{"gene":"SFPQ","run_date":"2026-06-10T07:46:31","timeline":{"discoveries":[{"year":2015,"finding":"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.","method":"X-ray crystallography, small-angle X-ray scattering (SAXS), transmission electron microscopy, site-directed mutagenesis, cellular localization assays","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus SAXS plus mutagenesis with functional cellular readouts, all in one rigorous study","pmids":["25765647"],"is_preprint":false},{"year":2014,"finding":"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.","method":"Chromatin immunoprecipitation, siRNA knockdown, NEAT1 overexpression/induction, immunofluorescence, reporter assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal ChIP, KD experiments with specific phenotypic readout (IL8 expression), mechanism placed in immune pathway","pmids":["24507715"],"is_preprint":false},{"year":2018,"finding":"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.","method":"CLIP-seq, ChIP-seq, mouse conditional knockout, RNA-seq, co-immunoprecipitation","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO mouse model with defined molecular mechanism (CDK9 interaction), multiple orthogonal methods","pmids":["29719248"],"is_preprint":false},{"year":2016,"finding":"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.","method":"RIP, CLIP, fluorescence imaging, siRNA knockdown in neurons, in vivo mouse DRG experiments","journal":"Nature neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (RIP, CLIP, live imaging, KD) with defined axonal viability phenotype","pmids":["27019013"],"is_preprint":false},{"year":2021,"finding":"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.","method":"RNA-seq, SFPQ knockdown, bioinformatic analysis of splicing events across human, mouse, and zebrafish","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — replicated across multiple species with RNA-seq and functional KD, two independent papers (PMID 33476259 and 33771997)","pmids":["33476259","33771997"],"is_preprint":false},{"year":2010,"finding":"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.","method":"Co-immunoprecipitation, siRNA knockdown, sister chromatid cohesion assay, DNA repair assays (comet, γH2AX)","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional HR assays, single lab with multiple orthogonal methods","pmids":["20813759"],"is_preprint":false},{"year":2010,"finding":"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.","method":"Laser microbeam irradiation, live-cell imaging, siRNA knockdown, co-immunoprecipitation, cell cycle analysis","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging of recruitment plus functional repair assays, single lab","pmids":["20421735"],"is_preprint":false},{"year":2017,"finding":"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.","method":"In vitro end-joining assay, shRNA knockdown, radioresistance assay, DNA-PKcs autophosphorylation assay","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstituted in vitro end-joining system with multiple complementary cell-based assays, single lab","pmids":["27924002"],"is_preprint":false},{"year":2015,"finding":"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.","method":"Microwell-based DNA binding/pairing assay, in vitro DNA-PKcs autophosphorylation assay, native SFPQ•NONO purified from HeLa cells","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with purified native complex and multiple biochemical readouts, single lab","pmids":["25998385"],"is_preprint":false},{"year":2015,"finding":"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.","method":"Mass spectrometry of endogenous complex, in vitro methylation assay with PRMT1, mRNP immunoprecipitation","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay plus MS identification plus functional mRNP binding assay, single lab with multiple methods","pmids":["25605962"],"is_preprint":false},{"year":2017,"finding":"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.","method":"Co-immunoprecipitation, in vivo shRNA knockdown in mouse hippocampus, RT-PCR for splice isoforms, behavioral testing","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo mouse KD with rescue experiment plus molecular mechanism (FUS-SFPQ interaction regulating splicing), multiple orthogonal methods","pmids":["28147269"],"is_preprint":false},{"year":2021,"finding":"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.","method":"Co-immunoprecipitation, live imaging of RNA granule transport, genetic mouse model, CMT disease mutations","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, live transport imaging, disease mutation validation, and functional axonal survival assay","pmids":["33284322"],"is_preprint":false},{"year":2017,"finding":"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.","method":"Zebrafish null mutant, rescue with cytoplasmic SFPQ construct, fluorescence imaging, ALS patient-derived variant analysis","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic rescue in a null animal model plus localization-function link, ALS variants confirmed functionally","pmids":["28392072"],"is_preprint":false},{"year":2019,"finding":"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.","method":"ChIP, R-loop detection (DRIP assay), telomere FISH, siRNA knockdown, co-immunoprecipitation","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (ChIP, DRIP, FISH, KD) with mechanistic dissection of heterodimer requirement","pmids":["30824709"],"is_preprint":false},{"year":2020,"finding":"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.","method":"Genetically encoded photocrosslinking, transcriptome-wide m6A profiling, SFPQ overexpression","journal":"Cell chemical biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct crosslinking identifies binding, functional effect on m6A confirmed by transcriptome-wide profiling, single lab","pmids":["31981477"],"is_preprint":false},{"year":2017,"finding":"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.","method":"Quantitative proteomics, HITS-CLIP, transcriptomics, RNA immunoprecipitation, dual-luciferase reporter","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — HITS-CLIP plus proteomics plus functional reporter assays, multiple orthogonal methods in one study","pmids":["29084942"],"is_preprint":false},{"year":2020,"finding":"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.","method":"Co-immunoprecipitation, RNA-IP, siRNA knockdown, alternative splicing analysis","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus RIP plus functional splicing and apoptosis readouts, single lab","pmids":["32332923"],"is_preprint":false},{"year":2011,"finding":"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.","method":"siRNA knockdown, in vitro transcription of recombinant RNPs, virus yield assay, RNA accumulation analysis","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro RNP transcription assay plus multiple siRNA validations with mechanistic dissection of polyadenylation step","pmids":["22114566"],"is_preprint":false},{"year":2010,"finding":"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.","method":"miRNA-mediated PSF knockdown, genetic rescue with PSF mutants, live-cell imaging of laser-induced DNA damage sites","journal":"DNA repair","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging plus mutational dissection, functional rescue assay, single lab","pmids":["21144806"],"is_preprint":false},{"year":2020,"finding":"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.","method":"X-ray crystallography, site-directed mutagenesis, primary neuron imaging, zinc-binding affinity assay","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus mutagenesis plus cellular validation, multiple orthogonal methods in one study","pmids":["32034402"],"is_preprint":false},{"year":2022,"finding":"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.","method":"X-ray crystallography","journal":"Biochimie","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — crystal structure but limited