Affinage

PURA

Transcriptional activator protein Pur-alpha · UniProt Q00577

Length
322 aa
Mass
34.9 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PURA (Pur-alpha) is a sequence-specific single-stranded DNA/RNA-binding protein that functions both as a context-dependent transcriptional regulator and as a component of cytoplasmic ribonucleoprotein transport machinery, with essential roles in neuronal development (PMID:12972605, PMID:19846792). Its central nucleic-acid-binding core is built from tandem 'PUR repeats' adopting a Whirly-like fold that dimerizes and engages DNA or RNA through concave beta-sheet surfaces, recognizing target bases in a sequence-specific manner (PMID:19846792, PMID:26744780). Through this core PURA exhibits ATP-independent helix-destabilizing (unwindase) activity, contacting the purine-rich strand of duplex DNA while displacing the pyrimidine-rich strand, an activity dependent on conserved arginine, aromatic, and a critical phenylalanine residue (PMID:11169743, PMID:15777841, PMID:26744780). PURA acts as a transcriptional activator or repressor depending on its promoter context and protein partners: it represses E2F-1-driven transcription (PMID:10597240) and the androgen receptor gene via an hnRNP-K repressor complex (PMID:18413735), represses the IL-9 promoter in T cells (PMID:37909329), and activates JCV promoters together with YB-1 (PMID:10082537) and Snail2 to drive EMT (PMID:33144099). PURA restrains cell-cycle progression—its levels and Rb association are cell-cycle regulated, it co-occupies promoters with and stimulates cyclin A/Cdk2, and microinjected PURA arrests cells at mitosis (PMID:9716182, PMID:10435638, PMID:15707957). In neurons, PURA assembles into RNA-dependent mRNP complexes with Staufen, FMRP, and myosin Va, and links BC1/BC200 RNA to microtubules to drive dendritic mRNA transport (PMID:12147688, PMID:16511857, PMID:11032866). Subcellular partitioning of PURA is tightly controlled: dephosphorylation by DUSP8 upon TGF-beta signaling triggers nuclear export and de-repression of target promoters (PMID:37909329), and binding RNAs (including 7SL- and 18S rRNA-homologous species) modulate its self-association, DNA binding, and translational activity (PMID:9712838, PMID:10412036, PMID:11596104). Loss of PURA in mice causes postnatal neurodegeneration, seizures, and death with defective neuronal proliferation and myelination (PMID:12972605), while disease-causing point mutations underlie a 5q31.3 deletion/mutation syndrome explained structurally (PMID:26744780); in FXTAS and ALS, PURA is sequestered into pathological rCGG-repeat inclusions and FUS-positive stress granules (PMID:17698009, PMID:26728149).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1995 High

    Established that PURA physically engages the cell-cycle master regulator Rb in a manner reciprocally antagonized by its ssDNA recognition element, linking PURA's nucleic-acid-binding function to cell-cycle control.

    Evidence GST pull-down, co-IP, and deletion mutagenesis with purified proteins

    PMID:7592647

    Open questions at the time
    • Did not establish the in vivo consequence of disrupting the PURA-Rb complex
    • Rb-binding domain mapped only by homology to SV40 large T-antigen
  2. 1996 High

    Showed PURA is co-opted by viral transcription/replication machinery, binding HIV-1 Tat and JCV T-antigen and modulating viral promoter activity and DNA replication, revealing its role as a sequence-specific regulator at viral origins.

    Evidence Co-IP, GST binding assays, DNA footprinting/band-shift, and replication/reporter assays in glial cells

    PMID:8648759 PMID:8943069

    Open questions at the time
    • Did not resolve whether viral interactions reflect a cellular function co-opted by the virus
    • Mechanism of T-antigen stimulation of PURA ori binding not defined
  3. 1998 High

    Extended PURA's nucleic-acid binding to RNA (HIV-1 TAR) and revealed that a co-purifying 7SL-homologous RNA negatively regulates its DNA binding, introducing RNA as a co-regulator of PURA activity.

    Evidence Gel-shift with purified proteins, deletion mapping, reporter assays, and RNA co-immunopurification

    PMID:9524214 PMID:9712838

    Open questions at the time
    • In vivo significance of the regulatory PU-RNA not established
    • Identity and biogenesis of the endogenous regulatory RNAs not fully defined
  4. 1999 High

    Defined PURA as a hub that contacts multiple transcriptional regulators (YB-1, E2F-1, cyclin A) and self-associates in an RNA-dependent manner, positioning it to integrate cell-cycle and transcription signals.

    Evidence GST pull-down, reciprocal affinity chromatography/co-IP, gel-shift, RNase controls, and reporter assays; cell synchronization with immunoEM

    PMID:10082537 PMID:10412036 PMID:10500218 PMID:10597240 PMID:9716182

    Open questions at the time
    • How RNA-dependent self-association is regulated in cells not resolved
    • Whether E2F-1 repression operates at endogenous target genes not tested here
  5. 1999 High

    Demonstrated a direct causal role for PURA in cell-cycle arrest, showing microinjected PURA blocks mitotic transit, elevating it from a binding partner of cell-cycle regulators to a functional restraint on proliferation.

    Evidence Microinjection of purified protein with time-lapse imaging and single-cell DNA photometry in NIH3T3

    PMID:10435638

    Open questions at the time
    • Molecular pathway connecting PURA to mitotic block not defined
    • Physiological levels versus injected excess not addressed
  6. 2000 Medium

    Identified PURA as a dendritic mRNA-transport factor, linking BC1 RNA to microtubules and participating in Pol III transcription of the BC1 gene, establishing its cytoplasmic RNA-transport function.

