| 2015 |
Crystal structure of human SFPQ reveals it forms an extended linear polymer (>265 Å long) via an anti-parallel coiled-coil domain. This polymerization is reversible in solution and can be templated by DNA. Disruptive mutation of the coiled-coil interaction motif causes SFPQ mislocalization, reduced nuclear body formation, abrogated molecular interactions, and deficient transcriptional regulation, demonstrating that polymerization is essential for SFPQ cellular function. |
X-ray crystallography, small-angle X-ray scattering (SAXS), transmission electron microscopy, site-directed mutagenesis, cellular localization assays |
Nucleic acids research |
High |
25765647
|
| 2014 |
SFPQ acts as a transcriptional repressor of IL8 by binding its promoter. Upon induction of lncRNA NEAT1 by viral infection or TLR3-p38 pathway stimulation, SFPQ is relocalized from the IL8 promoter to paraspeckles, thereby de-repressing IL8 transcription as part of the innate immune response. |
Chromatin immunoprecipitation, siRNA knockdown, NEAT1 overexpression/induction, immunofluorescence, reporter assays |
Molecular cell |
High |
24507715
|
| 2018 |
SFPQ is required for transcriptional elongation of long genes (>100 kb) by RNA polymerase II. SFPQ co-transcriptionally binds long introns and mediates interaction of CDK9 with the elongation complex. Loss of SFPQ in developing mouse brains causes specific downregulation of long neuronal genes and neuronal apoptosis. |
CLIP-seq, ChIP-seq, mouse conditional knockout, RNA-seq, co-immunoprecipitation |
Cell reports |
High |
29719248
|
| 2016 |
SFPQ functions as an RNA-binding protein that orchestrates an RNA regulon in dorsal root ganglion neurons, binding and co-assembling LaminB2 (Lmnb2) and Bclw (Bcl2l2) mRNAs into RNA granules and trafficking them to axons. SFPQ is required in nuclei, cytoplasm, and axons; its loss abolishes axonal transport of these mRNAs and causes neurotrophin-dependent axon degeneration. |
RIP, CLIP, fluorescence imaging, siRNA knockdown in neurons, in vivo mouse DRG experiments |
Nature neuroscience |
High |
27019013
|
| 2021 |
SFPQ is required for accurate splicing of long introns and suppresses premature cleavage/polyadenylation events. SFPQ depletion leads to increased intron retention, cryptic splicing, premature transcription termination, and polyadenylation preferentially in long introns. SFPQ also suppresses the activation of cryptic last exons (CLEs) in neuronal genes. |
RNA-seq, SFPQ knockdown, bioinformatic analysis of splicing events across human, mouse, and zebrafish |
eLife |
High |
33476259 33771997
|
| 2010 |
SFPQ (PSF) directly interacts with RAD51D and promotes homology-directed DNA repair. Deficiency of SFPQ alone causes sister chromatid cohesion defects and chromosome instability. SFPQ depletion delays DSB repair, and combined deficiency with RAD51D is synthetically lethal. |
Co-immunoprecipitation, siRNA knockdown, sister chromatid cohesion assay, DNA repair assays (comet, γH2AX) |
Nucleic acids research |
Medium |
20813759
|
| 2010 |
The SFPQ/NONO heterodimer is rapidly recruited to laser-induced DNA double-strand break sites. SFPQ depletion delays DSB repair. MATR3 knockdown prolongs SFPQ/NONO retention at damage sites. Non-homologous end-joining proteins co-immunoprecipitate with NONO. |
Laser microbeam irradiation, live-cell imaging, siRNA knockdown, co-immunoprecipitation, cell cycle analysis |
Cell cycle (Georgetown, Tex.) |
Medium |
20421735
|
| 2017 |
SFPQ•NONO complex promotes canonical non-homologous end joining (c-NHEJ) by substituting for XLF in vitro, promoting sequence-independent pairing of DNA substrates. In cell-based assays, NONO and XLF are both required for efficient end joining and radioresistance, indicating partly distinct functions. SFPQ•NONO complex also promotes DNA-PKcs autophosphorylation. |