functional follow-up in this study, single lab","pmids":["35245601"],"is_preprint":false},{"year":2018,"finding":"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.","method":"X-ray crystallography, analytical ultracentrifugation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus biophysical dimerization measurements, single lab with two orthogonal methods","pmids":["29530979"],"is_preprint":false},{"year":2019,"finding":"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.","method":"Co-immunoprecipitation, RNA-seq, SFPQ RIP, Dido3 knockout mouse model","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO model plus Co-IP plus RIP, single lab with multiple orthogonal methods","pmids":["30931476"],"is_preprint":false},{"year":2014,"finding":"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.","method":"RNA immunoprecipitation, Co-immunoprecipitation, overexpression/knockdown experiments, in vivo xenograft","journal":"British journal of cancer","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — RIP plus Co-IP in cancer cells, mechanistic model supported but single lab","pmids":["25025966"],"is_preprint":false},{"year":2006,"finding":"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.","method":"Co-immunoprecipitation, luciferase reporter assay, immunofluorescence in mouse testis","journal":"Biology of reproduction","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP plus functional reporter assay, single lab","pmids":["16641145"],"is_preprint":false},{"year":2023,"finding":"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.","method":"Co-immunoprecipitation, phase separation assays, ChIP, luciferase reporter, SFPQ knockout/knockdown","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, ChIP, LLPS assays, reporter, KO), single lab with comprehensive mechanistic dissection","pmids":["38103553"],"is_preprint":false},{"year":2022,"finding":"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.","method":"X-ray crystallography (apo at 2.8 Å and RNA complex at 3.5 Å)","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structures of both apo and RNA-bound forms in one study revealing mechanism of RNA recognition","pmids":["35998361"],"is_preprint":false},{"year":2024,"finding":"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.","method":"CRISPR/Cas9 screen, SFPQ KO, H1 ChIP, rescue by H1 overexpression, RT-PCR for viral gene expression","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-wide screen plus KO validation plus epistatic rescue, multiple orthogonal methods","pmids":["38755141"],"is_preprint":false},{"year":2022,"finding":"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.","method":"Crystal structure, zinc-binding affinity assay (ITC), primary neuron imaging, surface GluA1/GluA2 quantification","journal":"Open biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus biophysical binding assay plus neuronal functional readout, single lab with multiple orthogonal methods","pmids":["36168806"],"is_preprint":false},{"year":2023,"finding":"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.","method":"In vitro condensation assays, live-cell imaging with LCR deletion constructs, fluorescence recovery after photobleaching","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro reconstitution plus cellular imaging, single lab with two complementary methods","pmids":["37952770"],"is_preprint":false},{"year":2025,"finding":"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.","method":"Co-immunoprecipitation with hTR, telomerase activity assay, FISH for Cajal body retention, siRNA knockdown, telomere length measurement","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional localization and telomere length assays, single lab","pmids":["40593584"],"is_preprint":false},{"year":2019,"finding":"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.","method":"ChIP assay, Co-immunoprecipitation, overexpression/knockdown, histone modification analysis","journal":"Cell biology international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus Co-IP plus histone modification analysis, single lab with multiple orthogonal methods","pmids":["31393052"],"is_preprint":false},{"year":2024,"finding":"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).","method":"BioID proximity ligation, SFPQ knockdown, transcriptomics, small RNA-seq, miR-17~92 stability assay","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BioID plus multiple RNA-seq analyses, functional protection from NEXT-exosome identified, single lab","pmids":["39250314"],"is_preprint":false},{"year":2024,"finding":"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.","method":"Biochemical fractionation of patient brain, in vitro RNA-binding assay with recombinant SFPQ, human iPSC-derived dopamine neurons, immunofluorescence","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro binding reconstitution plus patient material plus iPSC-neuron validation, multiple orthogonal methods in one study","pmids":["38761794"],"is_preprint":false},{"year":2021,"finding":"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.","method":"Overexpression/siRNA knockdown, FISH for RNA foci, DPR immunostaining in HEK cells and patient-derived cells","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient-derived cells plus HEK overexpression/KD, replicated in multiple cell types","pmids":["33495278"],"is_preprint":false},{"year":2025,"finding":"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.","method":"RT-PCR, cellular fractionation, phase separation assays, proteomics, ALS patient/model analysis","journal":"Science advances","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple methods in patient samples and models, functional phase separation assay, single lab","pmids":["40845103"],"is_preprint":false},{"year":2024,"finding":"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.","method":"Co-immunoprecipitation, site-directed mutagenesis, viral integration assay","journal":"Biochimie","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis plus functional integration assay, single lab with two orthogonal methods","pmids":["38373651"],"is_preprint":false},{"year":2025,"finding":"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.","method":"X-ray crystallography, small-angle X-ray scattering with panel of SFPQ/NONO variants","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus extensive SAXS panel with mutagenesis, single lab with two orthogonal structural methods","pmids":["39698821"],"is_preprint":false},{"year":2016,"finding":"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.","method":"In utero electroporation of shRNA, Co-immunoprecipitation with LSD1, immunohistochemistry, migration assay","journal":"International journal of developmental neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KD with defined phenotype plus Co-IP placing SFPQ with LSD1, single lab","pmids":["28034769"],"is_preprint":false},{"year":2014,"finding":"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.","method":"SILAC-based quantitative proteomics, co-immunoprecipitation, confocal microscopy, siRNA knockdown, neurite outgrowth assay","journal":"Molecular & cellular proteomics : MCP","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative proteomics plus validated Co-IP plus functional neurite assay, single lab","pmids":["25326457"],"is_preprint":false}],"current_model":"SFPQ is a multifunctional nuclear RNA/DNA-binding protein that forms homo- and heterodimers (with NONO and PSPC1) via a conserved DBHS domain, and polymerizes through an anti-parallel coiled-coil into linear assemblies that template paraspeckle nuclear bodies; it regulates transcription (acting as a promoter-bound repressor or activator, sequestering Smad4 via LLPS to suppress TGF-β signaling, and supporting transcriptional elongation of long genes by mediating CDK9 recruitment to the elongation complex), pre-mRNA splicing (including suppression of cryptic last exons and regulation of tau exon 10 alternative splicing in complex with FUS), axonal RNA granule transport via KIF5A/KLC1 motors, DNA double-strand break repair via canonical NHEJ (by DNA pairing/synapsis independent of free ends), homologous recombination (through direct interaction with RAD51D), and telomerase recruitment to telomeres; its activity is modulated by PRMT1-mediated arginine methylation (enhancing mRNA binding), zinc-induced polymerization (driving cytoplasmic mislocalization linked to neurodegeneration), and alternative splicing to produce a cytoplasmic isoform lacking a nuclear localization sequence that is upregulated in ALS."