    Evidence In vitro RNA-binding, microtubule co-sedimentation, competition assays, and in vitro transcription with PURA depletion

    PMID:11032728 PMID:11032866

    Open questions at the time
    • In vivo transport dynamics not directly visualized
    • Cargo mRNA repertoire not defined
  7. 2001 High

    Resolved the biochemical basis of PURA's ATP-independent helix-destabilizing activity, mapping it to the central DNA-binding region and correlating it with sequence-specific binding, and showed PURA inhibits translation via 18S rRNA-homologous RNAs.

    Evidence In vitro oligonucleotide-displacement and translation assays with purified protein, deletion mutagenesis, RNA immunopurification

    PMID:11169743 PMID:11329617 PMID:11596104 PMID:11730934

    Open questions at the time
    • Physiological substrate of unwinding activity not identified
    • Translational inhibition demonstrated only in vitro
  8. 2002 Medium

    Placed PURA within neuronal mRNP transport granules containing Staufen, FMRP, and myosin Va in an RNA-dependent assembly associated with rough ER and a kinesin motor, defining its molecular context for dendritic transport.

    Evidence Polyribosome dissociation, co-IP with RNase controls, double-RNA IP

    PMID:12147688

    Open questions at the time
    • Direct versus RNA-bridged contacts within the mRNP not dissected
    • Functional consequence for translation at dendrites not measured
  9. 2003 High

    Established PURA's essential in vivo role in nervous-system development, showing knockout mice die postnatally with neuronal proliferation, lamination, and myelination defects and loss of Cdk5 from Purkinje dendrites.

    Evidence Targeted gene knockout with histological markers and co-IP from brain lysates

    PMID:12972605

    Open questions at the time
    • Which molecular activity (transcription, transport, unwinding) underlies the phenotype not isolated
    • Cell-autonomy of the defects not resolved
  10. 2005 High

    Refined PURA's cell-cycle role mechanistically, showing it binds and stimulates cyclin A/Cdk2 kinase activity and co-occupies the c-MYC promoter with Cdk2, connecting its transcriptional and kinase-regulatory functions.

    Evidence GST pull-down with CDKs, in vitro kinase assay, double ChIP in HeLa cells

    PMID:15707957

    Open questions at the time
    • Net effect on c-MYC expression not quantified
    • Specificity of CDK stimulation in vivo not tested
  11. 2005 High

    Detailed the strand-specific unwinding mechanism, showing PURA holds the purine-rich strand while displacing the pyrimidine-rich strand and requires arginine/aromatic and C-terminal residues, advancing the structural logic of its DNA action.

    Evidence Strand-displacement, permanganate probing, gp32 accessibility, and mutational analysis

    PMID:15777841

    Open questions at the time
    • Genomic loci unwound in cells not mapped
    • Coupling of unwinding to transcriptional output not established
  12. 2007 High

    Linked PURA to repeat-expansion neurodegeneration, showing it binds rCGG repeats, is sequestered in FXTAS patient inclusions, and dose-dependently rescues rCGG toxicity in Drosophila, defining a sequestration-based disease mechanism.

    Evidence RNA-binding assay, Drosophila genetic rescue, and patient brain immunohistochemistry

    PMID:17698009

    Open questions at the time
    • Which normal PURA function is lost upon sequestration not pinpointed
    • Quantitative depletion of soluble PURA in patients not measured
  13. 2008 High

    Defined a PURA-hnRNP-K repressor complex at the androgen receptor gene whose loss drives AR overexpression in prostate cancer, exemplifying PURA's transcriptional-repressor role and its epigenetic regulation.

    Evidence ChIP, co-IP, siRNA/overexpression, and pharmacological HDAC/methylation inhibitor treatment

    PMID:18413735

    Open questions at the time
    • Mechanism causing PURA nuclear exclusion in cancer not fully defined
    • Direct repressive mechanism at chromatin not dissected
  14. 2009 High

    Provided the first atomic-resolution view of the PUR domain, defining the Whirly-like fold, tandem PUR repeats, repeat-III-mediated dimerization, and dual beta-sheet nucleic-acid-binding surfaces.

    Evidence X-ray crystallography of Drosophila PURA, SAXS, SEC, and DNA/RNA binding with mutagenesis

    PMID:19846792

    Open questions at the time
    • Structure lacked bound nucleic acid
    • Full-length and human protein architecture not resolved
  15. 2012 Medium

    Showed that RNA binding and dimerization are jointly required for nuclear export and cytoplasmic transport of PURA-mRNP complexes, mechanistically coupling the structural features to its transport function.

    Evidence GFP-fusion localization in Drosophila oogenesis, co-purification MS, RNA-binding and mutant analysis

    PMID:22614836

    Open questions at the time
    • Mammalian relevance of the oogenesis transport pathway not established
    • Export receptor not identified
  16. 2016 High

    Resolved how PURA recognizes ssDNA and unwinds duplex, identifying an essential phenylalanine required for both unwinding and neuroprotection, and explained the structural basis of 5q31.3-syndrome point mutations.

    Evidence Co-crystal structure with ssDNA, NMR, in vitro unwinding assay, mutagenesis, and Drosophila in vivo assay

    PMID:26744780

    Open questions at the time
    • In vivo unwinding substrates in mammalian neurons not identified
    • Genotype-phenotype map across patient mutations incomplete
  17. 2016 High

    Connected PURA to ALS pathology, showing it interacts with FUS, is recruited to stress granules, is required for SG formation, and suppresses mutant FUS mislocalization and toxicity, defining a stress-granule regulatory role.

    Evidence Co-IP, immunofluorescence co-localization, shRNA knockdown with SG quantification, and overexpression toxicity rescue in motor neurons

    PMID:26728149

    Open questions at the time
    • Whether PURA acts as a scaffold or signaling component of SGs not resolved
    • Direct versus indirect FUS contact not mapped at residue level
  18. 2023 High

    Identified DUSP8-mediated dephosphorylation as a signal-controlled switch driving PURA nuclear export and de-repression of the IL-9 promoter, providing a post-translational mechanism governing PURA's repressor activity in T cells.