In vitro end-joining assay, shRNA knockdown, radioresistance assay, DNA-PKcs autophosphorylation assay |
Nucleic acids research |
High |
27924002
|
| 2015 |
The SFPQ•NONO complex binds DNA independently of free ends (unlike Ku), has DNA pairing/synapsis activity, and stimulates DNA-PKcs autophosphorylation. These activities support a model where SFPQ•NONO binds internal DNA sequences to stabilize a pre-ligation synaptic complex in NHEJ. |
Microwell-based DNA binding/pairing assay, in vitro DNA-PKcs autophosphorylation assay, native SFPQ•NONO purified from HeLa cells |
Biochemical and biophysical research communications |
High |
25998385
|
| 2015 |
SFPQ is asymmetrically dimethylated at multiple arginines in its N-terminal domain by PRMT1. This arginine methylation increases SFPQ's association with mRNA in mRNP complexes. Citrullination of SFPQ antagonizes arginine methylation. Neither modification affects SFPQ/NONO complex formation. |
Mass spectrometry of endogenous complex, in vitro methylation assay with PRMT1, mRNP immunoprecipitation |
RNA (New York, N.Y.) |
High |
25605962
|
| 2017 |
FUS and SFPQ interact in the nucleus to regulate alternative splicing of Mapt exon 10, controlling the ratio of 4-repeat tau (4R-T) to 3-repeat tau (3R-T). Hippocampus-specific knockdown of either FUS or SFPQ increases the 4R-T/3R-T ratio, causing FTLD-like behaviors, neuronal loss, and tau phosphorylation. Normalization of tau isoform ratio rescues the phenotype. |
Co-immunoprecipitation, in vivo shRNA knockdown in mouse hippocampus, RT-PCR for splice isoforms, behavioral testing |
Cell reports |
High |
28147269
|
| 2021 |
SFPQ-RNA granules are transported anterogradely in axons by a tetrameric kinesin complex containing the motor KIF5A and adaptor KLC1. The SFPQ-KIF5A/KLC1 interaction is required for axon survival. KIF5A mutations causing Charcot-Marie-Tooth disease impair this binding. |
Co-immunoprecipitation, live imaging of RNA granule transport, genetic mouse model, CMT disease mutations |
The Journal of cell biology |
High |
33284322
|
| 2017 |
SFPQ localizes to motor axons (in addition to nuclei) in zebrafish. Expression of a cytoplasmic-only SFPQ construct rescues motor axon defects and motility in sfpq null zebrafish. ALS-linked variants in the coiled-coil domain specifically impair axonal localization of SFPQ without rescuing axon morphology, demonstrating a functional requirement for axonal SFPQ. |
Zebrafish null mutant, rescue with cytoplasmic SFPQ construct, fluorescence imaging, ALS patient-derived variant analysis |
Neuron |
High |
28392072
|
| 2019 |
SFPQ and NONO locate at telomeres and suppress RNA:DNA hybrid (R-loop) formation, telomere fragility, and homologous recombination at telomeres. SFPQ and NONO act as heterodimers in this function; their combined loss causes massive telomere recombination events in ALT cells. |
ChIP, R-loop detection (DRIP assay), telomere FISH, siRNA knockdown, co-immunoprecipitation |
Nature communications |
High |
30824709
|
| 2020 |
SFPQ binds FTO (the m6A demethylase) directly via site-specific photocrosslinking. Overexpression of SFPQ promotes demethylation of m6A residues adjacent to SFPQ-binding sites across the transcriptome, indicating SFPQ recruits FTO to specific RNA targets to modulate their m6A status. |
Genetically encoded photocrosslinking, transcriptome-wide m6A profiling, SFPQ overexpression |
Cell chemical biology |
Medium |
31981477
|
| 2017 |
Nucleoplasmic SFPQ interacts with Ago2 in an RNA-dependent manner and directly controls miRNA targeting of a subset of mRNAs by local binding. SFPQ binds long 3'-UTRs to form aggregates that optimize miRNA positioning/recruitment at selected binding sites, including let-7a binding to Lin28A 3'-UTR, extending miRNA-mediated silencing into the nucleoplasm. |
Quantitative proteomics, HITS-CLIP, transcriptomics, RNA immunoprecipitation, dual-luciferase reporter |
