Affinage

SFPQ

Splicing factor, proline- and glutamine-rich · UniProt P23246

Length
707 aa
Mass
76.1 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SFPQ is a multifunctional nuclear RNA- and DNA-binding protein of the DBHS family that serves as a molecular scaffold for pre-mRNA processing, transcriptional regulation, DNA repair, and RNA transport. It forms obligate homo- and heterodimers with NONO and PSPC1 via an anti-parallel coiled-coil that drives reversible polymerization and liquid–liquid phase separation; this polymerization is essential for nuclear body formation, transcriptional regulation, and can be pathologically triggered by zinc binding (PMID:25765647, PMID:29530979, PMID:32034402). SFPQ is required for spliceosomal catalytic step II, sustains transcriptional elongation of long genes by recruiting CDK9, promotes transcription termination via XRN2 recruitment, suppresses cryptic last exon activation in long introns, and acts as a signal-responsive splicing regulator whose RNA-binding activity is gated by phosphorylation from GSK3, BRK, and SR kinases (PMID:8045264, PMID:29719248, PMID:17639083, PMID:33771997, PMID:20932480, PMID:17188683). Beyond RNA processing, SFPQ participates in DNA double-strand break repair through direct interaction with RAD51D and sequence-independent DNA pairing activity of the SFPQ·NONO complex in c-NHEJ, suppresses TGF-β signaling by phase-separation-mediated sequestration of Smad4, and assembles axonal RNA granules transported by KIF5A/KLC1 kinesin whose disruption causes neurodegeneration linked to ALS and Charcot-Marie-Tooth disease (PMID:20813759, PMID:27924002, PMID:38103553, PMID:27019013, PMID:33284322, PMID:28392072).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    The identity of polypyrimidine-tract-binding splicing factors was unknown; discovery that SFPQ (PSF) binds the polypyrimidine tract and is essential for pre-mRNA splicing — demonstrated by immunodepletion/complementation — established it as a core splicing factor.

    Evidence Bacterially expressed PSF complemented immunodepleted HeLa nuclear extracts to restore splicing

    PMID:8449401

    Open questions at the time
    • Specific step of splicing requiring PSF not yet defined
    • Identity of PSF's RNA target sites beyond polypyrimidine tracts unknown
  2. 1994 High

    Which catalytic step of splicing required PSF was unresolved; UV crosslinking to pre-mRNA within purified C complexes and immunodepletion established that PSF is specifically essential for catalytic step II, potentially replacing U2AF65 at the 3′ splice site.

    Evidence Spliceosomal C-complex purification with UV crosslinking and immunodepletion/complementation

    PMID:8045264

    Open questions at the time
    • Structural basis for PSF at the step II active site unknown
    • Relationship to other step II factors not defined
  3. 1998 High

    Whether PSF had functions beyond splicing was unknown; copurification of PSF with DNA topoisomerase I and p54nrb in a 1:1:1 complex, with 16-fold stimulation of topoisomerase activity, revealed an unexpected role in DNA topology management.

    Evidence Copurification, far Western, and in vitro topoisomerase activity assays

    PMID:10858305 PMID:9756848

    Open questions at the time
    • In vivo relevance of topoisomerase stimulation not shown
    • Whether this relates to transcription or replication unclear
  4. 2001 High

    How PSF regulates transcription independently of splicing was unclear; demonstration that PSF acts as a corepressor of nuclear hormone receptors by recruiting Sin3A/HDACs, and separately localizes to nuclear speckles via RRM2, established PSF as a bifunctional transcriptional and RNA-processing factor with defined domain requirements.

    Evidence Affinity chromatography, reporter assays for TR/RXR corepression; GFP-fusion deletion mutagenesis for speckle localization

    PMID:11161712 PMID:11259580

    Open questions at the time
    • How PSF switches between transcription repression and splicing functions unknown
    • Whether speckle localization is required for splicing function not tested
  5. 2005 High

    How transcription and splicing are coupled through PSF was undefined; the finding that PSF binds both activation domains and the RNA Pol II CTD and stimulates both splicing and 3′-end cleavage in a CTD-dependent manner provided a mechanistic link between transcription and co-transcriptional RNA processing.

    Evidence Affinity chromatography, CTD truncation epistasis, in vitro binding and processing assays

    PMID:16024807

    Open questions at the time
    • Whether PSF directly bridges activator and CTD simultaneously not shown structurally
    • Specificity of target gene selection unknown
  6. 2006 High

    How signaling regulates PSF splicing activity was unknown; identification of SR kinase phosphorylation at the N-terminal RS motif that inhibits polypyrimidine tract binding, and separately GSK3 phosphorylation that gates TRAP150-mediated inhibition of PSF in T cells, established PSF as a signal-responsive splicing regulator.

    Evidence In vitro kinase assays, RNA binding assays, T cell activation systems, co-IP with TRAP150

    PMID:17188683 PMID:19439179 PMID:20932480

    Open questions at the time
    • Combinatorial logic of multiple kinase inputs not resolved
    • Full set of phosphorylation-sensitive splicing targets unknown
  7. 2007 High

    The role of PSF in transcription termination was unknown; demonstration that the p54nrb/PSF heterodimer recruits XRN2 and is required for degradation of 3′-cleaved RNA downstream of poly(A) sites established PSF as a termination factor, while zebrafish genetics revealed in vivo requirement for neuronal survival.

    Evidence In vitro 3′-processing and termination assays, ChIP, siRNA; zebrafish whitesnake mutant characterization

    PMID:17393485 PMID:17639083

    Open questions at the time
    • Whether PSF's termination role is gene-length dependent not yet tested
    • Mechanism of neuronal cell death in zebrafish not defined
  8. 2009 High

    Whether PSF participates in DNA repair was unresolved; direct interaction with RAD51 and stimulation of strand exchange at sub-optimal RAD51 concentrations, plus BRK-mediated cytoplasmic relocalization upon tyrosine phosphorylation, revealed PSF as a regulated participant in the DNA damage response.