    Evidence T cell conditional knockout, mass spectrometry, ChIP-Seq, co-IP, phosphorylation and reporter assays, and an allergic asthma model

    PMID:37909329

    Open questions at the time
    • Kinase counteracting DUSP8 not identified
    • Generalizability of the phospho-switch to other PURA target genes not tested
  19. 2023 Medium

    Expanded PURA's oncogenic interactome by identifying the MEST-PURA interaction driving ERK-Snail metastatic signaling and a small molecule blocking it, while circRNA-mediated cytoplasmic retention regulating promoter recruitment links RNA control to disease.

    Evidence CRISPR screen, co-IP/MS, SPR, invasion/metastasis assays; RNA pull-down/RIP/ChIP in AD models

    PMID:33144099 PMID:34504314 PMID:37149929

    Open questions at the time
    • Whether MEST-PURA signaling depends on PURA nucleic-acid binding not resolved
    • Direct versus indirect effects on the named target genes not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PURA's distinct molecular activities—sequence-specific transcription, ATP-independent unwinding, and RNA transport—are partitioned and prioritized in vivo, and which activity is decisive for its neurodevelopmental essentiality, remains unresolved.
  • No separation-of-function in vivo dissection linking specific activities to the knockout phenotype
  • Genome-wide endogenous DNA/RNA target maps incomplete
  • Physiological unwinding substrates unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0140097 catalytic activity, acting on DNA 3 GO:0045182 translation regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0000228 nuclear chromosome 2 GO:0005856 cytoskeleton 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 3
Partners
CDK2DUSP8E2F1FUSHNRNPKMESTRB1YB-1
Complex memberships
PURA-hnRNP-K repressor complexcytoplasmic stress granuledendritic transport mRNP (with Staufen/FMRP/myosin Va)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Pur-alpha binds the hypophosphorylated form of Rb (retinoblastoma protein) with high affinity via a domain with limited homology to the SV40 large T-antigen Rb-binding region; the single-stranded DNA Pur-alpha recognition element disrupts the Pur-alpha–Rb complex, and conversely high concentrations of Rb prevent Pur-alpha from binding DNA. GST pull-down with purified proteins, co-immunoprecipitation from cell lysates, deletion mutagenesis The Journal of biological chemistry High 7592647
1996 HIV-1 Tat protein interacts with Pur-alpha through two leucine-rich repeats in Pur-alpha; Tat enhances Pur-alpha binding to the JCV upTAR element and together they synergistically activate transcription from an upTAR-containing promoter in a cell-cycle-dependent manner. Co-immunoprecipitation from cell extracts, GST-Pur-alpha binding assay, transcription reporter (cotransfection) Proceedings of the National Academy of Sciences of the United States of America High 8943069
1996 Overexpression of Pur-alpha suppresses replication of JCV DNA in glial cells; Pur-alpha and JCV T-antigen share a common binding region in the single-stranded JCV ori sequence, and T-antigen stimulates Pur-alpha association with the ori; co-immunoprecipitation revealed a molecular association between Pur-alpha and JCV T-antigen in cells. JCV DNA replication assay in transfected cells, DNA footprinting, band-shift assay, co-immunoprecipitation/Western blot Journal of virology High 8648759
1998 Pur-alpha binds HIV-1 TAR RNA in a sequence-specific manner; amino acids 55–85 (first basic aromatic repeat) are important for TAR RNA binding; overexpression of Pur-alpha increases transcription of the HIV-1 LTR through a TAR-dependent mechanism. Competition gel-shift analysis with purified proteins, deletion-mutant mapping, reporter gene assay in glial cells Gene High 9524214
1998 Pur-alpha physically and functionally interacts with JCV large T-antigen; the interaction attenuates T-antigen-mediated transcriptional activation; deletion mutants of Pur-alpha unable to bind T-antigen cannot suppress T-antigen transactivation. Co-immunoprecipitation, GST affinity binding assay, deletion mutagenesis, transient transfection reporter assay The Journal of biological chemistry High 9830007
1998 A cellular RNA homologous to 7SL RNA co-purifies with Pur-alpha; this PU-RNA inhibits Pur-alpha binding to the MBP promoter MB1 DNA sequence, suggesting RNA acts as a negative co-regulator of Pur-alpha DNA-binding activity. Co-immunopurification of RNA with Pur-alpha, band-shift competition assay, Northwestern analysis with deletion mutants The Journal of biological chemistry Medium 9712838
1999 The HIV-1 Tat–Pur-alpha interaction is mediated by RNA; a 10-nt GC-rich consensus RNA associated with Pur-alpha is required for the Pur-alpha:Tat interaction in an in vitro reconstitution assay; expression of this RNA in cells enhances HIV-1 promoter activation by Tat and Pur-alpha. In vitro reconstitution assay with purified proteins and RNA, reporter gene assay in cells Proceedings of the National Academy of Sciences of the United States of America High 10500218
1999 Pur-alpha directly associates with YB-1 protein in the absence of DNA (shown by affinity chromatography and co-immunoprecipitation); residues 85–215 of Pur-alpha and 75–203 of YB-1 mediate the interaction; Pur-alpha and YB-1 together synergistically activate JCV promoter activity via the 23-bp LCE element. Affinity chromatography, co-immunoprecipitation, band-shift assay, deletion mutagenesis, cotransfection reporter assay Molecular and cellular biology High 10082537
1999 Pur-alpha associates with E2F-1 in the absence of DNA (GST pull-down and co-IP from nuclear extracts); this association inhibits E2F-1 binding to its target DNA and suppresses E2F-1-mediated transcriptional activation of the DHFR promoter; co-expression of Pur-alpha with E2F-1 increases E2F-1 protein stability. GST pull-down, combined immunoprecipitation/Western blot from nuclear extracts, band-shift assay, reporter gene cotransfection Oncogene High 10597240
1999 Pur-alpha self-associates in an RNA-dependent manner; the self-association domain maps to acidic leucine-rich repeats (the same region that interacts with HIV-1 Tat); Tat disrupts Pur-alpha self-association; RNA both mediates self-association and inhibits Pur-alpha binding to its target DNA sequence. GST pull-down with bacterially expressed proteins, synthetic peptides, electrophoretic mobility-shift assay with/without RNase treatment Journal of cellular biochemistry Medium 10412036