Nature communications |
High |
29084942
|
| 2020 |
SFPQ in complex with p54nrb (NONO) binds and modulates SRSF2 splicing factor activity under platinum treatment in ovarian cancer cells. The SFPQ/NONO complex decreases SRSF2 binding to caspase-9 RNA, favoring expression of its antiapoptotic alternatively spliced form and promoting platinum resistance. |
Co-immunoprecipitation, RNA-IP, siRNA knockdown, alternative splicing analysis |
Oncogene |
Medium |
32332923
|
| 2011 |
SFPQ (PSF) is an essential host factor for influenza A virus transcription. SFPQ knockdown reduces viral mRNA, cRNA, and vRNA accumulation >5-fold and specifically impairs polyadenylation of viral mRNAs without affecting cap-snatching, demonstrating SFPQ increases the efficiency of viral mRNA polyadenylation. |
siRNA knockdown, in vitro transcription of recombinant RNPs, virus yield assay, RNA accumulation analysis |
PLoS pathogens |
High |
22114566
|
| 2010 |
PSF (SFPQ) contributes to radioresistance in human cells. The N-terminal domain of PSF is specifically required for both radioresistance and real-time relocalization of PSF-containing complexes to sites of laser-induced DNA damage. PSF, not its dimerization partner NONO, drives this relocalization. |
miRNA-mediated PSF knockdown, genetic rescue with PSF mutants, live-cell imaging of laser-induced DNA damage sites |
DNA repair |
Medium |
21144806
|
| 2020 |
Zinc binding to SFPQ induces infinite polymerization via intermolecular interactions revealed by a 1.94 Å crystal structure. Application of zinc to primary cortical neurons induces cytoplasmic accumulation and aggregation of SFPQ. Mutagenesis of the three zinc-coordinating histidine residues reduces zinc-binding affinity and abolishes zinc-induced cytoplasmic aggregation. |
X-ray crystallography, site-directed mutagenesis, primary neuron imaging, zinc-binding affinity assay |
Nucleic acids research |
High |
32034402
|
| 2022 |
Crystal structure of the SFPQ-NONO heterodimer resolved at 3.0 Å reveals subtle differences in the NOPS region orientation compared to other DBHS dimers, with amino acid substitutions in the NOPS region found mutated in aggressive cancers. |
X-ray crystallography |
Biochimie |
Medium |
35245601
|
| 2018 |
Crystal structure of the SFPQ/PSPC1 heterodimer at 2.3 Å resolution. Analytical ultracentrifugation shows that SFPQ-containing heterodimers have higher affinity than the SFPQ homodimer, and the SFPQ/PSPC1 heterodimer has over 6-fold lower dissociation constant than SFPQ/NONO, suggesting PSPC1 can outcompete NONO for heterodimerization with SFPQ. |
X-ray crystallography, analytical ultracentrifugation |
The Journal of biological chemistry |
High |
29530979
|
| 2019 |
Dido3 interacts with SFPQ via its carboxy terminus and recruits SFPQ to RNA polymerase II for alternative splicing. Loss of Dido3 suppresses SFPQ binding to RNA and increases exon skipping for SFPQ-dependent exons, identifying Dido3 as an adaptor that controls SFPQ utilization in RNA splicing. |
Co-immunoprecipitation, RNA-seq, SFPQ RIP, Dido3 knockout mouse model |
Nucleic acids research |
Medium |
30931476
|
| 2014 |
MALAT1 lncRNA binds to SFPQ, releasing PTBP2 from the SFPQ/PTBP2 complex. The released PTBP2 promotes colorectal cancer cell proliferation and migration, identifying SFPQ as a repressor of PTBP2 function through direct complex formation. |
RNA immunoprecipitation, Co-immunoprecipitation, overexpression/knockdown experiments, in vivo xenograft |
British journal of cancer |
Medium |
25025966
|
| 2006 |
SFPQ, NONO, and PSPC1 interact reciprocally in Sertoli cells and co-localize in androgen receptor complexes. All three DBHS proteins activate androgen receptor-mediated transcription in luciferase reporter assays in Sertoli cell lines. |
Co-immunoprecipitation, luciferase reporter assay, immunofluorescence in mouse testis |
