extensively diverged from Xenopus TFIIIA in sequence. A C-terminal truncated form containing 4.5 zinc fingers retains DNA binding but loses transcription activity. The TFIIIA gene is single-copy and essential for cell viability in yeast. Cloning and in vitro transcription/translation; DNA binding assays; genetic viability tests The Journal of biological chemistry Medium 1737784
1998 In yeast TFIIIA, a hydrophobic leucine-rich segment (residues 352-359, NGLNLLLN) at the C-terminal end of the unique 81-amino acid inter-finger domain (between zinc fingers 8 and 9) is essential for transcription factor activity but not DNA binding. Hydrophobic residues L343, L347, L354, L356, L357, and L358 are particularly important. These likely mediate a protein-protein interaction with another transcriptional machinery component. Internal deletion and site-directed mutagenesis; in vitro transcription assays; yeast viability assays Molecular and cellular biology Medium 9418889
1992 Xenopus TFIIIC (containing an 85-kDa subunit that binds the B-block) interacts with the TFIIIA·5S DNA complex. TFIIIC has 5-fold higher affinity for the somatic-type 5S RNA gene TFIIIA complex than for the oocyte-type gene complex. Mutations near the 5' boundary of the TFIIIA binding site alter TFIIIA footprint and reduce TFIIIA-mutant complexes' affinity for TFIIIC. UV crosslinking; gel mobility shift assays; B-block DNA affinity purification The Journal of biological chemistry Medium 1517247
1993 In vivo analysis of single zinc finger mutations in Xenopus TFIIIA: fingers 1, 2, 3 are important for transcriptional activation; fingers 5 and 7 are dispensable; fingers 8 and 9 are critical (mutation abolishes activation). Mutations in finger 4 or 6 produce hyperactive TFIIIA, activating normally-silent oocyte-type 5S RNA genes. Finger 6 disruption reduces susceptibility to feedback inhibition by 5S RNA, increasing TFIIIA availability for transcription complex formation. Single His-to-Asn substitutions in each zinc finger; mRNA microinjection in Xenopus embryos; in vivo and in vitro transcription assays Molecular and cellular biology High 8336715
1994 Sequence-dependent TFIIIA contacts on 5S DNA are concentrated within box C (positions 80-91), where GC base pairs at positions 81, 85, 86, 89, and 91 significantly reduce TFIIIA binding when substituted. Interaction with the intermediate element is localized to two GC base pairs at positions 70 and 71. SAAB selection confirmed that the wild-type sequence from +79 to +92 is the highest-affinity TFIIIA binding sequence. Point mutagenesis; quantitative gel mobility shift assays; SAAB selection-amplification assay Biochemistry Medium 8011622
1998 Nucleosome translational position—not histone acetylation—determines TFIIIA's ability to bind nucleosomal 5S rRNA genes. Unfavorable translational positions prevent TFIIIA binding even in the presence of histone acetylation. Nucleosome reconstitution on overlapping gene fragments; binding assays with TFIIIA Molecular and cellular biology Medium 9488430
1998 Differential nucleosome positioning on oocyte vs. somatic 5S rRNA genes determines relative TFIIIA vs. histone H1 binding. In competition assays, TFIIIA preferentially binds somatic-type nucleosomes while H1 preferentially binds oocyte-type nucleosomes, excluding TFIIIA; this provides a molecular mechanism for selective H1-mediated repression of oocyte 5S RNA genes in somatic cells. Unambiguous nucleosome mapping; TFIIIA and H1 binding competition assays on reconstituted nucleosomes Journal of molecular biology Medium 9737930
2004 Xenopus TFIIIA is phosphorylated on serine-16 by CK2. A phosphomimetic S16E mutation does not affect DNA or RNA binding but specifically abolishes transcription of oocyte-type (but not somatic-type) 5S rRNA genes in vitro and in vivo. The S16E mutant binds oocyte-type genes and recruits at least one other pol III transcription factor into an inactive complex, suggesting phosphorylation by CK2 converts TFIIIA into an active repressor of oocyte-type genes. Alanine/glutamic acid substitutions at Ser16; in vitro transcription in immunodepleted nuclear extract; in vivo transcription in Xenopus embryos; template exclusion assays Molecular and cellular biology Medium 14993284