1999 Pur-alpha cell-cycle levels decline just before S-phase onset and peak after mitosis; Pur-alpha–Rb complexes dissipate as cells enter S phase; in S/G2, Pur-alpha localizes to nuclear foci containing newly replicated DNA and co-immunoprecipitates with cyclin A from S and G2 phase extracts. Cell synchronization, co-immunoprecipitation, immunoelectron microscopy with BrdU labeling, confocal microscopy Cell growth & differentiation High 9716182
1999 Microinjection of purified Pur-alpha into NIH3T3 cells arrests ~80% of cells from passing through mitosis; cells injected in S or G2 are blocked with 4N DNA content; cells injected in G1 either die or arrest at 2N or 4N. Microinjection, video time-lapse microscopy, quantitative DNA photometry of individual cells Oncogene High 10435638
2000 Pur-alpha and Pur-beta link BC1 RNA to microtubules by binding the 5'-proximal dendrite-targeting motifs (G/U-rich) of BC1 RNA; this interaction is mutually exclusive with Translin binding to the same motifs. In vitro RNA-binding assays with purified proteins, microtubule co-sedimentation, competition binding assays Journal of neurochemistry Medium 11032866
2000 Pur-alpha interacts with Tat in nuclear chromatin of human glial cells; Pur-alpha and Tat are co-localized in extranucleolar chromatin; the Tat–Pur-alpha interaction is direct (not through an RNA bridge) but is strongly enhanced by RNA; Tat residues 49–72 (TAR RNA-binding domain) are critical for binding Pur-alpha, while Pur-alpha repeat II domains mediate the interaction. Immunoelectron microscopy, in vitro binding of purified proteins ± RNase, peptide inhibition, domain deletion mapping Journal of cellular biochemistry High 10679817
2001 Pur-alpha has ATP-independent helix-destabilizing activity, displacing an oligonucleotide annealed to ssDNA in a dose-, time-, and temperature-dependent manner; the activity maps to the central DNA-binding region (aa 72–274) and correlates with sequence-specific DNA binding. In vitro helix-unwinding assay (oligonucleotide displacement from M13 DNA), deletion mutagenesis, heat-inactivation controls Journal of cellular biochemistry High 11169743
2001 HIV-1 Tat, together with Pur-alpha, activates JCV DNA replication initiated at the JCV origin; in an in vitro replication system, Tat with Pur-alpha achieved >6-fold activation over T-antigen alone; Cys22 of Tat exerts a conformational effect critical for both replication activation and Pur-alpha binding. In vitro DNA replication assay, transfection-based replication assay in glial cells, mutant Tat analysis The Journal of general virology High 11413364
2001 Pur-alpha inhibits translation in vitro in a dose-dependent manner, likely through its association with 18S rRNA-homologous RNAs; this inhibition is abrogated by HIV-1 Tat protein. In vitro coupled transcription/translation assay with GST-Pur-alpha, luciferase reporter; RNA immunopurification and sequencing of PARNA species Journal of cellular biochemistry Medium 11596104
2001 Pur-alpha protein levels and nuclear localization are cell-cycle regulated; nuclear vs. cytoplasmic localization is controlled by protein modification and specific sequence domains, including a PEST sequence (aa 215–231) and destruction motifs; in the nucleus Pur-alpha colocalizes with CDK2 and cyclin A, while at mitosis it colocalizes with cyclin B1 in the cytoplasm. Stable transfection with Pur-alpha constructs, subcellular fractionation, confocal microscopy, deletion mutant analysis Journal of cellular biochemistry Medium 11329617
2001 Pur-alpha interacts with cyclin T1 and Cdk9 through distinct adjacent domains; together with Tat, this complex activates TNF-alpha promoter (a TAR-negative promoter) with Pur-alpha acting as a bridge assembling Tat, cyclin T1, and Cdk9. Protein-protein binding studies (domain mapping), cotransfection reporter assay in astrocytic cells Journal of neuroimmunology Medium 11730934
2002 Pur-alpha is found in mRNP complexes together with mStaufen, FMRP, and myosin Va; the co-immunoprecipitation of these proteins by anti-Pur-alpha antibody is abolished by RNase treatment, indicating RNA-dependent mRNP assembly; these mRNPs reside on rough ER equipped with a kinesin motor. EDTA-dissociation of polyribosomes, co-immunoprecipitation with/without RNase, double-RNA immunoprecipitation The Journal of biological chemistry Medium 12147688
2003 Genetic inactivation of PURA in mice causes severe neurological defects (tremor, seizures) and death by 4 weeks; PURA-/- mice show reduced neuronal proliferation in hippocampus/cerebellum, aberrant lamination, reduced myelination, and absence of Cdk5 from Purkinje cell dendrites; Pur-alpha and Cdk5 co-immunoprecipitate from brain lysates of wild-type mice. Gene knockout (targeted disruption), immunohistochemistry (MCM7, GFAP, neurofilament markers), co-immunoprecipitation from brain lysates Molecular and cellular biology High 12972605
2005 Pur-alpha specifically interacts with Cdk2 (and Cdk1) but not Cdk6 in pull-down assays; Pur-alpha stimulates histone H1 phosphorylation by cyclin A/Cdk2 several-fold in vitro; double chromatin immunoprecipitation shows Pur-alpha and Cdk2 co-occupy DNA segments upstream of c-MYC in HeLa cells. GST pull-down with purified CDKs, in vitro kinase assay with baculovirus-produced cyclin A/Cdk2, double ChIP Biochemical and biophysical research communications High 15707957
2005 Pur-alpha unwinds duplex DNA by maintaining contact with the purine-rich strand and displacing the pyrimidine-rich strand; arginine and aromatic residues in the repeat region are essential for both ssDNA and duplex DNA binding; C-terminal sequences of Pur-alpha are required for binding linearized (but not supercoiled) DNA, and Pur-alpha binding generates regularly-spaced bands on agarose gels consistent with localized unwinding quanta. In vitro strand-displacement assay, mutational analysis, potassium permanganate probing for single-stranded regions, phage T4 gp32 accessibility assay Biochimica et biophysica acta High 15777841