},"narrative":{"mechanistic_narrative":"SFPQ is a multifunctional nuclear DBHS protein that builds higher-order assemblies through an anti-parallel coiled-coil to template nuclear bodies and coordinate transcription, RNA processing, and genome maintenance [PMID:25765647, PMID:39698821]. It dimerizes with itself and with related DBHS proteins NONO and PSPC1, with SFPQ/PSPC1 binding more tightly than SFPQ/NONO, establishing competitive partner selection within the family [PMID:29530979], and reaches a high-affinity, cooperative RNA-binding state through an induced-fit conformational switch at its domain-swapped RRM1-RRM2 interfaces [PMID:35998361]. As a transcriptional regulator it acts both as a promoter-bound repressor that relocates to paraspeckles upon NEAT1 induction to de-repress IL8 during innate immune responses [PMID:24507715], and as an elongation factor that binds long introns and recruits CDK9 to sustain expression of long neuronal genes [PMID:29719248]; it also suppresses TGF-β signaling by sequestering Smad4 in prion-like-domain-driven condensates [PMID:38103553]. In RNA metabolism SFPQ enforces accurate splicing of long introns, suppresses cryptic last exons and premature polyadenylation [PMID:33476259, PMID:33771997], and partners with FUS to control Mapt exon 10 splicing and the 4R/3R-tau ratio [PMID:28147269]. SFPQ assembles target mRNAs into axonal transport granules carried by the KIF5A/KLC1 kinesin motor, a function essential for axon survival [PMID:27019013, PMID:33284322]. In genome maintenance the SFPQ•NONO complex binds internal DNA, drives end-independent synapsis and DNA-PKcs autophosphorylation to promote canonical NHEJ [PMID:27924002, PMID:25998385], supports homologous recombination via RAD51D [PMID:20813759], and suppresses telomeric R-loops while recruiting telomerase through hTR [PMID:30824709, PMID:40593584]. SFPQ activity is tuned by PRMT1-mediated arginine methylation that enhances mRNA binding [PMID:25605962] and by zinc-induced polymerization that drives cytoplasmic aggregation [PMID:32034402]. Aberrant cytoplasmic redistribution—through ALS-linked coiled-coil and zinc-center variants, an NLS-lacking alternatively spliced isoform, and self-propagating inclusions in Parkinson's disease—links SFPQ dysfunction to neurodegeneration [PMID:28392072, PMID:36168806, PMID:38761794, PMID:40845103].","teleology":[{"year":2006,"claim":"Established that SFPQ acts together with the other DBHS proteins NONO and PSPC1 as a transcriptional coactivator, framing the family as cooperative partners rather than independent factors.","evidence":"Co-IP, luciferase reporters, and immunofluorescence in Sertoli cells showing reciprocal interaction and androgen receptor coactivation","pmids":["16641145"],"confidence":"Medium","gaps":["No structural basis for heterodimer choice","Whether coactivation generalizes beyond androgen receptor unaddressed"]},{"year":2010,"claim":"Defined SFPQ as an active player in DNA double-strand break repair, distinguishing a direct HR role via RAD51D from rapid SFPQ/NONO recruitment to break sites.","evidence":"Co-IP with RAD51D, laser microirradiation recruitment imaging, HR/cohesion assays, and synthetic lethality testing in human cells","pmids":["20813759","20421735","21144806"],"confidence":"Medium","gaps":["Mechanism distinguishing HR versus NHEJ contributions unresolved","N-terminal domain requirement for relocalization mechanistically undefined"]},{"year":2014,"claim":"Connected SFPQ promoter occupancy to lncRNA-controlled gene regulation, showing NEAT1-driven paraspeckle relocalization de-represses target genes in immunity, and identified competing RNA/protein partnerships (MALAT1, PTBP2).","evidence":"ChIP, NEAT1 induction, knockdown with IL8 readout, plus RIP/Co-IP characterizing MALAT1-SFPQ-PTBP2 in cancer cells","pmids":["24507715","25025966"],"confidence":"High","gaps":["Generality of relocalization-based de-repression across promoters unknown","PTBP2 release mechanism is single-lab"]},{"year":2015,"claim":"Provided the structural and biochemical foundation: SFPQ polymerizes via an anti-parallel coiled-coil essential for cellular function, and the SFPQ•NONO complex performs end-independent DNA synapsis in NHEJ.","evidence":"Crystal structure, SAXS, EM, and mutagenesis with cellular readouts; in vitro DNA pairing and DNA-PKcs autophosphorylation assays with native complex","pmids":["25765647","25998385"],"confidence":"High","gaps":["In vivo regulation of polymerization length not established","How synapsis activity integrates with canonical NHEJ machinery in cells partly open"]},{"year":2015,"claim":"Identified post-translational control of SFPQ RNA binding, showing PRMT1 arginine methylation enhances mRNA association and citrullination antagonizes it.","evidence":"Mass spectrometry of endogenous complex, in vitro PRMT1 methylation, and mRNP immunoprecipitation","pmids":["25605962"],"confidence":"High","gaps":["Signals controlling methylation state in vivo unknown","Functional consequences for specific transcripts not mapped"]},{"year":2016,"claim":"Defined SFPQ as an RNA-granule organizer and elongation factor required for neuronal gene programs, linking it to axonal mRNA transport and cortical development.","evidence":"RIP/CLIP and axonal imaging in DRG neurons; CLIP-seq/ChIP-seq with conditional KO mouse for CDK9-dependent elongation; LSD1 Co-IP with in utero electroporation","pmids":["27019013","29719248","28034769"],"confidence":"High","gaps":["How nuclear elongation and cytoplasmic transport functions are coordinated unclear","LSD1 pathway role is correlative"]},{"year":2017,"claim":"Established SFPQ's splicing function in disease-relevant contexts and confirmed a cytoplasmic requirement, showing FUS-SFPQ controls tau isoform ratio and that axonal SFPQ is functionally essential.","evidence":"In vivo hippocampal shRNA with rescue and behavior; zebrafish null rescue with cytoplasmic-only SFPQ and ALS variant analysis; Ago2 HITS-CLIP for nucleoplasmic miRNA targeting","pmids":["28147269","28392072","29084942"],"confidence":"High","gaps":["Molecular basis of cytoplasmic SFPQ partner switching not resolved","Link between splicing and miRNA functions undefined"]},{"year":2017,"claim":"Reconstituted SFPQ•NONO substituting for XLF in canonical NHEJ in vitro while showing partly distinct cellular roles.","evidence":"In vitro end-joining, shRNA, radioresistance, and DNA-PKcs autophosphorylation assays","pmids":["27924002"],"confidence":"High","gaps":["Relative in vivo contribution versus XLF not quantified","Single-lab reconstitution"]},{"year":2018,"claim":"Refined DBHS partner selection and identified an adaptor for SFPQ splicing utilization, showing SFPQ/PSPC1 outcompetes SFPQ/NONO and Dido3 recruits SFPQ to Pol II.","evidence":"Crystal structures with analytical ultracentrifugation; Dido3 KO mouse with Co-IP and RIP","pmids":["29530979","30931476"],"confidence":"Medium","gaps":["Cellular determinants of which heterodimer forms not established","Whether Dido3 governs all SFPQ-dependent exons unknown"]},{"year":2019,"claim":"Extended genome-maintenance roles to telomeres and chromatin, showing SFPQ/NONO suppress telomeric R-loops and SFPQ-HDAC1 represses CD40 via histone modification switching.","evidence":"ChIP, DRIP, telomere FISH, knockdown for telomeres; ChIP/Co-IP and histone modification analysis for CD40","pmids":["30824709","31393052"],"confidence":"Medium","gaps":["Mechanism coupling R-loop suppression to HR restraint