1998 Linker substitutions between TFIIIA zinc fingers 1-3 (replacing TGEKP-type with p43-type linkers) cause a 50-fold reduction in DNA-binding specificity and 8-fold reduction in affinity, without affecting 5S RNA binding by N-terminal fingers. This demonstrates that zinc finger linkers specifically facilitate DNA binding specificity rather than RNA binding. Linker amino acid exchanges between TFIIIA and p43; quantitative DNA and RNA binding competition assays Nucleic acids research Medium 9443960
2004 Zn-TFIIIA has an average Zn2+ dissociation constant of ~10^-7 M. Cd2+ and Pb2+ displace Zn2+ and disrupt TFIIIA binding to its cognate 5S rDNA. TFIIIA's Zn2+ reactivity is substantially reduced when the protein is bound to its cognate DNA (ICR), indicating DNA binding protects zinc coordination. Metal binding stoichiometry; ligand competition kinetics (zincon, PAR, H2KTSM2); NMR of isolated finger domains Journal of inorganic biochemistry Medium 15134923
2005 Four mutations in Xenopus TFIIIA increase TFIIIA-5S rDNA complex stability; three primarily by decreasing the dissociation rate. The L148F substitution acts via an intercalation mechanism: a planar side chain at position 148 intercalates between adjacent base pairs in the intermediate element, producing very stable TFIIIA-DNA complexes through a slow conformational change. Transcriptional activation is thus dependent primarily on the kinetic (lifetime) rather than thermodynamic stability of the TFIIIA-DNA complex. Site-directed mutagenesis; quantitative gel shift; kinetic analysis of assembly/dissociation; yeast transcription activation assays The Journal of biological chemistry Medium 15888446
2007 In yeast TFIIIA, zinc fingers 1 and 7 have essential roles beyond DNA binding: finger 1 residues (identified by alanine-scanning) are required for TFIIIC incorporation into the TFIIIA-DNA complex without affecting DNA binding. Disruption of fingers 4, 5, or 6 has minimal effect on DNA binding and transcription factor activity. Disruption of both fingers 8 and 9 abolishes activity, while disruption of either alone retains activity. Zinc-finger disruption mutations; alanine-scanning mutagenesis; in vitro transcription; in vivo yeast viability assays Nucleic acids research Medium 17626045
1989 5-azidodeoxyuridine photocrosslinking to TFIIIA in 5S DNA complexes provides direct evidence that TFIIIA contacts the major groove. Over 90% of crosslinking from T residues occurs at positions 84 (non-coding strand) and 88 (coding strand). V8 protease digestion and amino acid sequencing of crosslinked peptides identified zinc finger 2 plus the finger 2-3 linker as contacting position 84, and the finger 5-6 linker region as contacting an upstream site. Site-specific photocrosslinking with 5-azidodeoxyuridine; V8 protease digestion; amino acid sequence analysis of crosslinked peptides The Journal of biological chemistry Medium 1885581
1989 TFIIIA mRNA contains internal sequences in the 3' untranslated region that dramatically destabilize RNA in Xenopus embryos, reducing the half-life of CAT reporter mRNA from 2.5 hours to less than 30 minutes after insertion of the TFIIIA sequence, suggesting a site for endonuclease action. Injection of synthetic capped/polyadenylated RNA chimeras into fertilized Xenopus eggs; stability measurement by Northern blot Development Medium 2458900
1987 Elevated TFIIIA concentration in developing Xenopus embryos (achieved by injection of synthetic TFIIIA mRNA) transiently activates oocyte-type 5S RNA genes from mid-blastula through mid-gastrulation, but these genes are subsequently inactivated by neurulation even in the presence of excess TFIIIA—showing that TFIIIA concentration alone does not determine the final pattern of 5S gene expression and that additional inactivation mechanisms exist. Synthetic mRNA injection into fertilized Xenopus eggs; transcription analysis during development Cell Medium 3664642
1995 Human TFIIIA alone is sufficient to prevent nucleosomal repression of the homologous human 5S rRNA gene in a fully defined in vitro system using purified core histones. Pre-binding of hTFIIIA to the ICR before nucleosome reconstitution maintains transcriptional competence. However, pre-formed nucleosomes covering the ICR preclude subsequent hTFIIIA binding. Nucleosome reconstitution with purified core histones + pectin; in vitro transcription; DNase I footprinting Nucleic acids research Medium 7870575