2006 Pur-alpha binds BC200 RNA (human) and BC1 RNA (mouse), both implicated in dendritic targeting; Pur-alpha is specifically localized in dendrites (co-localizing with MAP2) but not axons; microtubule disruptors inhibit Pur-alpha dendritic targeting and cause its mislocalization to axons; double-RNA immunoprecipitation places Pur-alpha together with Staufen or FMRP on BC1 RNA and specific dendritic mRNAs in vivo. Immunofluorescence in hippocampal neurons in situ, RNA co-immunoprecipitation from mouse brain (double-RNA IP), microtubule disruption experiments Journal of neuroscience research High 16511857
2007 Pur-alpha binds rCGG repeats in a sequence-specific manner conserved between mammals and Drosophila; overexpression of Pur-alpha in Drosophila suppresses rCGG-repeat-mediated neurodegeneration in a dose-dependent manner; Pur-alpha is present in intranuclear inclusions of FXTAS patient brains, indicating it is sequestered by expanded rCGG repeats. RNA-binding assay (sequence-specific rCGG interaction), Drosophila genetic overexpression with neurodegeneration readout, immunohistochemistry of patient brain inclusions Neuron High 17698009
2008 Pur-alpha and hnRNP-K form a repressor complex that binds a specific sequence in the androgen receptor (AR) gene 5'-UTR; loss of Pur-alpha nuclear localization and AR promoter binding (by ChIP) correlates with AR overexpression in androgen-independent prostate cancer; restoring Pur-alpha expression reduces AR mRNA and protein levels; HDAC and DNA methylation inhibitors restore Pur-alpha nuclear localization and repressor complex binding. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation, siRNA knockdown, plasmid overexpression, pharmacological inhibitor treatment Cancer research High 18413735
2009 X-ray crystal structure of Drosophila Pur-alpha residues 40–185 reveals a 'Whirly-like' fold comprising two nearly identical structural motifs ('PUR repeats') that form a PUR domain; PUR domains are functional nucleic-acid binding domains; PUR repeat III mediates dimerization and the dimer adopts a Z-shaped arrangement as shown by SAXS; structural analysis and mutagenesis suggest nucleic acids are bound through two independent concave beta-sheet surface regions. X-ray crystallography, small-angle X-ray scattering (SAXS), size-exclusion chromatography, DNA/RNA binding assays, mutational studies Proceedings of the National Academy of Sciences of the United States of America High 19846792
2016 Crystal structure of the DNA/RNA-binding domain of Pur-alpha in complex with ssDNA reveals base-specific recognition; structure-based in vitro experiments resolved the unwindase mechanism showing a conserved phenylalanine is essential for unwinding activity; Drosophila in vivo analysis confirmed the phenylalanine is required for neuroprotective function; the structure explains how disease-causing point mutations in 5q31.3 syndrome impair function. X-ray crystallography (co-crystal with ssDNA), NMR, in vitro biochemical unwinding assay, site-directed mutagenesis, Drosophila in vivo functional assay eLife High 26744780
2016 Pur-alpha is a component of cytoplasmic stress granules (SGs) in ALS patient cells with FUS mutations; Pur-alpha physically interacts with FUS in mammalian neuronal cells; shRNA-mediated knockdown of Pur-alpha significantly reduces SG formation; ectopic Pur-alpha blocks cytoplasmic mislocalization of mutant FUS and suppresses mutant FUS toxicity in primary motor neurons. Co-immunoprecipitation, immunofluorescence co-localization, shRNA knockdown with SG quantification, overexpression in primary motor neurons with toxicity readout Acta neuropathologica High 26728149
2021 CircCwc27 directly binds Pur-alpha and increases cytoplasmic retention of Pur-alpha, suppressing Pur-alpha recruitment to promoters of AD-related genes (APP, Drd1, Ppp1r1b, Ntrk1, Lhx8); Pur-alpha overexpression phenocopies circCwc27 knockdown in preventing Aβ deposition. RNA pull-down, RIP (RNA immunoprecipitation), ChIP, knockdown/overexpression in AD mouse models Cell death and differentiation Medium 34504314
2023 DUSP8 phosphatase interacts with Pur-alpha and dephosphorylates Pur-alpha upon TGF-β signaling; dephosphorylation causes nuclear export of Pur-alpha, relieving Pur-alpha-mediated repression of the IL-9 promoter and promoting Th9 differentiation and allergic inflammation; Pur-alpha-deficient T cells show elevated Il-9 mRNA, confirming Pur-alpha acts as a transcriptional repressor of IL-9. T cell-specific conditional knockout mice, mass spectrometry, ChIP-Seq, co-immunoprecipitation, phosphorylation assay, reporter assay, mouse allergic asthma model The Journal of clinical investigation High 37909329
2000 Pur-alpha binds to BC1 RNA and is involved in the transcription of the BC1 RNA gene (Pol III); point mutations in the two putative Pur-alpha binding sites in the BC1 RNA gene reduce transcriptional activity in vitro; depletion of Pur-alpha from nuclear extracts inhibits BC1 RNA transcription. Co-immunoprecipitation of newly synthesized BC1 RNA, in vitro transcription assay, Pur-alpha depletion from nuclear extracts, site-directed mutagenesis of Pur-alpha binding sites Biochemical and biophysical research communications Medium 11032728
2012 Drosophila Pur-alpha accumulates in the oocyte early in oogenesis and is part of transported mRNP complexes; RNA binding (including to r(CGG)4 and r(CAG)4 trinucleotide repeats) and dimerization are both required for efficient nuclear export of Pur-alpha-mRNP complexes and translocation into the oocyte. GFP-fusion protein localization in Drosophila oogenesis, co-purification mass spectrometry, in vitro RNA-binding assay, mutant analysis (nucleic-acid binding and dimerization mutants) RNA biology Medium 22614836
2020 Pur-alpha enhances transcription of Snail2 by binding to its promoter region, thereby inducing EMT in esophageal squamous cell carcinoma; knockdown of Snail2 reverses Pur-alpha-induced EMT and suppresses migration/invasion. ChIP (chromatin immunoprecipitation), reporter assay, siRNA knockdown, RNA-seq, gain- and loss-of-function cell assays Cancer letters Medium 33144099
2023 MEST interacts with PURA; this MEST-PURA interaction activates SRCIN1/RASAL1-ERK-Snail signaling to promote cancer metastasis; blockade of the MEST-PURA interaction with small molecule G699-0288 inhibits cancer metastasis. CRISPR/Cas9 genome-wide screen, protein interactome (co-IP/MS), surface plasmon resonance, homology modeling, modified ELISA, functional invasion/metastasis assays EBioMedicine Medium 37149929