    Evidence In vitro strand exchange with purified proteins; mass spectrometry and kinase assays for BRK phosphorylation

    PMID:19439179 PMID:19447914

    Open questions at the time
    • In vivo relevance of RAD51 stimulation not established
    • Whether BRK phosphorylation occurs during DNA damage unknown
  9. 2010 High

    The DNA repair function of SFPQ was incompletely characterized; rapid recruitment to laser-induced DSBs, direct interaction with RAD51D with synthetic lethality, and impaired homology-directed repair upon SFPQ depletion established SFPQ as a bona fide DSB repair factor with roles in both HR and NHEJ.

    Evidence Laser microbeam recruitment, genetic epistasis with RAD51D, HR reporter assays, co-IP with NHEJ proteins

    PMID:20421735 PMID:20813759 PMID:21144806

    Open questions at the time
    • Relative contributions of SFPQ to HR versus NHEJ not quantified
    • Whether DNA repair and splicing functions are separable in vivo unknown
  10. 2015 High

    The structural basis for SFPQ's multivalent scaffolding was unknown; crystal structures revealed an anti-parallel coiled-coil driving infinite polymerization of dimers, preferential SFPQ/PSPC1 heterodimerization, and sequence-independent DNA pairing by the native SFPQ·NONO complex that stimulates DNA-PKcs, establishing the structural foundation for SFPQ's roles in phase separation, nuclear body formation, and c-NHEJ.

    Evidence X-ray crystallography (SFPQ polymer, SFPQ/PSPC1 heterodimer), SAXS, TEM, AUC, DNA pairing/DNA-PKcs assays with purified complex

    PMID:25765647 PMID:25998385 PMID:29530979

    Open questions at the time
    • Full-length SFPQ structure with RNA not available
    • How polymerization is regulated in vivo beyond zinc unknown
  11. 2016 High

    How SFPQ functions in neurons beyond nuclear roles was unclear; demonstration that SFPQ co-assembles target mRNAs into axonal RNA granules and is required for their kinesin-1 (KIF5A/KLC1)-mediated long-distance transport, with disruption causing axon degeneration, established SFPQ as an essential axonal RNA transport adaptor.

    Evidence RNA immunoprecipitation, live axonal transport imaging, KIF5A/KLC1 co-IP, axon degeneration assays in DRG neurons

    PMID:27019013 PMID:33284322

    Open questions at the time
    • Mechanism of SFPQ–kinesin cargo recognition not structurally defined
    • Full repertoire of axonally transported SFPQ-bound mRNAs not catalogued
  12. 2017 High

    How SFPQ supports transcription of long neuronal genes was unknown; co-transcriptional binding to long introns and CDK9 recruitment to sustain elongation, combined with the discovery that SFPQ·NONO substitutes for XLF in c-NHEJ DNA end pairing, unified SFPQ's roles in transcription elongation and DNA repair through its scaffolding capacity.

    Evidence Conditional knockout in mouse brain with long-gene-specific transcriptome defect; CDK9 co-IP; in vitro NHEJ reconstitution showing XLF functional redundancy

    PMID:27924002 PMID:29719248

    Open questions at the time
    • Whether CDK9 recruitment depends on SFPQ polymerization not tested
    • Gene-length threshold for SFPQ dependence not precisely defined
  13. 2017 High

    Whether SFPQ dysfunction contributes to neurodegeneration was speculative; ALS-associated coiled-coil mutations impaired axonal SFPQ localization in zebrafish motor neurons, and SFPQ/FUS co-regulation of Mapt exon 10 splicing linked SFPQ loss to FTLD-like tau pathology, establishing SFPQ as a disease-relevant factor in ALS and tauopathies.

    Evidence Zebrafish rescue with ALS-variant SFPQ constructs; mouse hippocampal SFPQ/FUS knockdown with 4R-tau increase and behavioral rescue

    PMID:28147269 PMID:28392072

    Open questions at the time
    • Causal mutations in SFPQ in human ALS families not identified
    • Mechanism of coiled-coil mutation effect on axonal sorting unknown
  14. 2020 High

    The mechanism linking zinc dyshomeostasis to SFPQ mislocalization was unknown; a 1.94 Å crystal structure revealed zinc coordinates three histidines on SFPQ to drive pathological infinite polymerization and cytoplasmic aggregation in cortical neurons, providing a structural mechanism for SFPQ mislocalization in neurodegeneration.

    Evidence X-ray crystallography of zinc-bound SFPQ, His-to-Ala mutagenesis reducing aggregation in primary neurons

    PMID:32034402

    Open questions at the time
    • Whether zinc-driven polymerization occurs in human ALS tissue not shown
    • Relationship between zinc-driven and coiled-coil-driven polymerization not fully resolved
  15. 2021 High

    How SFPQ loss produces neuronal transcriptome collapse was incompletely understood; discovery that SFPQ suppresses cryptic last exons (CLEs) in long introns — conserved across zebrafish, mouse, and human ALS iPSC neurons — and that CLE-encoded peptides actively interfere with gene function, provided a unifying transcriptomic mechanism for SFPQ-dependent neurodegeneration.