partial","CD40 H3K36 switch is single-lab"]},{"year":2020,"claim":"Linked metal-driven polymerization to cytoplasmic aggregation and added m6A and cancer-splicing regulatory roles, mechanistically tying SFPQ biophysics to neurodegeneration.","evidence":"Zinc-bound crystal structure with neuron imaging; FTO photocrosslinking with m6A profiling; SFPQ/NONO-SRSF2 Co-IP/RIP in platinum-resistant ovarian cancer","pmids":["32034402","31981477","32332923"],"confidence":"High","gaps":["Physiological zinc levels triggering aggregation in vivo unknown","FTO recruitment specificity determinants undefined"]},{"year":2021,"claim":"Identified the kinesin motor for axonal SFPQ-RNA granule transport and connected SFPQ to C9orf72 repeat RNA biology, broadening its neurodegeneration links.","evidence":"Reciprocal Co-IP, live transport imaging, mouse model, and CMT KIF5A mutation analysis; FISH/DPR quantification with overexpression and patient-derived cells","pmids":["33284322","33495278"],"confidence":"High","gaps":["How motor cargo loading is regulated unknown","Mechanism by which SFPQ promotes repeat RNA foci not defined"]},{"year":2022,"claim":"Resolved the structural mechanism of cooperative RNA recognition and the SFPQ-NONO heterodimer architecture, mapping cancer mutations to the NOPS interface.","evidence":"Crystal structures of apo and RNA-bound SFPQ and of the SFPQ-NONO heterodimer","pmids":["35998361","35245601"],"confidence":"High","gaps":["Functional consequence of NOPS-region cancer mutations untested","Cooperativity in the cellular context not validated"]},{"year":2022,"claim":"Connected familial ALS variants to enhanced zinc binding and a synaptic deficit, providing a structural mechanism for SFPQ aggregation in disease.","evidence":"Crystal structure of L534I, ITC zinc-binding affinity, primary neuron imaging, and GluA1/GluA2 surface quantification","pmids":["36168806"],"confidence":"High","gaps":["In vivo pathogenicity of variants not demonstrated","Link from aggregation to GluA1 reduction mechanistically incomplete"]},{"year":2023,"claim":"Established phase separation as a regulatory mode, showing SFPQ condensates sequester Smad4 to suppress TGF-β and that the two low-complexity regions oppositely tune condensation.","evidence":"LLPS assays, Co-IP, ChIP, reporter, and KO for Smad4 sequestration; in vitro condensation and FRAP with LCR-deletion constructs","pmids":["38103553","37952770"],"confidence":"High","gaps":["How condensate formation is triggered by upstream signals unclear","Relationship between Smad4 sequestration and paraspeckle condensates undefined"]},{"year":2024,"claim":"Expanded SFPQ into miRNA stability, viral life cycles, and a self-propagating neurodegenerative inclusion mechanism, diversifying its RNA-protective and pathological roles.","evidence":"BioID/small RNA-seq for miR-17~92 protection; CRISPR screen/KO and H1 ChIP for EBV latency; Co-IP/integration assay for HIV-1 integrase; patient brain fractionation and iPSC dopamine neurons for A-to-I-edited RNA inclusions","pmids":["39250314","38755141","38373651","38761794"],"confidence":"High","gaps":["Whether viral and miRNA roles share a common biochemical basis unknown","Trigger initiating PD inclusion seeding undefined"]},{"year":2025,"claim":"Refined polymerization mechanics, telomerase recruitment, and the ALS redistribution mechanism, showing coiled-coil plasticity drives tetramerization and an NLS-lacking isoform underlies cytoplasmic SFPQ.","evidence":"Crystallography/SAXS of SFPQ/NONO coiled-coil variants; hTR Co-IP with telomere length assays; RT-PCR/fractionation/proteomics of altSFPQ in ALS models","pmids":["39698821","40593584","40845103"],"confidence":"Medium","gaps":["Regulation of altSFPQ splicing choice unknown","Telomerase recruitment role is single-lab and Co-IP-based"]},{"year":null,"claim":"How SFPQ's many functions are partitioned—which heterodimer, modification state, and condensate context dictate transcription versus splicing versus DNA repair versus axonal transport in a given cell—remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking partner choice to functional output","Physiological switches between nuclear and cytoplasmic SFPQ pools undefined","Causal contribution of SFPQ mislocalization to human disease in vivo not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[3,9,15,26]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,8]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,2,25,31]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[22,11]},{"term_id":"GO:0140313","term_label":"molecular sequestering activity","supporting_discovery_ids":[25]}],"localization":[{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[0,1,15]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[3,12,35,39]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,2,25]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,2,25]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[4,15,32]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[5,7,8]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[25]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[3,11]}],"complexes":["SFPQ/NONO heterodimer","SFPQ/PSPC1 heterodimer","paraspeckle","SFPQ-KIF5A/KLC1 transport complex"],"partners":["NONO","PSPC1","RAD51D","FUS","CDK9","KIF5A","SMAD4","FTO"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P23246","full_name":"Splicing factor, proline- and glutamine-rich","aliases":["100 kDa DNA-pairing protein","hPOMp100","DNA-binding p52/p100 complex, 100 kDa subunit","Polypyrimidine tract-binding protein-associated-splicing factor","PSF","PTB-associated-splicing factor"],"length_aa":707,"mass_kda":76.1,"function":"DNA- and RNA binding protein, involved in several nuclear processes. Essential pre-mRNA splicing factor required early in spliceosome formation and for splicing catalytic step II, probably as a heteromer with NONO. Binds to pre-mRNA in spliceosome C complex, and specifically binds to intronic polypyrimidine tracts. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45, a phosphorylated form is sequestered by THRAP3 from the pre-mRNA in resting T-cells; T-cell activation and subsequent reduced phosphorylation is proposed to lead to release from THRAP3 allowing binding to pre-mRNA splicing regulatotry elements which represses exon inclusion. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and polyadenylation process as component of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. SFPQ may be involved in homologous DNA pairing; in vitro, promotes the invasion of ssDNA between a duplex DNA and produces a D-loop formation. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1; in vitro, stimulates dissociation of TOP1 from DNA after cleavage and enhances its jumping between separate DNA helices. The SFPQ-NONO heteromer binds DNA (PubMed:25765647). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends; in vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. SFPQ is involved in transcriptional regulation. Functions as a transcriptional activator (PubMed:25765647). Transcriptional repression is mediated by an interaction of SFPQ with SIN3A and subsequent recruitment of histone deacetylases (HDACs). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. SFPQ isoform Long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA and probably THRA, and acts as a transcriptional corepressor in absence of hormone ligands. Binds the DNA sequence 5'-CTGAGTC-3' in the insulin-like growth factor response element (IGFRE) and inhibits IGF1-stimulated transcriptional activity. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation (By similarity). Required for the assembly of nuclear speckles (PubMed:25765647). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728)","subcellular_location":"Nucleus speckle; Nucleus matrix; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P23246/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SFPQ","classification":"Common 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RNF43","url":"https://www.omim.org/entry/612482"},{"mim_id":"612408","title":"PARASPECKLE COMPONENT 1; PSPC1","url":"https://www.omim.org/entry/612408"},{"mim_id":"605199","title":"SPLICING FACTOR, PROLINE- AND GLUTAMINE-RICH; SFPQ","url":"https://www.omim.org/entry/605199"},{"mim_id":"602533","title":"ONCOGENE DJ1; DJ1","url":"https://www.omim.org/entry/602533"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SFPQ"},"hgnc":{"alias_symbol":["PSF","PPP1R140"],"prev_symbol":[]},"alphafold":{"accession":"P23246","domains":[{"cath_id":"3.30.70.330","chopping":"287-368","consensus_level":"medium","plddt":91.3827,"start":287,"end":368},{"cath_id":"3.30.70.330","chopping":"371-451","consensus_level":"medium","plddt":96.7357,"start":371,"end":451}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P23246","model_url":"https://alphafold.ebi.ac.uk/files/AF-P23246-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P23246-F1-predicted_aligned_error_v6.png","plddt_mean":67.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SFPQ","jax_strain_url":"https://www.jax.org/strain/search?query=SFPQ"},"sequence":{"accession":"P23246","fasta_url":"https://rest.uniprot.org/uniprotkb/P23246.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P23246/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P23246"}},"corpus_meta":[{"pmid":"24507715","id":"PMC_24507715","title":"Long 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\"finding\": \"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.\",\n      \"method\": \"X-ray crystallography, small-angle X-ray scattering (SAXS), transmission electron microscopy, site-directed mutagenesis, cellular localization assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus SAXS plus mutagenesis with functional cellular readouts, all in one rigorous study\",\n      \"pmids\": [\"25765647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"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.\",\n      \"method\": \"Chromatin immunoprecipitation, siRNA knockdown, NEAT1 overexpression/induction, immunofluorescence, reporter assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal ChIP, KD experiments with specific phenotypic readout (IL8 expression), mechanism placed in immune pathway\",\n      \"pmids\": [\"24507715\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"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.\",\n      \"method\": \"CLIP-seq, ChIP-seq, mouse conditional knockout, RNA-seq, co-immunoprecipitation\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO mouse model with defined molecular mechanism (CDK9 interaction), multiple orthogonal methods\",\n      \"pmids\": [\"29719248\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"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.\",\n      \"method\": \"RIP, CLIP, fluorescence imaging, siRNA knockdown in neurons, in vivo mouse DRG experiments\",\n      \"journal\": \"Nature neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (RIP, CLIP, live imaging, KD) with defined axonal viability phenotype\",\n      \"pmids\": [\"27019013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"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.\",\n      \"method\": \"RNA-seq, SFPQ knockdown, bioinformatic analysis of splicing events across human, mouse, and zebrafish\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — replicated across multiple species with RNA-seq and functional KD, two independent papers (PMID 33476259 and 33771997)\",\n      \"pmids\": [\"33476259\", \"33771997\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, sister chromatid cohesion assay, DNA repair assays (comet, γH2AX)\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional HR assays, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"20813759\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"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.\",\n      \"method\": \"Laser microbeam irradiation, live-cell imaging, siRNA knockdown, co-immunoprecipitation, cell cycle analysis\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging of recruitment plus functional repair assays, single lab\",\n      \"pmids\": [\"20421735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"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.\",\n      \"method\": \"In vitro end-joining assay, shRNA knockdown, radioresistance assay, DNA-PKcs autophosphorylation assay\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstituted in vitro end-joining system with multiple complementary cell-based assays, single lab\",\n      \"pmids\": [\"27924002\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"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.\",\n      \"method\": \"Microwell-based DNA binding/pairing assay, in vitro DNA-PKcs autophosphorylation assay, native SFPQ•NONO purified from HeLa cells\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with purified native complex and multiple biochemical readouts, single lab\",\n      \"pmids\": [\"25998385\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"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.\",\n      \"method\": \"Mass spectrometry of endogenous complex, in vitro methylation assay with PRMT1, mRNP immunoprecipitation\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay plus MS identification plus functional mRNP binding assay, single lab with multiple methods\",\n      \"pmids\": [\"25605962\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, in vivo shRNA knockdown in mouse hippocampus, RT-PCR for splice isoforms, behavioral testing\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo mouse KD with rescue experiment plus molecular mechanism (FUS-SFPQ interaction regulating splicing), multiple orthogonal methods\",\n      \"pmids\": [\"28147269\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, live imaging of RNA granule transport, genetic mouse model, CMT disease mutations\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, live transport imaging, disease mutation validation, and functional axonal survival assay\",\n      \"pmids\": [\"33284322\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"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.\",\n      \"method\": \"Zebrafish null mutant, rescue with cytoplasmic SFPQ construct, fluorescence imaging, ALS patient-derived variant analysis\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic rescue in a null animal model plus localization-function link, ALS variants confirmed functionally\",\n      \"pmids\": [\"28392072\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"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.\",\n      \"method\": \"ChIP, R-loop detection (DRIP assay), telomere FISH, siRNA knockdown, co-immunoprecipitation\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (ChIP, DRIP, FISH, KD) with mechanistic dissection of heterodimer requirement\",\n      \"pmids\": [\"30824709\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"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.\",\n      \"method\": \"Genetically encoded photocrosslinking, transcriptome-wide m6A profiling, SFPQ overexpression\",\n      \"journal\": \"Cell chemical biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct crosslinking identifies binding, functional effect on m6A confirmed by transcriptome-wide profiling, single lab\",\n      \"pmids\": [\"31981477\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"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.\",\n      \"method\": \"Quantitative proteomics, HITS-CLIP, transcriptomics, RNA immunoprecipitation, dual-luciferase reporter\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — HITS-CLIP plus proteomics plus functional reporter assays, multiple orthogonal methods in one study\",\n      \"pmids\": [\"29084942\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, RNA-IP, siRNA knockdown, alternative splicing analysis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus RIP plus functional splicing and apoptosis readouts, single lab\",\n      \"pmids\": [\"32332923\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"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.