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of fragile X tremor/ataxia syndrome. Neuron 266 17698009
2002 Identification of mRNA/protein (mRNP) complexes containing Puralpha, mStaufen, fragile X protein, and myosin Va and their association with rough endoplasmic reticulum equipped with a kinesin motor. The Journal of biological chemistry 188 12147688
2003 Puralpha is essential for postnatal brain development and developmentally coupled cellular proliferation as revealed by genetic inactivation in the mouse. Molecular and cellular biology 152 12972605
2000 Puralpha: a multifunctional single-stranded DNA- and RNA-binding protein. Nucleic acids research 118 10954586
2000 Regulation of the human fas promoter by YB-1, Puralpha and AP-1 transcription factors. Gene 113 10903433
1995 Association of human Pur alpha with the retinoblastoma protein, Rb, regulates binding to the single-stranded DNA Pur alpha recognition element. The Journal of biological chemistry 107 7592647
1992 Pur-1, a zinc-finger protein that binds to purine-rich sequences, transactivates an insulin promoter in heterologous cells. Proceedings of the National Academy of Sciences of the United States of America 107 1454839
2006 Role of Pur alpha in targeting mRNA to sites of translation in hippocampal neuronal dendrites. Journal of neuroscience research 105 16511857
1996 Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Pur alpha. Proceedings of the National Academy of Sciences of the United States of America 91 8943069
2021 Circular RNA Cwc27 contributes to Alzheimer's disease pathogenesis by repressing Pur-α activity. Cell death and differentiation 90 34504314
1995 Cooperative action of cellular proteins YB-1 and Pur alpha with the tumor antigen of the human JC polyomavirus determines their interaction with the viral lytic control element. Proceedings of the National Academy of Sciences of the United States of America 88 7862639
2014 Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome. American journal of human genetics 84 25439098
2009 Multiple roles for Puralpha in cellular and viral regulation. Cell cycle (Georgetown, Tex.) 84 19182532
1997 Sequence of cDNAs encoding components of vascular actin single-stranded DNA-binding factor 2 establish identity to Puralpha and Purbeta. The Journal of biological chemistry 84 9334258
1995 Transcriptional regulation of human JC polyomavirus promoters by cellular proteins YB-1 and Pur alpha in glial cells. Journal of virology 82 7637031
2014 Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability. Journal of medical genetics 80 25342064
2017 PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature. Journal of medical genetics 72 29097605
1999 Regulation of myelin basic protein gene transcription by Sp1 and Puralpha: evidence for association of Sp1 and Puralpha in brain. Journal of cellular physiology 71 10457364
1998 The single-stranded DNA binding protein, Pur-alpha, binds HIV-1 TAR RNA and activates HIV-1 transcription. Gene 68 9524214
1997 DNA-binding protein Pur alpha and transcription factor YY1 function as transcription activators of the neuron-specific FE65 gene promoter. The Biochemical journal 62 9359867
1989 Effect of a purA mutation on efficacy of Salmonella live-vaccine vectors. Infection and immunity 61 2722244
2008 Androgen receptor overexpression in prostate cancer linked to Pur alpha loss from a novel repressor complex. Cancer research 59 18413735
1999 Reciprocal interaction between two cellular proteins, Puralpha and YB-1, modulates transcriptional activity of JCVCY in glial cells. Molecular and cellular biology 59 10082537
1996 Evidence that replication of human neurotropic JC virus DNA in glial cells is regulated by the sequence-specific single-stranded DNA-binding protein Pur alpha. Journal of virology 59 8648759
2009 X-ray structure of Pur-alpha reveals a Whirly-like fold and an unusual nucleic-acid binding surface. Proceedings of the National Academy of Sciences of the United States of America 58 19846792
1988 Nucleotide sequence and analysis of the purA gene encoding adenylosuccinate synthetase of Escherichia coli K12. The Journal of biological chemistry 58 3058695
1994 Conservation in human and mouse Pur alpha of a motif common to several proteins involved in initiation of DNA replication. Gene 57 7959008
2011 Lack of Pur-alpha alters postnatal brain development and causes megalencephaly. Human molecular genetics 55 22010047
2001 Deletions of PURA, at 5q31, and PURB, at 7p13, in myelodysplastic syndrome and progression to acute myelogenous leukemia. Leukemia 55 11417483
1999 A role for a highly conserved protein of unknown function in regulation of Bacillus subtilis purA by the purine repressor. Journal of bacteriology 55 10368157
1999 Association of HIV-1 Tat with the cellular protein, Puralpha, is mediated by RNA. Proceedings of the National Academy of Sciences of the United States of America 55 10500218
1992 Cloning and sequence of Bacillus subtilis purA and guaA, involved in the conversion of IMP to AMP and GMP. Journal of bacteriology 55 1312531
2015 De novo mutations in PURA are associated with hypotonia and developmental delay. Cold Spring Harbor molecular case studies 54 27148565