    Evidence RNA-seq in sfpq mutant zebrafish, mouse KO, and human iPSC-derived motor neurons; CRISPR perturbation; CLE-peptide functional assay

    PMID:33476259 PMID:33771997

    Open questions at the time
    • Whether CLE suppression depends on CDK9-mediated elongation not tested
    • Therapeutic targetability of CLE activation not explored
  16. 2023 High

    Whether SFPQ's phase-separation capacity has signaling consequences beyond nuclear body formation was unexplored; demonstration that SFPQ condensates sequester Smad4 via the prion-like domain to suppress TGF-β transcriptional output established SFPQ LLPS as a direct signal-dampening mechanism.

    Evidence In vitro LLPS reconstitution, PrLD mutagenesis, ChIP showing Smad4 exclusion from chromatin, TGF-β reporter assays

    PMID:38103553

    Open questions at the time
    • Generality of SFPQ condensate-mediated signal sequestration to other pathways not tested
    • How TGF-β signaling status feeds back on SFPQ condensate dynamics unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how SFPQ allocates between its splicing, transcription elongation, DNA repair, and RNA transport functions in a single cell; (2) whether SFPQ polymerization states are actively regulated by signaling beyond zinc; (3) the structural basis for SFPQ–RNA target selectivity at full-length resolution; and (4) whether SFPQ mutations are directly causative in human neurodegenerative disease.
  • No full-length SFPQ–RNA co-structure
  • No human Mendelian disease causally attributed to SFPQ mutations
  • Regulation of polymerization state in vivo poorly understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 8 GO:0003677 DNA binding 6 GO:0060090 molecular adaptor activity 5 GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 7 GO:0005829 cytosol 4 GO:0005654 nucleoplasm 3
Pathway
R-HSA-8953854 Metabolism of RNA 10 R-HSA-73894 DNA Repair 7 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2
Partners
CDK9FUSKIF5ANONOPSPC1RAD51DTRAP150XRN2
Complex memberships
SFPQ·NONO heterodimerSFPQ·PSPC1 heterodimerSpliceosomal C complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 SFPQ (PSF) was identified as an essential pre-mRNA splicing factor that binds the polypyrimidine tract of mammalian introns and interacts with PTB (polypyrimidine tract-binding protein). Bacterially synthesized PSF complements immunodepleted extracts to restore splicing activity, and antibody inhibition/immunodepletion experiments demonstrate it is required early in spliceosome formation. In vitro binding assays, immunodepletion, biochemical complementation, antibody inhibition Genes & development High 8449401
1994 PSF is specifically associated with the spliceosomal C complex (post-step I) and is essential for catalytic step II of pre-mRNA splicing. PSF UV crosslinks to pre-mRNA in the purified C complex and may replace U2AF65 at the 3' splice site. Immunodepletion, biochemical complementation, UV crosslinking, spliceosomal complex purification The EMBO journal High 8045264
1998 PSF directly interacts with DNA topoisomerase I, copurifying in a 1:1:1 ratio with topoisomerase I and p54nrb from nuclear extracts. The PSF/p54nrb complex stimulates topoisomerase I activity 16-fold, with recombinant PSF alone providing 5-fold stimulation. Copurification, co-immunoprecipitation, far Western blotting with biotinylated topoisomerase I, in vitro activity assay The Journal of biological chemistry High 9756848
2000 PSF/p54nrb stimulates topoisomerase I 'jumping' between separate DNA helices by enhancing the dissociation of topoisomerase I after ligation, without affecting the individual cleavage or religation half-reactions. In vitro suicide substrate assay, biochemical activity assay Biochemistry High 10858305
2001 PSF acts as a corepressor of type II nuclear hormone receptors (TR and RXR) by interacting with their DNA binding domains (DBDs) and recruiting Sin3A and HDACs to silence transcription. This Sin3A recruitment occurs independently of N-CoR/SMRT. Affinity chromatography, co-immunoprecipitation, luciferase reporter assay, in vivo nuclear receptor assays Molecular and cellular biology High 11259580
2001 PSF localizes to nuclear speckles through a novel pathway dependent on its second RNA recognition motif (RRM2). Deletion of RRM2 abolishes speckle localization; two nuclear localization signals in the C-terminal region are both required for complete nuclear import. PSF redistributes to perinucleolar clusters upon transcription inhibition. GFP fusion live-cell imaging, deletion mutagenesis, transcription inhibitor treatment Experimental cell research High 11161712
2001 During apoptosis, PSF undergoes hyperphosphorylation on serine and threonine residues at its N-terminus, dissociates from PTB, and acquires new binding partners including U1-70K and SR proteins, reorganizing into globular nuclear structures. Immunoprecipitation, GFP-tagged protein imaging, phosphorylation analysis, gel migration analysis Molecular biology of the cell Medium 11514619
2003 PSF (and p54nrb) bind with high affinity to the INS (instability element) region in HIV-1 gag mRNA both in vitro and in vivo, and PSF inhibits expression of INS-containing Rev-dependent HIV-1 transcripts via the INS element. In vitro RNA binding assay, in vivo RNA co-immunoprecipitation, siRNA functional assay Molecular and cellular biology High 12944487