2022 Loss-of-function mutations in human GTF3A (encoding TFIIIA) impair HSV-1-induced innate immune responses. TFIIIA directly regulates transcription of the 5S ribosomal RNA pseudogene 141 (RNA5SP141), an endogenous RIG-I ligand. GTF3A mutant patient fibroblasts and gene-edited cells show diminished RNA5SP141 expression and abrogated RIG-I activation upon HSV-1 infection, resulting in enhanced HSV-1 replication. ChIP-seq to identify TFIIIA transcriptional targets; patient fibroblasts and GTF3A gene-edited cell lines; innate immune response assays; viral replication assays Science immunology High 36399538
1990 In Xenopus, TFIIIA from somatic cells (S-TFIIIA) initiates transcription from a different promoter >200 bp upstream of the oocyte start site, producing a protein with 22 additional N-terminal amino acids. Both O-TFIIIA and S-TFIIIA bind the 5S RNA gene and 5S RNA equivalently, and both promote stable transcription complexes on oocyte-type 5S RNA genes. Transcription start site mapping; protein characterization; in vitro transcription in nuclear extract Genes & development Medium 2253880
1990 TFIIIA finds its binding site on 5S DNA via a DNA-mediated transfer mechanism (sliding/transfer between sites on the same DNA molecule), as demonstrated with immobilized agarose-linked plasmids. This transfer mechanism underpins TFIIIA-induced all-or-none DNA gyration and contributes to the differential activation of somatic vs. oocyte 5S RNA genes. TFIIIA-induced supercoiling assays with agarose-immobilized plasmids; competitive binding experiments Cell Low 3698098
1995 A TFIIIA binding site was identified in the 5' flanking region of the Xenopus TFIIIA gene itself (nucleotides -326 to -264), with lower affinity than the 5S gene ICR. When TFIIIA is bound to 5S RNA in 7S RNP, it does not bind this upstream element. This site overlaps with a negative regulatory element at -306 to -289 of the TFIIIA gene, suggesting TFIIIA may autorepress its own gene transcription. DNase I footprinting; EDTA inhibition; competition with 7S RNP Nucleic acids research Low 2349091

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 S. cerevisiae TFIIIB is the transcription initiation factor proper of RNA polymerase III, while TFIIIA and TFIIIC are assembly factors. Cell 445 2404611
1984 Xenopus 5S gene transcription factor, TFIIIA: characterization of a cDNA clone and measurement of RNA levels throughout development. Cell 281 6210149
1986 Sequence homology of the yeast regulatory protein ADR1 with Xenopus transcription factor TFIIIA. Nature 185 3515197
1988 Mapping functional regions of transcription factor TFIIIA. Molecular and cellular biology 159 2837652
1997 Solution structure of the first three zinc fingers of TFIIIA bound to the cognate DNA sequence: determinants of affinity and sequence specificity. Journal of molecular biology 158 9367756
1992 RNA and DNA binding zinc fingers in Xenopus TFIIIA. Cell 149 1423623
1988 Stability of RNA in developing Xenopus embryos and identification of a destabilizing sequence in TFIIIA messenger RNA. Development (Cambridge, England) 142 2458900
1997 Domain packing and dynamics in the DNA complex of the N-terminal zinc fingers of TFIIIA. Nature structural biology 118 9253405
1990 A finger protein structurally similar to TFIIIA that binds exclusively to 5S RNA in Xenopus. Cell 102 2331751
1992 Specific interaction of the first three zinc fingers of TFIIIA with the internal control region of the Xenopus 5 S RNA gene. Journal of molecular biology 99 1538401
1986 Structure of the gene for Xenopus transcription factor TFIIIA. Nucleic acids research 99 3754326
1993 A role in DNA binding for the linker sequences of the first three zinc fingers of TFIIIA. Nucleic acids research 94 8346014
1992 Structure of the TFIIIA-5 S DNA complex. Journal of molecular biology 84 1404361
1984 Altered levels of a 5 S gene-specific transcription factor (TFIIIA) during oogenesis and embryonic development of Xenopus laevis. The Journal of biological chemistry 84 6206067
1990 Mode of interaction of the zinc finger protein TFIIIA with a 5S RNA gene of Xenopus. Proceedings of the National Academy of Sciences of the United States of America 68 2164687