2000 The single-stranded DNA- and RNA-binding proteins pur alpha and pur beta link BC1 RNA to microtubules through binding to the dendrite-targeting RNA motifs. Journal of neurochemistry 52 11032866
1998 Interaction of the single-stranded DNA-binding protein Puralpha with the human polyomavirus JC virus early protein T-antigen. The Journal of biological chemistry 52 9830007
1997 Attenuation, persistence, and vaccine potential of an Edwardsiella ictaluri purA mutant. Infection and immunity 52 9353045
2016 Pur-alpha regulates cytoplasmic stress granule dynamics and ameliorates FUS toxicity. Acta neuropathologica 51 26728149
2012 Translation of Pur-α is targeted by cellular miRNAs to modulate the differentiation-dependent susceptibility of monocytes to HIV-1 infection. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 51 22835829
1999 Cell cycle arrest and morphological alterations following microinjection of NIH3T3 cells with Pur alpha. Oncogene 51 10435638
1999 Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1. Oncogene 51 10597240
1997 Transcriptional regulation of neuronal nicotinic acetylcholine receptor genes. A possible role for the DNA-binding protein Puralpha. The Journal of biological chemistry 51 9169473
2001 Cryptic MCAT enhancer regulation in fibroblasts and smooth muscle cells. Suppression of TEF-1 mediated activation by the single-stranded DNA-binding proteins, Pur alpha, Pur beta, and MSY1. The Journal of biological chemistry 48 11751932
2017 PURA, the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions. Gene 46 29221753
2001 Helix-destabilizing properties of the human single-stranded DNA- and RNA-binding protein Puralpha. Journal of cellular biochemistry 46 11169743
2001 Ras-induced colony formation and anchorage-independent growth inhibited by elevated expression of Puralpha in NIH3T3 cells. Journal of cellular biochemistry 46 11329617
2002 hnRNP-K and Pur(alpha) act together to repress the transcriptional activity of the CD43 gene promoter. Blood 45 12411317
2001 Growth inhibition of glioblastoma cells by human Pur(alpha). Journal of cellular physiology 45 11748591
1998 Alterations in Pur(alpha) levels and intracellular localization in the CV-1 cell cycle. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 44 9716182
2001 Coordinate effects of human immunodeficiency virus type 1 protein Tat and cellular protein Puralpha on DNA replication initiated at the JC virus origin. The Journal of general virology 43 11413364
2005 Mechanism of DNA binding and localized strand separation by Pur alpha and comparison with Pur family member, Pur beta. Biochimica et biophysica acta 40 15777841
2002 During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoter. Journal of immunology (Baltimore, Md. : 1950) 40 11937543
1998 Association of Puralpha with RNAs homologous to 7 SL determines its binding ability to the myelin basic protein promoter DNA sequence. The Journal of biological chemistry 40 9712838
2006 A Francisella tularensis subspecies novicida purF mutant, but not a purA mutant, induces protective immunity to tularemia in mice. Vaccine 39 17241711
2001 Functional interaction between cyclin T1/cdk9 and Puralpha determines the level of TNFalpha promoter activation by Tat in glial cells. Journal of neuroimmunology 39 11730934
2016 Structural basis of nucleic-acid recognition and double-strand unwinding by the essential neuronal protein Pur-alpha. eLife 38 26744780
1999 The single-stranded DNA-binding proteins, Puralpha, Purbeta, and MSY1 specifically interact with an exon 3-derived mouse vascular smooth muscle alpha-actin messenger RNA sequence. The Journal of biological chemistry 38 10608902
2000 Neural BC1 RNA associates with pur alpha, a single-stranded DNA and RNA binding protein, which is involved in the transcription of the BC1 RNA gene. Biochemical and biophysical research communications 36 11032728
2021 The Molecular Function of PURA and Its Implications in Neurological Diseases. Frontiers in genetics 35 33777106
2003 The Escherichia coli transcriptional regulator MarA directly represses transcription of purA and hdeA. The Journal of biological chemistry 34 14701822
2000 Interaction of HIV-1 Tat with Puralpha in nuclei of human glial cells: characterization of RNA-mediated protein-protein binding. Journal of cellular biochemistry 34 10679817
2021 PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum. Neurology. Genetics 33 34790866
2006 Nucleoprotein interactions governing cell type-dependent repression of the mouse smooth muscle alpha-actin promoter by single-stranded DNA-binding proteins Pur alpha and Pur beta. The Journal of biological chemistry 32 16436378
2013 A three-gene phylogeny of the Mycena pura complex reveals 11 phylogenetic species and shows ITS to be unreliable for species identification. Fungal biology 30 24295915
2001 Single-stranded nucleic acid-binding protein, Pur alpha, interacts with RNA homologous to 18S ribosomal RNA and inhibits translation in vitro. Journal of cellular biochemistry 28 11596104
1963 FINE STRUCTURE OF MYCOTA : 4. The Occurrence of the Golgi Dictyosome in the Fungus Neobulgaria pura (Fr.) Petrak. The Journal of cell biology 28 19866617
2012 Drosophila Pur-α binds to trinucleotide-repeat containing cellular RNAs and translocates to the early oocyte. RNA biology 27 22614836