2005 PSF and p54nrb preferentially bind strong transcriptional activation domains and the RNA Pol II CTD, and PSF stimulates splicing and 3'-end cleavage in a manner dependent on the CTD and activation domain. PSF binds CTD in vitro and requires the same domains for both activator binding and pre-mRNA processing stimulation. Affinity chromatography, elevated expression rescue assay, CTD truncation epistasis, in vitro binding Molecular and cellular biology High 16024807
2006 PSF is phosphorylated by SR kinases (human and yeast) both in vivo and in vitro at an isolated RS motif within its N-terminus. This phosphorylation inhibits PSF's binding to the 3' polypyrimidine tract of pre-mRNA. In vivo and in vitro SR kinase phosphorylation assay, RNA binding assay, phospho-specific antibody FEBS letters High 17188683
2007 PSF (as part of the p54nrb/PSF heterodimer) is required for degradation of 3'-cleaved RNA downstream of polyadenylation sites in vitro and for recruitment of the exonuclease XRN2 to facilitate transcription termination. siRNA knockdown of p54nrb leads to defects in XRN2 recruitment and termination. In vitro 3'-processing assay, siRNA knockdown, chromatin immunoprecipitation, co-immunoprecipitation Genes & development High 17639083
2007 In zebrafish, sfpq (whitesnake mutant) is required for cell survival throughout the early embryo and for differentiation of specific classes of brain neurons. Loss of sfpq leads to increased cell death and brain morphology defects, establishing an in vivo requirement for neuronal development. Forward genetic screen, mutant characterization, in vivo loss-of-function in zebrafish Developmental dynamics High 17393485
2007 PSF is recruited to the ESS1 splicing silencer complex in an activation-dependent manner in T cells upon stimulation, accounting for the majority of signal-regulated CD45 exon skipping. PSF and hnRNP L act combinatorially at ESS1. In vitro splicing assay recapitulating signal-induced splicing, complex immunoprecipitation Molecular and cellular biology High 17664280
2009 PSF directly interacts with RAD51 via its N-terminal region. PSF enhances RAD51-mediated homologous pairing and strand exchange at low RAD51 concentrations but inhibits these activities at optimal RAD51 concentrations. The N-terminal region of PSF harbors RAD51- and DNA-binding activities. Direct protein interaction assay, in vitro strand exchange assay, deletion analysis Nucleic acids research High 19447914
2009 BRK (PTK6) tyrosine kinase phosphorylates PSF at C-terminal tyrosines via an SH3 domain-polyproline interaction. Tyrosine phosphorylation of PSF promotes its cytoplasmic relocalization, impairs RNA binding to polypyrimidine sequences, and leads to cell cycle arrest. Mass spectrometry, co-immunoprecipitation, kinase assay, immunofluorescence localization, cell cycle analysis Cellular signalling High 19439179
2010 SFPQ and NONO are rapidly recruited to sites of laser-induced DNA double-strand breaks and are involved in the early DNA damage response. SFPQ depletion delays DSB repair, and SFPQ/NONO co-immunoprecipitate with NHEJ proteins. MATR3 knockdown prolongs SFPQ/NONO retention at damage sites. Laser microbeam DNA damage, live-cell imaging of recruitment, siRNA knockdown, co-immunoprecipitation Cell cycle High 20421735
2010 SFPQ interacts directly with RAD51D and has a synthetic lethal relationship with RAD51D deficiency. SFPQ deficiency alone causes sister chromatid cohesion defects, chromosome instability, and impaired homology-directed DNA repair. Proteomics screen, direct protein interaction, genetic epistasis (synthetic lethality), HR repair assay, cytogenetic analysis Nucleic acids research High 20813759
2010 GSK3 directly phosphorylates PSF in resting T cells, promoting interaction of PSF with TRAP150 and preventing PSF from binding CD45 pre-mRNA. Upon T cell activation, reduced GSK3 activity leads to dephosphorylation of PSF, releasing it from TRAP150, allowing it to bind CD45 splicing regulatory elements and repress exon inclusion. In vitro kinase assay, co-immunoprecipitation, RNA binding assay, T cell activation assays, siRNA knockdown Molecular cell High 20932480
2010 Sequences in the unique N-terminal domain of PSF (SFPQ) are required for radioresistance and for real-time relocalization of PSF-containing complexes to sites of dense laser-induced DNA damage in living cells. PSF drives relocalization of PSPC1 to damage sites. miRNA-mediated knockdown with genetic rescue, live-cell imaging of relocalization, deletion/mutation analysis DNA repair Medium 21144806
2010 Fox-3 interacts with PSF (identified by affinity chromatography), and PSF functions as a coactivator of Fox-3-dependent alternative splicing of NMHC II-B N30 exon. PSF enhances N30 inclusion in a UGCAUG-dependent manner without directly binding this element, and Fox-3 recruitment to UGCAUG requires PSF. Affinity chromatography, co-immunoprecipitation, in vivo splicing assays, RIP Nucleic acids research Medium 21177649