1987 Transient activation of oocyte 5S RNA genes in Xenopus embryos by raising the level of the trans-acting factor TFIIIA. Cell 67 3664642
1992 The deduced sequence of the transcription factor TFIIIA from Saccharomyces cerevisiae reveals extensive divergence from Xenopus TFIIIA. The Journal of biological chemistry 61 1737784
1991 RNA-protein interactions of stored 5S RNA with TFIIIA and ribosomal protein L5 during Xenopus oogenesis. Developmental biology 56 1995392
2004 Zn-, Cd-, and Pb-transcription factor IIIA: properties, DNA binding, and comparison with TFIIIA-finger 3 metal complexes. Journal of inorganic biochemistry 55 15134923
1986 TFIIIA and homologous genes. The 'finger' proteins. Nucleic acids research 54 3086841
1998 Differential nucleosome positioning on Xenopus oocyte and somatic 5 S RNA genes determines both TFIIIA and H1 binding: a mechanism for selective H1 repression. Journal of molecular biology 53 9737930
2007 Differential expression of the TFIIIA regulatory pathway in response to salt stress between Medicago truncatula genotypes. Plant physiology 41 17951460
1993 TFIIIA: nine fingers--three hands? Trends in biochemical sciences 40 7688487
1992 Differential binding of zinc fingers from Xenopus TFIIIA and p43 to 5S RNA and the 5S RNA gene. Molecular and cellular biology 40 1620123
1989 Electron microscopy reveals that transcription factor TFIIIA bends 5S DNA. Molecular and cellular biology 40 2927394
1987 Transcriptionally inactive oocyte-type 5S RNA genes of Xenopus laevis are complexed with TFIIIA in vitro. Molecular and cellular biology 40 3683391
1991 Involvement of "hinge" nucleotides of Xenopus laevis 5 S rRNA in the RNA structural organization and in the binding of transcription factor TFIIIA. Journal of molecular biology 38 2002508
1987 TFIIIA binds to different domains of 5S RNA and the Xenopus borealis 5S RNA gene. Molecular and cellular biology 38 3431548
1998 Nucleosome translational position, not histone acetylation, determines TFIIIA binding to nucleosomal Xenopus laevis 5S rRNA genes. Molecular and cellular biology 37 9488430
1988 The TFIIIA recognition fragment d(GGATGGGAG).d(CTCCCATCC) is B-form in solution. Nucleic acids research 37 3375064
1995 Differential binding of oocyte-type and somatic-type 5S rRNA to TFIIIA and ribosomal protein L5 in Xenopus oocytes: specialization for storage versus mobilization. Developmental biology 36 7729570
1988 TFIIIA binds with equal affinity to somatic and major oocyte 5S RNA genes. Genes & development 35 3360323
1998 The role of zinc finger linkers in p43 and TFIIIA binding to 5S rRNA and DNA. Nucleic acids research 34 9443960
1996 Transcription factor IIIA (TFIIIA) in the second decade. Journal of cell science 33 8907699
1986 The developmental expression of the gene for TFIIIA in Xenopus laevis. Nucleic acids research 33 3755818
2009 Alternative splicing of anciently exonized 5S rRNA regulates plant transcription factor TFIIIA. Genome research 32 19211543
1994 Contribution of individual base pairs to the interaction of TFIIIA with the Xenopus 5S RNA gene. Biochemistry 32 8011622
1987 The 5S gene internal control region is B-form both free in solution and in a complex with TFIIIA. Nature 32 3657961
1986 The role of DNA-mediated transfer of TFIIIA in the concerted gyration and differential activation of the Xenopus 5S RNA genes. Cell 31 3698098
2022 GTF3A mutations predispose to herpes simplex encephalitis by disrupting biogenesis of the host-derived RIG-I ligand RNA5SP141. Science immunology 30 36399538
1991 Detection of two Zn-finger proteins of Xenopus laevis, TFIIIA, and p43, by probing western blots of ovary cytosol with 65Zn2+, 63Ni2+, or 109Cd2+. Biological trace element research 29 1713475
1995 The only essential function of TFIIIA in yeast is the transcription of 5S rRNA genes. Proceedings of the National Academy of Sciences of the United States of America 28 7568129
1992 A new approach to the analysis of DNase I footprinting data and its application to the TFIIIA/5S DNA complex. Nucleic acids research 28 1408784
1997 Strand-specific modulation of UV photoproducts in 5S rDNA by TFIIIA binding and their effect on TFIIIA complex formation. Biochemistry 27 9354642
1998 Structural determinants in 5S RNA and TFIIIA for 7S RNP formation. European journal of biochemistry 25 9874245