\",\n      \"method\": \"siRNA knockdown, in vitro transcription of recombinant RNPs, virus yield assay, RNA accumulation analysis\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro RNP transcription assay plus multiple siRNA validations with mechanistic dissection of polyadenylation step\",\n      \"pmids\": [\"22114566\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"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.\",\n      \"method\": \"miRNA-mediated PSF knockdown, genetic rescue with PSF mutants, live-cell imaging of laser-induced DNA damage sites\",\n      \"journal\": \"DNA repair\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging plus mutational dissection, functional rescue assay, single lab\",\n      \"pmids\": [\"21144806\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"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.\",\n      \"method\": \"X-ray crystallography, site-directed mutagenesis, primary neuron imaging, zinc-binding affinity assay\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus mutagenesis plus cellular validation, multiple orthogonal methods in one study\",\n      \"pmids\": [\"32034402\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"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.\",\n      \"method\": \"X-ray crystallography\",\n      \"journal\": \"Biochimie\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystal structure but limited functional follow-up in this study, single lab\",\n      \"pmids\": [\"35245601\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"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.\",\n      \"method\": \"X-ray crystallography, analytical ultracentrifugation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus biophysical dimerization measurements, single lab with two orthogonal methods\",\n      \"pmids\": [\"29530979\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, RNA-seq, SFPQ RIP, Dido3 knockout mouse model\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO model plus Co-IP plus RIP, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"30931476\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"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.\",\n      \"method\": \"RNA immunoprecipitation, Co-immunoprecipitation, overexpression/knockdown experiments, in vivo xenograft\",\n      \"journal\": \"British journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — RIP plus Co-IP in cancer cells, mechanistic model supported but single lab\",\n      \"pmids\": [\"25025966\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, luciferase reporter assay, immunofluorescence in mouse testis\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP plus functional reporter assay, single lab\",\n      \"pmids\": [\"16641145\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, phase separation assays, ChIP, luciferase reporter, SFPQ knockout/knockdown\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, ChIP, LLPS assays, reporter, KO), single lab with comprehensive mechanistic dissection\",\n      \"pmids\": [\"38103553\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"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.\",\n      \"method\": \"X-ray crystallography (apo at 2.8 Å and RNA complex at 3.5 Å)\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structures of both apo and RNA-bound forms in one study revealing mechanism of RNA recognition\",\n      \"pmids\": [\"35998361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"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.\",\n      \"method\": \"CRISPR/Cas9 screen, SFPQ KO, H1 ChIP, rescue by H1 overexpression, RT-PCR for viral gene expression\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-wide screen plus KO validation plus epistatic rescue, multiple orthogonal methods\",\n      \"pmids\": [\"38755141\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"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.\",\n      \"method\": \"Crystal structure, zinc-binding affinity assay (ITC), primary neuron imaging, surface GluA1/GluA2 quantification\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus biophysical binding assay plus neuronal functional readout, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"36168806\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"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.\",\n      \"method\": \"In vitro condensation assays, live-cell imaging with LCR deletion constructs, fluorescence recovery after photobleaching\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro reconstitution plus cellular imaging, single lab with two complementary methods\",\n      \"pmids\": [\"37952770\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation with hTR, telomerase activity assay, FISH for Cajal body retention, siRNA knockdown, telomere length measurement\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional localization and telomere length assays, single lab\",\n      \"pmids\": [\"40593584\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"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.\",\n      \"method\": \"ChIP assay, Co-immunoprecipitation, overexpression/knockdown, histone modification analysis\",\n      \"journal\": \"Cell biology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus Co-IP plus histone modification analysis, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"31393052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"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).\",\n      \"method\": \"BioID proximity ligation, SFPQ knockdown, transcriptomics, small RNA-seq, miR-17~92 stability assay\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BioID plus multiple RNA-seq analyses, functional protection from NEXT-exosome identified, single lab\",\n      \"pmids\": [\"39250314\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"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.\",\n      \"method\": \"Biochemical fractionation of patient brain, in vitro RNA-binding assay with recombinant SFPQ, human iPSC-derived dopamine neurons, immunofluorescence\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro binding reconstitution plus patient material plus iPSC-neuron validation, multiple orthogonal methods in one study\",\n      \"pmids\": [\"38761794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"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.\",\n      \"method\": \"Overexpression/siRNA knockdown, FISH for RNA foci, DPR immunostaining in HEK cells and patient-derived cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient-derived cells plus HEK overexpression/KD, replicated in multiple cell types\",\n      \"pmids\": [\"33495278\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"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.\",\n      \"method\": \"RT-PCR, cellular fractionation, phase separation assays, proteomics, ALS patient/model analysis\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple methods in patient samples and models, functional phase separation assay, single lab\",\n      \"pmids\": [\"40845103\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, site-directed mutagenesis, viral integration assay\",\n      \"journal\": \"Biochimie\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis plus functional integration assay, single lab with two orthogonal methods\",\n      \"pmids\": [\"38373651\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"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.\",\n      \"method\": \"X-ray crystallography, small-angle X-ray scattering with panel of SFPQ/NONO variants\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus extensive SAXS panel with mutagenesis, single lab with two orthogonal structural methods\",\n      \"pmids\": [\"39698821\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"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.