2010 PSF acts as a repressor of STAT6-mediated Igε gene transcription by interacting with STAT6 (after IL-4-induced tyrosine phosphorylation of both proteins) and recruiting HDAC1 to the STAT6 transcription complex, reducing H3 acetylation at promoter regions. Proteomic identification, co-immunoprecipitation, luciferase reporter, ChIP, HDAC inhibitor rescue The Journal of biological chemistry Medium 21106524
2011 SFPQ/PSF is a host factor essential for influenza virus transcription; it increases the efficiency of viral mRNA polyadenylation. siRNA knockdown reduces viral mRNA, cRNA, and vRNA by >5-fold and impairs polyadenylation in in vitro transcription assays with recombinant RNPs. siRNA knockdown, in vitro transcription assay, viral RNA quantification, proteomic identification of polymerase-associated host proteins PLoS pathogens High 22114566
2014 NEAT1 lncRNA induction relocates SFPQ from the IL8 gene promoter to paraspeckles upon viral infection or TLR3-p38 pathway stimulation, thereby de-repressing IL8 transcription. SFPQ normally acts as a transcriptional repressor at the IL8 promoter. ChIP, RNA FISH, knockdown/overexpression functional assays, NEAT1 induction by virus/poly I:C Molecular cell High 24507715
2014 MALAT1 lncRNA binds SFPQ, releasing PTBP2 (oncogene) from the SFPQ/PTBP2 complex, leading to increased free PTBP2 that promotes CRC cell proliferation and migration. RNA pulldown, co-immunoprecipitation, functional proliferation/migration assays British journal of cancer Medium 25025966
2014 p54nrb/NonO and PSF (likely as a heterodimer) stimulate U snRNA nuclear export by accelerating recruitment of PHAX and subsequently CRM1/Ran onto RNA substrates in vitro, thereby mediating efficient U snRNA export in vivo. In vitro export complex assembly assay, in vivo export assay, knockdown Nucleic acids research High 24413662
2015 Crystal structure of SFPQ reveals an anti-parallel coiled-coil that mediates infinite linear polymerization of SFPQ dimers. Polymerization is reversible in solution and can be templated by DNA. Disruption of the coiled-coil interaction motif causes SFPQ mislocalization, reduced nuclear body formation, abrogated molecular interactions, and deficient transcriptional regulation. X-ray crystallography, SAXS, TEM, mutagenesis, functional cell-based assays Nucleic acids research High 25765647
2015 SFPQ is asymmetrically dimethylated at multiple N-terminal arginine residues by PRMT1 in vitro. Arginine methylation increases SFPQ association with mRNA in mRNP complexes. Citrullination of SFPQ antagonizes arginine methylation. Neither modification affects SFPQ/NONO complex formation. Mass spectrometry, in vitro methylation assay, mRNP immunoprecipitation RNA High 25605962
2015 TRAP150 binds PSF via a PSF-interacting domain (PID) that encompasses the RNA recognition motifs (RRMs). TRAP150's PID directly inhibits interaction of PSF RRMs with RNA through RRM2, without affecting PSF dimerization with other DBHS proteins. TRAP150 antagonizes PSF splicing activity toward ~40 T cell splicing events. Biochemical binding assays, deletion/mutation mapping, RASL-Seq splicing analysis, co-immunoprecipitation Nucleic acids research High 26261210
2016 SFPQ binds and co-assembles multiple mRNAs (including LaminB2 and Bclw) into RNA granules in dorsal root ganglion neurons and is required for axonal trafficking of these mRNAs. SFPQ acts in nuclei, cytoplasm, and axons to regulate an RNA regulon essential for neurotrophin-dependent axonal viability. RNA immunoprecipitation, live-cell imaging, RNA granule co-assembly assay, loss-of-function with axonal degeneration readout Nature neuroscience High 27019013
2017 SFPQ is required for cytoplasmic/axonal localization in motor neurons; the coiled-coil domain is required for axonal localization of SFPQ. ALS-associated coiled-coil domain mutations specifically impair axonal SFPQ localization and alter motor axon morphology in zebrafish. Zebrafish sfpq null mutant rescue with cytosolic SFPQ construct, ALS variant expression, in vivo imaging Neuron High 28392072
2017 FUS and SFPQ interact in neuronal nuclei to regulate alternative splicing of Mapt exon 10, controlling the ratio of 4R-tau to 3R-tau. Loss of FUS or SFPQ increases 4R/3R-tau ratio, causing FTLD-like behaviors and neuropathology in mice. Co-immunoprecipitation, hippocampus-specific knockdown in mice, alternative splicing analysis, behavioral assays, rescue by tau isoform-specific silencing Cell reports High 28147269
2017 Sfpq co-transcriptionally binds long introns and is required for sustaining transcriptional elongation of long genes (>100 kb) by mediating the interaction of CDK9 with the elongation complex. Sfpq disruption in mouse brain causes neuronal apoptosis and specific downregulation of long neuronal genes. RIP, ChIP, CDK9 co-immunoprecipitation, Sfpq conditional knockout in mouse brain, transcriptome analysis Cell reports High 29719248
2017 Nucleoplasmic Sfpq interacts with Ago2 in an RNA-dependent manner and controls miRNA targeting of a subset of mRNA binding sites by locally binding long 3'UTRs. Sfpq forms aggregates on long 3'UTRs to optimize miRNA positioning at selected sites. Quantitative proteomics (Ago2 interactome), HITS-CLIP, transcriptomic analysis, let-7a/Lin28A functional validation Nature communications High 29084942