1993 Role of TFIIIA zinc fingers in vivo: analysis of single-finger function in developing Xenopus embryos. Molecular and cellular biology 25 8336715
1993 A position-dependent transcription-activating domain in TFIIIA. Molecular and cellular biology 24 8246967
1992 Interaction of Xenopus TFIIIC with the TFIIIA.5 S RNA gene complex. The Journal of biological chemistry 24 1517247
1992 Characterization of a Xenopus oocyte factor that binds to a developmentally regulated cis-element in the TFIIIA gene. Developmental biology 24 1577195
1991 The carboxyterminal zinc fingers of TFIIIA interact with the tip of helix V of 5S RNA in the 7S ribonucleoprotein particle. Nucleic acids research 24 1827669
1991 The use of chemical nucleases to analyze RNA-protein interactions. The TFIIIA-5 S rRNA complex. The Journal of biological chemistry 24 1939152
1989 Two TFIIIA activities regulate expression of the Xenopus 5S RNA gene families. Genes & development 24 2575558
1987 Transition mutations within the Xenopus borealis somatic 5S RNA gene can have independent effects on transcription and TFIIIA binding. Molecular and cellular biology 23 3561399
2008 Dicistronic tRNA-5S rRNA genes in Yarrowia lipolytica: an alternative TFIIIA-independent way for expression of 5S rRNA genes. Nucleic acids research 22 18790808
1995 Cloning and expression analysis of a human cDNA homologous to Xenopus TFIIIA. Gene 22 7622052
1998 A hydrophobic segment within the 81-amino-acid domain of TFIIIA from Saccharomyces cerevisiae is essential for its transcription factor activity. Molecular and cellular biology 21 9418889
1993 Proteolytic footprinting of transcription factor TFIIIA reveals different tightly binding sites for 5S RNA and 5S DNA. Molecular and cellular biology 21 7689146
1990 The characterization of the TFIIIA synthesized in somatic cells of Xenopus laevis. Genes & development 21 2253880
1990 Additional intragenic promoter elements of the Xenopus 5S RNA genes upstream from the TFIIIA-binding site. Molecular and cellular biology 21 2398887
1997 Molecular biology of vertebrate transcription factor IIIA: cloning and characterization of TFIIIA from channel catfish oocytes. Gene 19 9426240
1995 Coordinate regulation of ribosomal component synthesis in Acanthamoeba castellanii: 5S RNA transcription is down regulated during encystment by alteration of TFIIIA activity. Molecular and cellular biology 19 7760828
1995 Molecular cloning, characterization, and chromosomal mapping of a novel human gene (GTF3A) that is highly homologous to Xenopus transcription factor IIIA. Cytogenetics and cell genetics 19 7789179
1993 Dissection of the DNA-binding domain of Xenopus laevis TFIIIA. Quantitative DNase I footprinting analysis of specific complexes between a 5 S RNA gene fragment and N-terminal fragments of TFIIIA containing three, four or five zinc-finger domains. Journal of molecular biology 19 8377197
1991 TFIIIA induced DNA bending: effect of low ionic strength electrophoresis buffer conditions. Nucleic acids research 19 2011525
1989 Crosslinking of transcription factor TFIIIA to ribosomal 5S RNA from X. laevis by trans-diamminedichloroplatinum (II). Nucleic acids research 19 2602112
1988 Upstream sequences required for transcription of the TFIIIA gene in Xenopus oocytes. Nucleic acids research 17 3375072
1991 Contacts between 5 S DNA and Xenopus TFIIIA identified using 5-azido-2'-deoxyuridine-substituted DNA. The Journal of biological chemistry 15 1885581
1995 Zinc(II) ions selectively interact with DNA sequences present at the TFIIIA binding site of the Xenopus 5S-RNA gene. Nucleic acids research 14 7630723
1991 Regulation of the Xenopus laevis transcription factor IIIA gene during oogenesis and early embryogenesis: negative elements repress the O-TFIIIA promoter in embryonic cells. Developmental biology 14 2040372
1989 Presence of multiple species of polypeptides immunologically related to transcription factor TFIIIA in adult Xenopus tissues. Nucleic acids research 14 2762150
2010 A conserved alternative splicing event in plants reveals an ancient exonization of 5S rRNA that regulates TFIIIA. RNA biology 12 20699638
2000 Energetics of the specific binding interaction of the first three zinc fingers of the transcription factor TFIIIA with its cognate DNA sequence. Proteins 12 11013400