\",\n      \"method\": \"In utero electroporation of shRNA, Co-immunoprecipitation with LSD1, immunohistochemistry, migration assay\",\n      \"journal\": \"International journal of developmental neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KD with defined phenotype plus Co-IP placing SFPQ with LSD1, single lab\",\n      \"pmids\": [\"28034769\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"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.\",\n      \"method\": \"SILAC-based quantitative proteomics, co-immunoprecipitation, confocal microscopy, siRNA knockdown, neurite outgrowth assay\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative proteomics plus validated Co-IP plus functional neurite assay, single lab\",\n      \"pmids\": [\"25326457\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SFPQ is a multifunctional nuclear RNA/DNA-binding protein that forms homo- and heterodimers (with NONO and PSPC1) via a conserved DBHS domain, and polymerizes through an anti-parallel coiled-coil into linear assemblies that template paraspeckle nuclear bodies; it regulates transcription (acting as a promoter-bound repressor or activator, sequestering Smad4 via LLPS to suppress TGF-β signaling, and supporting transcriptional elongation of long genes by mediating CDK9 recruitment to the elongation complex), pre-mRNA splicing (including suppression of cryptic last exons and regulation of tau exon 10 alternative splicing in complex with FUS), axonal RNA granule transport via KIF5A/KLC1 motors, DNA double-strand break repair via canonical NHEJ (by DNA pairing/synapsis independent of free ends), homologous recombination (through direct interaction with RAD51D), and telomerase recruitment to telomeres; its activity is modulated by PRMT1-mediated arginine methylation (enhancing mRNA binding), zinc-induced polymerization (driving cytoplasmic mislocalization linked to neurodegeneration), and alternative splicing to produce a cytoplasmic isoform lacking a nuclear localization sequence that is upregulated in ALS.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SFPQ is a multifunctional nuclear DBHS protein that builds higher-order assemblies through an anti-parallel coiled-coil to template nuclear bodies and coordinate transcription, RNA processing, and genome maintenance [#0, #37]. It dimerizes with itself and with related DBHS proteins NONO and PSPC1, with SFPQ/PSPC1 binding more tightly than SFPQ/NONO, establishing competitive partner selection within the family [#21], and reaches a high-affinity, cooperative RNA-binding state through an induced-fit conformational switch at its domain-swapped RRM1-RRM2 interfaces [#26]. As a transcriptional regulator it acts both as a promoter-bound repressor that relocates to paraspeckles upon NEAT1 induction to de-repress IL8 during innate immune responses [#1], and as an elongation factor that binds long introns and recruits CDK9 to sustain expression of long neuronal genes [#2]; it also suppresses TGF-\\u03b2 signaling by sequestering Smad4 in prion-like-domain-driven condensates [#25]. In RNA metabolism SFPQ enforces accurate splicing of long introns, suppresses cryptic last exons and premature polyadenylation [#4], and partners with FUS to control Mapt exon 10 splicing and the 4R/3R-tau ratio [#10]. SFPQ assembles target mRNAs into axonal transport granules carried by the KIF5A/KLC1 kinesin motor, a function essential for axon survival [#3, #11]. In genome maintenance the SFPQ\\u2022NONO complex binds internal DNA, drives end-independent synapsis and DNA-PKcs autophosphorylation to promote canonical NHEJ [#7, #8], supports homologous recombination via RAD51D [#5], and suppresses telomeric R-loops while recruiting telomerase through hTR [#13, #30]. SFPQ activity is tuned by PRMT1-mediated arginine methylation that enhances mRNA binding [#9] and by zinc-induced polymerization that drives cytoplasmic aggregation [#19]. Aberrant cytoplasmic redistribution\\u2014through ALS-linked coiled-coil and zinc-center variants, an NLS-lacking alternatively spliced isoform, and self-propagating inclusions in Parkinson's disease\\u2014links SFPQ dysfunction to neurodegeneration [#12, #28, #33, #35].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established that SFPQ acts together with the other DBHS proteins NONO and PSPC1 as a transcriptional coactivator, framing the family as cooperative partners rather than independent factors.\",\n      \"evidence\": \"Co-IP, luciferase reporters, and immunofluorescence in Sertoli cells showing reciprocal interaction and androgen receptor coactivation\",\n      \"pmids\": [\"16641145\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural basis for heterodimer choice\", \"Whether coactivation generalizes beyond androgen receptor unaddressed\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Defined SFPQ as an active player in DNA double-strand break repair, distinguishing a direct HR role via RAD51D from rapid SFPQ/NONO recruitment to break sites.\",\n      \"evidence\": \"Co-IP with RAD51D, laser microirradiation recruitment imaging, HR/cohesion assays, and synthetic lethality testing in human cells\",\n      \"pmids\": [\"20813759\", \"20421735\", \"21144806\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism distinguishing HR versus NHEJ contributions unresolved\", \"N-terminal domain requirement for relocalization mechanistically undefined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected SFPQ promoter occupancy to lncRNA-controlled gene regulation, showing NEAT1-driven paraspeckle relocalization de-represses target genes in immunity, and identified competing RNA/protein partnerships (MALAT1, PTBP2).\",\n      \"evidence\": \"ChIP, NEAT1 induction, knockdown with IL8 readout, plus RIP/Co-IP characterizing MALAT1-SFPQ-PTBP2 in cancer cells\",\n      \"pmids\": [\"24507715\", \"25025966\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generality of relocalization-based de-repression across promoters unknown\", \"PTBP2 release mechanism is single-lab\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Provided the structural and biochemical foundation: SFPQ polymerizes via an anti-parallel coiled-coil essential for cellular function, and the SFPQ\\u2022NONO complex performs end-independent DNA synapsis in NHEJ.\",\n      \"evidence\": \"Crystal structure, SAXS, EM, and mutagenesis with cellular readouts; in vitro DNA pairing and DNA-PKcs autophosphorylation assays with native complex\",\n      \"pmids\": [\"25765647\", \"25998385\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo regulation of polymerization length not established\", \"How synapsis activity integrates with canonical NHEJ machinery in cells partly open\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identified post-translational control of SFPQ RNA binding, showing PRMT1 arginine methylation enhances mRNA association and citrullination antagonizes it.\",\n      \"evidence\": \"Mass spectrometry of endogenous complex, in vitro PRMT1 methylation, and mRNP immunoprecipitation\",\n      \"pmids\": [\"25605962\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Signals controlling methylation state in vivo unknown\", \"Functional consequences for specific transcripts not mapped\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defined SFPQ as an RNA-granule organizer and elongation factor required for neuronal gene programs, linking it to axonal mRNA transport and cortical development.\",\n      \"evidence\": \"RIP/CLIP and axonal imaging in DRG neurons; CLIP-seq/ChIP-seq with conditional KO mouse for CDK9-dependent elongation; LSD1 Co-IP with in utero electroporation\",\n      \"pmids\": [\"27019013\", \"29719248\", \"28034769\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How nuclear elongation and cytoplasmic transport functions are coordinated unclear\", \"LSD1 pathway role is correlative\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Established SFPQ's splicing function in disease-relevant contexts and confirmed a cytoplasmic requirement, showing FUS-SFPQ controls tau isoform ratio and that axonal SFPQ is functionally essential.