2017 The SFPQ·NONO complex substitutes in vitro for the core c-NHEJ factor XLF, promoting sequence-independent DNA end pairing. SFPQ·NONO and XLF function redundantly in vitro but both are required for efficient end joining and radioresistance in cell-based assays. In vitro end joining assay, shRNA knockdown, radioresistance assay Nucleic acids research High 27924002
2018 Crystal structure of SFPQ/PSPC1 heterodimer at 2.3 Å resolution reveals structural basis for preferential heterodimerization. Analytical ultracentrifugation shows SFPQ-containing heterodimers dissociate at low micromolar concentrations with higher affinity than homodimer; SFPQ/PSPC1 heterodimer has >6-fold lower Kd than SFPQ/NONO. X-ray crystallography, analytical ultracentrifugation The Journal of biological chemistry High 29530979
2019 SFPQ and NONO locate at telomeres and suppress RNA:DNA hybrid (R-loop) formation and replication defects at telomeres. SFPQ/NONO act as heterodimers: NONO suppresses telomere fragility while SFPQ suppresses homologous recombination at telomeres. ChIP, R-loop immunoprecipitation (S9.6 antibody), telomere FISH, SFPQ/NONO knockdown Nature communications High 30824709
2020 SFPQ directly interacts with FTO (the m6A demethylase) and facilitates FTO's substrate preference by recruiting FTO to specific m6A sites on target transcripts, as overexpression of SFPQ leads to demethylation of adjacent m6As. Genetically encoded photocrosslinking (site-specific), co-immunoprecipitation, m6A mapping Cell chemical biology Medium 31981477
2020 SFPQ, in complex with p54nrb, binds SRSF2 under platinum treatment and decreases SRSF2 binding to caspase-9 RNA, thereby favoring expression of an antiapoptotic caspase-9 splice form and protecting cancer cells from platinum-induced death. Co-immunoprecipitation, RNA immunoprecipitation, splicing analysis, cell death assays Oncogene Medium 32332923
2020 SFPQ depletion in BRAFV600E colorectal cancer cells triggers the Chk1-dependent replication checkpoint, decreases replication factory numbers and activity, and increases collision between replication and transcription, resulting in synthetic lethality. shRNA loss-of-function screen, Chk1 checkpoint assay, replication factory imaging, transcription-replication collision assay Cell reports Medium 32966782
2020 Zinc binds to three histidine residues on SFPQ and drives infinite polymerization of SFPQ through intermolecular interactions revealed by crystal structure at 1.94 Å. Zinc application induces cytoplasmic aggregation of SFPQ in primary cortical neurons, which is reduced by mutagenesis of zinc-coordinating histidines. X-ray crystallography, mutagenesis, primary neuron zinc treatment, immunofluorescence Nucleic acids research High 32034402
2021 SFPQ-RNA granules bind selectively to a tetrameric kinesin containing KIF5A and KLC1 for long-distance axonal transport. SFPQ binding to KIF5A/KLC1 is required for axon survival and is disrupted by CMT disease-causing KIF5A mutations. Co-immunoprecipitation, live axonal transport imaging, KIF5A CMT mutant analysis, axon degeneration assay The Journal of cell biology High 33284322
2021 Loss of SFPQ leads to premature transcription termination via widespread activation of cryptic last exons (CLEs) in long introns of neuronal genes. SFPQ-inhibited CLEs can produce short peptides that interfere with normal gene function, as demonstrated for an epha4b CLE-encoded peptide causing neurodevelopmental defects in zebrafish. RNA-seq in sfpq mutant zebrafish, mouse, and human ALS iPSC neurons; CRISPR perturbation; peptide functional rescue assay Nature communications High 33771997
2021 SFPQ depletion leads to increased intron retention with concomitant cryptic splicing, premature transcription termination, and polyadenylation, particularly for long introns, and disrupts biogenesis of a specific class of circRNAs with distal inverted Alu elements (DALI circRNAs). siRNA knockdown, RNA-seq, circRNA profiling eLife Medium 33476259
2022 MALAT1 stabilizes the interaction between PTBP1 and PSF, forming a functional module that affects a network of alternative splicing events. MALAT1 also stabilizes PSF interactions with several other hnRNP proteins. Co-immunoprecipitation, splicing analysis, RNA pulldown Science advances Medium 36563164
2023 SFPQ suppresses TGF-β signaling by sequestering Smad4 within SFPQ condensates via liquid-liquid phase separation driven by its prion-like domain (PrLD). This excludes Smad4 from Smad complexes and chromatin, dampening Smad-dependent transcription. SFPQ deficiency or loss of phase separation renders cells hypersensitive to TGF-β. Co-immunoprecipitation, LLPS assay, ChIP, PrLD mutagenesis, TGF-β reporter assay, Smad4 chromatin occupancy Developmental cell High 38103553
2015 The native SFPQ·NONO complex binds DNA independently of free DNA ends, has intrinsic DNA pairing activity, and stimulates DNA-dependent protein kinase autophosphorylation, consistent with promoting synaptic pre-ligation complex formation during NHEJ without occluding DNA termini. Purified native complex, microwell-based DNA binding and pairing assay, DNA-PKcs autophosphorylation assay Biochemical and biophysical research communications High 25998385