2016 Memory deficits, gait ataxia and neuronal loss in the hippocampus and cerebellum in mice that are heterozygous for Pur-alpha. Neuroscience 26 27651147
2012 The Peru Urban versus Rural Asthma (PURA) Study: methods and baseline quality control data from a cross-sectional investigation into the prevalence, severity, genetics, immunology and environmental factors affecting asthma in adolescence in Peru. BMJ open 26 22357570
2015 Pur-alpha functionally interacts with FUS carrying ALS-associated mutations. Cell death & disease 25 26492376
2010 Induction of bicalutamide sensitivity in prostate cancer cells by an epigenetic Puralpha-mediated decrease in androgen receptor levels. The Prostate 25 19790234
2001 During U937 monocytic differentiation repression of the CD43 gene promoter is mediated by the single-stranded DNA binding protein Pur alpha. British journal of haematology 25 11722429
1996 Involvement of a single-stranded DNA binding protein, ssCRE-BP/Pur alpha, in morphine dependence. FEBS letters 25 8706895
2007 Identification of Pur alpha as a new hypoxia response factor responsible for coordinated induction of the beta 2 integrin family. Journal of immunology (Baltimore, Md. : 1950) 24 17641060
2005 Functional interaction of Puralpha with the Cdk2 moiety of cyclin A/Cdk2. Biochemical and biophysical research communications 24 15707957
2004 Pur alpha and Sp8 as opposing regulators of neural gata2 expression. Developmental biology 24 15464585
1997 Evidence for inhibition of MyEF-2 binding to MBP promoter by MEF-1/Pur alpha. Journal of cellular biochemistry 23 9282330
1996 Characterization of the single-strand-specific BPV-1 origin binding protein, SPSF I, as the HeLa Pur alpha factor. Nucleic acids research 23 8759014
2023 Genome-wide CRISPR/Cas9 screening identifies a targetable MEST-PURA interaction in cancer metastasis. EBioMedicine 22 37149929
1975 mut-25, a mutation to mutator linked to purA in Escherichia coli. Journal of bacteriology 22 1089634
2008 The potential role of purine-rich element binding protein (PUR) alpha as a novel treatment target for hormone-refractory prostate cancer. The Prostate 20 18386260
2018 A frame-shift deletion in the PURA gene associates with a new clinical finding: Hypoglycorrhachia. Is GLUT1 a new PURA target? Molecular genetics and metabolism 19 29307761
2018 Exome sequencing identified a de novo mutation of PURA gene in a patient with familial Xp22.31 microduplication. European journal of medical genetics 19 29908350
2015 Long-term follow-up of a patient with 5q31.3 microdeletion syndrome and the smallest de novo 5q31.2q31.3 deletion involving PURA. Molecular cytogenetics 18 26582469
2006 Regulation of the Pur-alpha promoter by E2F-1. Journal of cellular biochemistry 18 16741925
1995 Localization of PURA, the gene encoding the sequence-specific single-stranded-DNA-binding protein Pur alpha, to chromosome band 5q31. Cytogenetics and cell genetics 18 7606931
2014 The Purα/Purβ single-strand DNA-binding proteins attenuate smooth-muscle actin gene transactivation in myofibroblasts. Journal of cellular physiology 17 24446247
2008 Serum response factor neutralizes Pur alpha- and Pur beta-mediated repression of the fetal vascular smooth muscle alpha-actin gene in stressed adult cardiomyocytes. American journal of physiology. Cell physiology 17 18344281
2005 Puralpha activates PDGF-A gene transcription via interactions with a G-rich, single-stranded region of the promoter. Gene 17 15777709
2001 Pur alpha protein implicated in dendritic RNA transport interacts with ribosomes in neuronal cytoplasm. Biological & pharmaceutical bulletin 17 11256476
1999 Association of JC virus large T antigen with myelin basic protein transcription factor (MEF-1/Puralpha) in hypomyelinated brains of mice transgenically expressing T antigen. Journal of virology 17 10364361
2008 C. elegans pur alpha, an activator of end-1, synergizes with the Wnt pathway to specify endoderm. Developmental biology 16 19084000
1999 Self-association of Puralpha is mediated by RNA. Journal of cellular biochemistry 16 10412036
2021 Neonatal PURA syndrome: a case report and literature review. Translational pediatrics 15 33633953
2019 Genetic and environmental risk factors for vitiligo and melanoma in Pura Raza Español horses. Equine veterinary journal 15 30624804
2013 Baculovirus VP1054 is an acquired cellular PURα, a nucleic acid-binding protein specific for GGN repeats. Journal of virology 15 23720732
2007 Lack of association between interleukin-6 promoter polymorphism at position -174 and Henoch-Schönlein pur pura. Clinical and experimental rheumatology 15 17428355
1999 Structural organization and expression of the mouse gene for Pur-1, a highly conserved homolog of the human MAZ gene. European journal of biochemistry 15 10092852
1997 Characterization of a nuclear factor that enhances DNA binding activity of SSCRE-BP/PUR alpha, a single-stranded DNA binding protein. Neurochemistry international 15 9185164
2023 DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-α. The Journal of clinical investigation 14 37909329
2020 PURα mediates epithelial-mesenchymal transition to promote esophageal squamous cell carcinoma progression by regulating Snail2. Cancer letters 14 33144099

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