Biology of reproduction |
Medium |
16641145
|
| 2023 |
SFPQ suppresses TGF-β signaling through liquid-liquid phase separation (LLPS) mediated by its prion-like domain (PrLD). SFPQ physically sequesters Smad4 in its condensates, excluding Smad4 from the Smad complex and chromatin, thereby dampening Smad-dependent transcription. SFPQ deficiency or loss of phase separation activity renders cells hypersensitive to TGF-β. |
Co-immunoprecipitation, phase separation assays, ChIP, luciferase reporter, SFPQ knockout/knockdown |
Developmental cell |
High |
38103553
|
| 2022 |
Crystal structure of PSF/SFPQ in complex with a 30-mer RNA at 3.5 Å reveals RNA recognition at two uracil-specific induced-fit binding pockets at domain-swapped inter-subunit RRM1-RRM2 interfaces. Apo structure lacks these pockets, indicating an all-or-nothing conformational transition to high-affinity RNA-binding state with positive cooperativity. |
X-ray crystallography (apo at 2.8 Å and RNA complex at 3.5 Å) |
Biochemistry |
High |
35998361
|
| 2024 |
SFPQ supports EBV latency by maintaining expression of linker histone H1, which occupies latent EBV genomes including the BZLF1 immediate early gene promoter. SFPQ knockout triggers EBV lytic reactivation; enforced H1 expression rescues latency upon SFPQ KO, placing H1 downstream of SFPQ in the latency maintenance pathway. |
CRISPR/Cas9 screen, SFPQ KO, H1 ChIP, rescue by H1 overexpression, RT-PCR for viral gene expression |
Nature communications |
High |
38755141
|
| 2022 |
Two familial ALS-linked SFPQ variants (N533H and L534I) near the zinc-coordinating centre have increased zinc-binding affinities. Crystal structure of SFPQ L534I at 1.83 Å reveals a second zinc-binding site. Overexpression of these mutants increases cytoplasmic SFPQ aggregates in primary neurons and reduces GluA1 (but not GluA2) AMPA receptor surface expression. |
Crystal structure, zinc-binding affinity assay (ITC), primary neuron imaging, surface GluA1/GluA2 quantification |
Open biology |
High |
36168806
|
| 2023 |
The shorter C-terminal low-complexity region (LCR) of SFPQ is the main driver of condensate formation in vitro and in the nucleus. The longer N-terminal prion-like LCR attenuates condensation of the full-length protein, suggesting a regulatory role in preventing aberrant condensate formation. |
In vitro condensation assays, live-cell imaging with LCR deletion constructs, fluorescence recovery after photobleaching |
Journal of molecular biology |
Medium |
37952770
|
| 2025 |
NONO, SFPQ, and PSPC1 associate with catalytically active telomerase through the hTR RNA component. Depletion of DBHS proteins causes telomerase retention in nuclear Cajal bodies and impairs telomerase recruitment to telomeres, resulting in progressive telomere shortening in multiple cell lines. |
Co-immunoprecipitation with hTR, telomerase activity assay, FISH for Cajal body retention, siRNA knockdown, telomere length measurement |
Nature communications |
Medium |
40593584
|
| 2019 |
SFPQ interacts with HDAC1 and co-occupies the CD40 promoter in pulmonary adventitial fibroblasts, suppressing CD40 transcription by switching H3K36me3 to H3K36ac histone modification on the CD40 promoter region. |
ChIP assay, Co-immunoprecipitation, overexpression/knockdown, histone modification analysis |
Cell biology international |
Medium |
31393052
|
| 2024 |
SFPQ depletion affects both primary and mature miRNA expression. SFPQ protects the oncogenic miR-17~92 polycistron from degradation by the nuclear NEXT-exosome complex. BioID on Drosha revealed proximity to SFPQ, and the effect is paraspeckle-independent (NEAT1 depletion does not replicate the SFPQ effect). |
BioID proximity ligation, SFPQ knockdown, transcriptomics, small RNA-seq, miR-17~92 stability assay |
Cell reports |
Medium |
39250314
|
| 2024 |