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli. Molecular cell 556 24507715
1993 Cloning and characterization of PSF, a novel pre-mRNA splicing factor. Genes & development 334 8449401
2014 Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. British journal of cancer 326 25025966
2002 PSF and p54(nrb)/NonO--multi-functional nuclear proteins. FEBS letters 297 12417296
2016 The DBHS proteins SFPQ, NONO and PSPC1: a multipurpose molecular scaffold. Nucleic acids research 268 27084935
1994 A novel set of spliceosome-associated proteins and the essential splicing factor PSF bind stably to pre-mRNA prior to catalytic step II of the splicing reaction. The EMBO journal 204 8045264
2010 Involvement of Matrin 3 and SFPQ/NONO in the DNA damage response. Cell cycle (Georgetown, Tex.) 182 20421735
2001 PSF is a novel corepressor that mediates its effect through Sin3A and the DNA binding domain of nuclear hormone receptors. Molecular and cellular biology 153 11259580
2007 The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3' processing and transcription termination. Genes & development 151 17639083
2015 The structure of human SFPQ reveals a coiled-coil mediated polymer essential for functional aggregation in gene regulation. Nucleic acids research 132 25765647
2016 The RNA-binding protein SFPQ orchestrates an RNA regulon to promote axon viability. Nature neuroscience 126 27019013
2018 Intron retention and nuclear loss of SFPQ are molecular hallmarks of ALS. Nature communications 124 29789581
2003 PSF acts through the human immunodeficiency virus type 1 mRNA instability elements to regulate virus expression. Molecular and cellular biology 115 12944487
2010 Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing. Molecular cell 106 20932480
2005 Role for PSF in mediating transcriptional activator-dependent stimulation of pre-mRNA processing in vivo. Molecular and cellular biology 103 16024807
2010 The splicing-factor related protein SFPQ/PSF interacts with RAD51D and is necessary for homology-directed repair and sister chromatid cohesion. Nucleic acids research 101 20813759
2014 Jak/Stat signaling stimulates zebrafish optic nerve regeneration and overcomes the inhibitory actions of Socs3 and Sfpq. The Journal of neuroscience : the official journal of the Society for Neuroscience 100 24523552
2019 SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability. Nature communications 99 30824709
2001 An RNA recognition motif (RRM) is required for the localization of PTB-associated splicing factor (PSF) to subnuclear speckles. Experimental cell research 94 11161712
2009 Perivascular epithelioid cell tumor with SFPQ/PSF-TFE3 gene fusion in a patient with advanced neuroblastoma. The American journal of surgical pathology 93 19606011
2017 Altered Tau Isoform Ratio Caused by Loss of FUS and SFPQ Function Leads to FTLD-like Phenotypes. Cell reports 89 28147269
2015 2'-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF. Nucleic acids research 87 25855809
2012 Tau-mediated nuclear depletion and cytoplasmic accumulation of SFPQ in Alzheimer's and Pick's disease. PloS one 83 22558197
2021 The RNA-binding protein SFPQ preserves long-intron splicing and regulates circRNA biogenesis in mammals. eLife 80 33476259
2017 SFPQ•NONO and XLF function separately and together to promote DNA double-strand break repair via canonical nonhomologous end joining. Nucleic acids research 79 27924002
1998 The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity by a direct interaction. The Journal of biological chemistry 79 9756848
2006 PSPC1, NONO, and SFPQ are expressed in mouse Sertoli cells and may function as coregulators of androgen receptor-mediated transcription. Biology of reproduction 78 16641145
2010 Fox-3 and PSF interact to activate neural cell-specific alternative splicing. Nucleic acids research 76 21177649
2018 Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain. Cell reports 72 29719248
2016 Senescence-specific change in ROS scavenging enzyme activities and regulation of various SOD isozymes to ROS levels in psf mutant rice leaves. Plant physiology and biochemistry : PPB 70 27756006
2011 The splicing factor proline-glutamine rich (SFPQ/PSF) is involved in influenza virus transcription. PLoS pathogens 70 22114566
2019 IGFBP-3 interacts with NONO and SFPQ in PARP-dependent DNA damage repair in triple-negative breast cancer. Cellular and molecular life sciences : CMLS 69 30725116
2015 PSF: nuclear busy-body or nuclear facilitator? Wiley interdisciplinary reviews. RNA 69 25832716
1984 Purification of a novel pancreatic secretory factor (PSF) and a novel peptide with VIP- and secretin-like properties (helodermin) from Gila monster venom. FEBS letters 69 6692928
2017 Post-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq. Nature communications 68 29084942
2007 Combinatorial control of signal-induced exon repression by hnRNP L and PSF. Molecular and cellular biology 67 17664280
2020 SFPQ and Tau: critical factors contributing to rapid progression of Alzheimer's disease. Acta neuropathologica 66 32577828
2020 The Emerging Role of the RNA-Binding Protein SFPQ in Neuronal Function and Neurodegeneration. International journal of molecular sciences 64 32998269
2016 Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO. Oncotarget 63 27259250
2010 Sequences in PSF/SFPQ mediate radioresistance and recruitment of PSF/SFPQ-containing complexes to DNA damage sites in human cells. DNA repair 60 21144806
2008 The complex of TFII-I, PARP1, and SFPQ proteins regulates the DYX1C1 gene implicated in neuronal migration and dyslexia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 59 18445785
2020 Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity. Oncogene 58 32332923
2009 Human PSF binds to RAD51 and modulates its homologous-pairing and strand-exchange activities. Nucleic acids research 58 19447914
2007 Whitesnake/sfpq is required for cell survival and neuronal development in the zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 57 17393485
2021 Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival. The Journal of cell biology 55 33284322
2009 BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest. Cellular signalling 55 19439179
2012 Annexin A2 and PSF proteins interact with p53 IRES and regulate translation of p53 mRNA. RNA biology 54 23131771
2017 Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development. Neuron 53 28392072
2001 Nuclear relocalization of the pre-mRNA splicing factor PSF during apoptosis involves hyperphosphorylation, masking of antigenic epitopes, and changes in protein interactions. Molecular biology of the cell 52 11514619
2009 Melanotic Xp11 translocation renal cancer: a case with PSF-TFE3 gene fusion and up-regulation of melanogenetic transcripts. The American journal of surgical pathology 50 19809274
2022 MALAT1 modulates alternative splicing by cooperating with the splicing factors PTBP1 and PSF. Science advances 48 36563164