2007 Zinc fingers 1 and 7 of yeast TFIIIA are essential for assembly of a functional transcription complex on the 5 S RNA gene. Nucleic acids research 11 17626045
1995 Human TFIIIA alone is sufficient to prevent nucleosomal repression of a homologous 5S gene. Nucleic acids research 11 7870575
1992 Binding of TFIIIA to derivatives of 5S RNA containing sequence substitutions or deletions defines a minimal TFIIIA binding site. Nucleic acids research 11 1614850
2005 Mutations in TFIIIA that increase stability of the TFIIIA-5 S rRNA gene complex: unusual effects on the kinetics of complex assembly and dissociation. The Journal of biological chemistry 10 15888446
2003 The Xenopus B2 factor involved in TFIIIA gene regulation is closely related to Sp1 and interacts in a complex with USF. Gene 10 12609741
1988 Characterization by human antibodies of two HeLa cell proteins which are related to Xenopus laevis transcription factor TFIIIA. Nucleic acids research 10 3362672
2004 Signals and receptors for the nuclear transport of TFIIIA in Xenopus oocytes. European journal of cell biology 9 15146977
1998 Xenopus TFIIIA gene transcription is dependent on cis-element positioning and chromatin structure. Molecular and cellular biology 9 9632765
1987 Novobiocin interferes with the binding of transcription factors TFIIIA and TFIIIC to the promoters of class III genes. Nucleic acids research 9 3588299
2003 Isolation of the B3 transcription factor of the Xenopus TFIIIA gene. Gene 8 12957389
1993 Transcription factor IIIA (TFIIIA): an update. Experientia 8 8224095
2013 Localized frustration and binding-induced conformational change in recognition of 5S RNA by TFIIIA zinc finger. The journal of physical chemistry. B 7 24266699
1990 Identification of a TFIIIA binding site on the 5' flanking region of the TFIIIA gene. Nucleic acids research 7 2349091
2011 Role of Linkers between Zinc Fingers in Spacing Recognition by Plant TFIIIA-Type Zinc-Finger Proteins. Journal of amino acids 6 22312478
2004 Restricted specificity of Xenopus TFIIIA for transcription of somatic 5S rRNA genes. Molecular and cellular biology 6 14993284
1994 Overlapping transcription by RNA polymerases II and III of the Xenopus TFIIIA gene in somatic cells. The Journal of biological chemistry 6 7929274
1990 Reaction parameters of TFIIIA-induced supercoiling catalyzed by a Xenopus laevis cell-free extract. Nucleic acids research 6 2315014
1995 The interaction of TFIIIA with specific RNA-DNA heteroduplexes. The Journal of biological chemistry 5 7559384
1995 Silkworm TFIIIA requires additional class III factors for commitment to transcription complex assembly on a 5S RNA gene. Nucleic acids research 5 7739903
1991 Yeast TFIIIA + TFIIIC/tau-factor, but not yeast TFIIIA alone, interacts with the Xenopus 5S rRNA gene. Nucleic acids research 5 2011529
2022 Molecular Dynamics Simulations of Reduced and Oxidized TFIIIA Zinc Fingers Free and Interacting with 5S RNA. Journal of chemical information and modeling 4 35143196
2020 Duplication and subfunctionalisation of the general transcription factor IIIA (gtf3a) gene in teleost genomes, with ovarian specific transcription of gtf3ab. PloS one 4 31999691
2003 Influence of TFIIIA-type linker at the N- or C-terminal of nine-zinc finger protein on DNA-binding site. Biochemical and biophysical research communications 4 12480525
1986 5S RNA gene specific transcription factor (TFIIIA) changes the linking number of the DNA. Biochemical and biophysical research communications 4 3004481
1991 Xenopus transcription factor IIIC (TFIIIC) specifically interacts with the "B" block region of the TFIIIA gene. Biochemical and biophysical research communications 3 2025235
2023 "Pathomorphogenic" Changes Caused by Citrus Bark Cracking Viroid and Transcription Factor TFIIIA-7ZF Variants Support Viroid Propagation in Tobacco. International journal of molecular sciences 2 37175498
1989 Expression of functional Xenopus TFIIIA in Escherichia coli. Nucleic acids research 2 2648333
1990 Transcription factor TFIIIA stimulates DNA supercoiling promoted by a fractionated cell-free extract from Xenopus laevis. European journal of biochemistry 1 2209588

Missed literature

Know a paper Affinage missed for GTF3A? Flag it for the maintainers and the community.

No submissions yet.