\",\n      \"evidence\": \"In vivo hippocampal shRNA with rescue and behavior; zebrafish null rescue with cytoplasmic-only SFPQ and ALS variant analysis; Ago2 HITS-CLIP for nucleoplasmic miRNA targeting\",\n      \"pmids\": [\"28147269\", \"28392072\", \"29084942\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of cytoplasmic SFPQ partner switching not resolved\", \"Link between splicing and miRNA functions undefined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Reconstituted SFPQ\\u2022NONO substituting for XLF in canonical NHEJ in vitro while showing partly distinct cellular roles.\",\n      \"evidence\": \"In vitro end-joining, shRNA, radioresistance, and DNA-PKcs autophosphorylation assays\",\n      \"pmids\": [\"27924002\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative in vivo contribution versus XLF not quantified\", \"Single-lab reconstitution\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Refined DBHS partner selection and identified an adaptor for SFPQ splicing utilization, showing SFPQ/PSPC1 outcompetes SFPQ/NONO and Dido3 recruits SFPQ to Pol II.\",\n      \"evidence\": \"Crystal structures with analytical ultracentrifugation; Dido3 KO mouse with Co-IP and RIP\",\n      \"pmids\": [\"29530979\", \"30931476\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cellular determinants of which heterodimer forms not established\", \"Whether Dido3 governs all SFPQ-dependent exons unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extended genome-maintenance roles to telomeres and chromatin, showing SFPQ/NONO suppress telomeric R-loops and SFPQ-HDAC1 represses CD40 via histone modification switching.\",\n      \"evidence\": \"ChIP, DRIP, telomere FISH, knockdown for telomeres; ChIP/Co-IP and histone modification analysis for CD40\",\n      \"pmids\": [\"30824709\", \"31393052\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism coupling R-loop suppression to HR restraint partial\", \"CD40 H3K36 switch is single-lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linked metal-driven polymerization to cytoplasmic aggregation and added m6A and cancer-splicing regulatory roles, mechanistically tying SFPQ biophysics to neurodegeneration.\",\n      \"evidence\": \"Zinc-bound crystal structure with neuron imaging; FTO photocrosslinking with m6A profiling; SFPQ/NONO-SRSF2 Co-IP/RIP in platinum-resistant ovarian cancer\",\n      \"pmids\": [\"32034402\", \"31981477\", \"32332923\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological zinc levels triggering aggregation in vivo unknown\", \"FTO recruitment specificity determinants undefined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified the kinesin motor for axonal SFPQ-RNA granule transport and connected SFPQ to C9orf72 repeat RNA biology, broadening its neurodegeneration links.\",\n      \"evidence\": \"Reciprocal Co-IP, live transport imaging, mouse model, and CMT KIF5A mutation analysis; FISH/DPR quantification with overexpression and patient-derived cells\",\n      \"pmids\": [\"33284322\", \"33495278\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How motor cargo loading is regulated unknown\", \"Mechanism by which SFPQ promotes repeat RNA foci not defined\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Resolved the structural mechanism of cooperative RNA recognition and the SFPQ-NONO heterodimer architecture, mapping cancer mutations to the NOPS interface.\",\n      \"evidence\": \"Crystal structures of apo and RNA-bound SFPQ and of the SFPQ-NONO heterodimer\",\n      \"pmids\": [\"35998361\", \"35245601\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of NOPS-region cancer mutations untested\", \"Cooperativity in the cellular context not validated\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected familial ALS variants to enhanced zinc binding and a synaptic deficit, providing a structural mechanism for SFPQ aggregation in disease.\",\n      \"evidence\": \"Crystal structure of L534I, ITC zinc-binding affinity, primary neuron imaging, and GluA1/GluA2 surface quantification\",\n      \"pmids\": [\"36168806\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo pathogenicity of variants not demonstrated\", \"Link from aggregation to GluA1 reduction mechanistically incomplete\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established phase separation as a regulatory mode, showing SFPQ condensates sequester Smad4 to suppress TGF-\\u03b2 and that the two low-complexity regions oppositely tune condensation.\",\n      \"evidence\": \"LLPS assays, Co-IP, ChIP, reporter, and KO for Smad4 sequestration; in vitro condensation and FRAP with LCR-deletion constructs\",\n      \"pmids\": [\"38103553\", \"37952770\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How condensate formation is triggered by upstream signals unclear\", \"Relationship between Smad4 sequestration and paraspeckle condensates undefined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Expanded SFPQ into miRNA stability, viral life cycles, and a self-propagating neurodegenerative inclusion mechanism, diversifying its RNA-protective and pathological roles.\",\n      \"evidence\": \"BioID/small RNA-seq for miR-17~92 protection; CRISPR screen/KO and H1 ChIP for EBV latency; Co-IP/integration assay for HIV-1 integrase; patient brain fractionation and iPSC dopamine neurons for A-to-I-edited RNA inclusions\",\n      \"pmids\": [\"39250314\", \"38755141\", \"38373651\", \"38761794\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether viral and miRNA roles share a common biochemical basis unknown\", \"Trigger initiating PD inclusion seeding undefined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Refined polymerization mechanics, telomerase recruitment, and the ALS redistribution mechanism, showing coiled-coil plasticity drives tetramerization and an NLS-lacking isoform underlies cytoplasmic SFPQ.\",\n      \"evidence\": \"Crystallography/SAXS of SFPQ/NONO coiled-coil variants; hTR Co-IP with telomere length assays; RT-PCR/fractionation/proteomics of altSFPQ in ALS models\",\n      \"pmids\": [\"39698821\", \"40593584\", \"40845103\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Regulation of altSFPQ splicing choice unknown\", \"Telomerase recruitment role is single-lab and Co-IP-based\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SFPQ's many functions are partitioned\\u2014which heterodimer, modification state, and condensate context dictate transcription versus splicing versus DNA repair versus axonal transport in a given cell\\u2014remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking partner choice to functional output\", \"Physiological switches between nuclear and cytoplasmic SFPQ pools undefined\", \"Causal contribution of SFPQ mislocalization to human disease in vivo not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [3, 9, 15, 26]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 8]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 2, 25, 31]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [22, 11]},\n      {\"term_id\": \"GO:0140313\", \"supporting_discovery_ids\": [25]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [0, 1, 15]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [3, 12, 35, 39]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 2, 25]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 2, 25]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [4, 15, 32]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [5, 7, 8]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [25]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [3, 11]}\n    ],\n    \"complexes\": [\"SFPQ/NONO heterodimer\", \"SFPQ/PSPC1 heterodimer\", \"paraspeckle\", \"SFPQ-KIF5A/KLC1 transport complex\"],\n    \"partners\": [\"NONO\", \"PSPC1\", \"RAD51D\", \"FUS\", \"CDK9\", \"KIF5A\", \"Smad4\", \"FTO\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":8,"faith_pct":87.5}}