2000 Differential nuclear localization and nuclear matrix association of the splicing factors PSF and PTB. Journal of cellular biochemistry 48 10653975
2012 HIV-1 pre-mRNA commitment to Rev mediated export through PSF and Matrin 3. Virology 46 23158102
2009 hnRNP M interacts with PSF and p54(nrb) and co-localizes within defined nuclear structures. Experimental cell research 46 19874820
2015 Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA. RNA (New York, N.Y.) 44 25605962
2008 The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1. Genes, chromosomes & cancer 44 18205209
2006 Binding of the polypyrimidine tract-binding protein-associated splicing factor (PSF) to the hepatitis delta virus RNA. Virology 40 16938326
2022 Long noncoding RNA LHFPL3-AS2 suppresses metastasis of non-small cell lung cancer by interacting with SFPQ to regulate TXNIP expression. Cancer letters 39 35101541
2020 PSF Promotes ER-Positive Breast Cancer Progression via Posttranscriptional Regulation of ESR1 and SCFD2. Cancer research 39 32213542
1998 The snRNP-free U1A (SF-A) complex(es): identification of the largest subunit as PSF, the polypyrimidine-tract binding protein-associated splicing factor. RNA (New York, N.Y.) 39 9848648
2000 PSF/p54(nrb) stimulates "jumping" of DNA topoisomerase I between separate DNA helices. Biochemistry 38 10858305
2018 Crystal structure of a SFPQ/PSPC1 heterodimer provides insights into preferential heterodimerization of human DBHS family proteins. The Journal of biological chemistry 37 29530979
2013 Characterization and complete genome sequence of the Shigella bacteriophage pSf-1. Research in microbiology 36 24012542
2020 SFPQ Is an FTO-Binding Protein that Facilitates the Demethylation Substrate Preference. Cell chemical biology 34 31981477
2020 Long non-coding RNA ARAP1-AS1 promotes tumorigenesis and metastasis through facilitating proto-oncogene c-Myc translation via dissociating PSF/PTB dimer in cervical cancer. Cancer medicine 33 31953923
2010 Development and characterization of a new epithelial cell line PSF from caudal fin of Green chromide, Etroplus suratensis (Bloch, 1790). In vitro cellular & developmental biology. Animal 33 20577829
2007 Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation. Learning & memory (Cold Spring Harbor, N.Y.) 33 17911373
2012 Vimentin and PSF act in concert to regulate IbeA+ E. coli K1 induced activation and nuclear translocation of NF-κB in human brain endothelial cells. PloS one 32 22536447
2014 p54nrb/NonO and PSF promote U snRNA nuclear export by accelerating its export complex assembly. Nucleic acids research 31 24413662
2011 Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 31 21507896
2009 Hacking RNA: Hakai promotes tumorigenesis by enhancing the RNA-binding function of PSF. Cell cycle (Georgetown, Tex.) 31 19855157
2020 SFPQ Depletion Is Synthetically Lethal with BRAFV600E in Colorectal Cancer Cells. Cell reports 30 32966782
2003 PSF-TFE3 oncoprotein in papillary renal cell carcinoma inactivates TFE3 and p53 through cytoplasmic sequestration. Oncogene 30 12902986
2020 AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma. Oncogene 29 32661324
2018 NEAT1_2-SFPQ axis mediates cisplatin resistance in liver cancer cells in vitro. OncoTargets and therapy 29 30254462
2022 Loss of NPPA-AS1 promotes heart regeneration by stabilizing SFPQ-NONO heteromer-induced DNA repair. Basic research in cardiology 28 35247074
2021 SFPQ promotes an oncogenic transcriptomic state in melanoma. Oncogene 28 34218270
2020 Aberrant interaction between FUS and SFPQ in neurons in a wide range of FTLD spectrum diseases. Brain : a journal of neurology 28 32770214
2015 Characterization of DNA binding and pairing activities associated with the native SFPQ·NONO DNA repair protein complex. Biochemical and biophysical research communications 28 25998385
2022 Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models. Nature methods 27 35577958
2019 A novel human lncRNA SANT1 cis-regulates the expression of SLC47A2 by altering SFPQ/E2F1/HDAC1 binding to the promoter region in renal cell carcinoma. RNA biology 27 30951404
1999 Identification of PSF, the polypyrimidine tract-binding protein-associated splicing factor, as a developmentally regulated neuronal protein. Journal of neuroscience research 27 10397636
2023 PsRGL1 negatively regulates chilling- and gibberellin-induced dormancy release by PsF-box1-mediated targeting for proteolytic degradation in tree peony. Horticulture research 26 37786434
2023 Smad4 sequestered in SFPQ condensates prevents TGF-β tumor-suppressive signaling. Developmental cell 26 38103553
2015 Interaction and colocalization of HERMES/RBPMS with NonO, PSF, and G3BP1 in neuronal cytoplasmic RNP granules in mouse retinal line cells. Genes to cells : devoted to molecular & cellular mechanisms 26 25651939
2020 Structural basis of the zinc-induced cytoplasmic aggregation of the RNA-binding protein SFPQ. Nucleic acids research 25 32034402
2006 The splicing factor PSF is part of a large complex that assembles in the absence of pre-mRNA and contains all five snRNPs. RNA biology 25 17114945
2021 A conserved role for the ALS-linked splicing factor SFPQ in repression of pathogenic cryptic last exons. Nature communications 24 33771997
2018 MicroRNA-1296 Facilitates Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Targeting SFPQ. Journal of Cancer 24 30026827
2017 Depletion of NEAT1 lncRNA attenuates nucleolar stress by releasing sequestered P54nrb and PSF to facilitate c-Myc translation. PloS one 24 28288210
2019 Loss of RNA-Binding Protein Sfpq Causes Long-Gene Transcriptopathy in Skeletal Muscle and Severe Muscle Mass Reduction with Metabolic Myopathy. iScience 23 30870781
2015 TRAP150 interacts with the RNA-binding domain of PSF and antagonizes splicing of numerous PSF-target genes in T cells. Nucleic acids research 23 26261210
2013 PTB-associated splicing factor (PSF) is a PPARγ-binding protein and growth regulator of colon cancer cells. PloS one 23 23516550
2010 PTB-associated splicing factor (PSF) functions as a repressor of STAT6-mediated Ig epsilon gene transcription by recruitment of HDAC1. The Journal of biological chemistry 23 21106524
2007 PSF is an IbeA-binding protein contributing to meningitic Escherichia coli K1 invasion of human brain microvascular endothelial cells. Medical microbiology and immunology 23 17318576
2018 Dysregulation and Dislocation of SFPQ Disturbed DNA Organization in Alzheimer's Disease and Frontotemporal Dementia. Journal of Alzheimer's disease : JAD 21 29376859
2021 ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ. Human molecular genetics 20 33729478
2015 Isolation and Comparative Genomic Analysis of T1-Like Shigella Bacteriophage pSf-2. Current microbiology 20 26612033
2006 Role of PSF-TFE3 oncoprotein in the development of papillary renal cell carcinomas. Oncogene 20 16832349
2006 Phosphorylation by SR kinases regulates the binding of PTB-associated splicing factor (PSF) to the pre-mRNA polypyrimidine tract. FEBS letters 20 17188683