In Parkinson's disease and dementia with Lewy bodies, NONO and SFPQ form novel nuclear inclusions with adenosine-to-inosine (A-to-I)-edited mRNAs. These NONO/SFPQ aggregates reduce expression of the editing inhibitor ADAR3, increasing A-to-I editing in axonal/synaptic transcripts. Inosine-containing transcripts bind more tightly to recombinant purified SFPQ in vitro and potentiate SFPQ aggregation in human dopamine neurons, creating a self-propagating pathological state. |
Biochemical fractionation of patient brain, in vitro RNA-binding assay with recombinant SFPQ, human iPSC-derived dopamine neurons, immunofluorescence |
Neuron |
High |
38761794
|
| 2021 |
SFPQ overexpression increases numbers of both sense and antisense C9orf72 GGGGCC-repeat RNA foci and dipeptide repeat proteins (DPRs) in transfected cells. Conversely, SFPQ knockdown reduces RNA foci and DPRs in both transfected cells and patient-derived fibroblasts and lymphoblasts from C9orf72 mutation carriers. |
Overexpression/siRNA knockdown, FISH for RNA foci, DPR immunostaining in HEK cells and patient-derived cells |
Journal of cell science |
Medium |
33495278
|
| 2025 |
SFPQ undergoes alternative splicing in ALS to produce an isoform (altSFPQ) lacking a nuclear localization sequence, leading to cytoplasm-predominant localization. altSFPQ has reduced phase separation potential and differential protein binding compared to canonical SFPQ. Increased altSFPQ transcript correlates with decreased canonical SFPQ in familial and sporadic ALS models, providing a mechanistic basis for SFPQ nuclear-to-cytoplasmic redistribution. |
RT-PCR, cellular fractionation, phase separation assays, proteomics, ALS patient/model analysis |
Science advances |
Medium |
40845103
|
| 2024 |
SFPQ interacts with HIV-1 integrase (IN) via two diRGGX1-4 motifs in its N-terminal region. Single amino acid substitutions in either motif reduce IN binding, while mutations in both motifs almost completely disrupt interaction. SFPQ mutants with impaired IN binding fail to enhance viral integration, demonstrating SFPQ promotes HIV-1 integration through direct interaction with integrase. |
Co-immunoprecipitation, site-directed mutagenesis, viral integration assay |
Biochimie |
Medium |
38373651
|
| 2025 |
Structural analysis of SFPQ/NONO heterodimer coiled-coil interactions reveals a flexible coiled-coil interface. Multiple coiled-coil interfaces (not just the canonical one) contribute to SFPQ/NONO tetramerization. A quadruple loss-of-function coiled-coil mutant (QM) abolishes tetramerization; a disulfide-forming variant (R542C) causes constitutive tetramerization, demonstrating the importance of coiled-coil plasticity for polymerization. |
X-ray crystallography, small-angle X-ray scattering with panel of SFPQ/NONO variants |
Nucleic acids research |
High |
39698821
|
| 2016 |
SFPQ associates with LSD1 in the developing cerebral cortex. In vivo shRNA-mediated reduction of SFPQ impairs radial migration of newborn pyramidal neurons and decreases proliferation of progenitor cells, similar to LSD1/CoREST depletion, placing SFPQ in the LSD1/CoREST epigenetic regulatory pathway during cortical development. |
In utero electroporation of shRNA, Co-immunoprecipitation with LSD1, immunohistochemistry, migration assay |
International journal of developmental neuroscience |
Medium |
28034769
|
| 2014 |
JNK1 interacts with SFPQ and NONO in an RNA-dependent manner in neuronal transport granules during NGF-induced differentiation. This interaction is specific (disrupted by JNK substrate-blocking peptide) and occurs in the cytosol. SFPQ knockdown inhibits neurite outgrowth in PC12 cells and acts in the same pathway as JNK. |
SILAC-based quantitative proteomics, co-immunoprecipitation, confocal microscopy, siRNA knockdown, neurite outgrowth assay |
Molecular & cellular proteomics : MCP |
Medium |
25326457
|