{"gene":"PUM1","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2008,"finding":"Human PUM1 binds a core consensus sequence UGUAHAUA in the 3' UTR of target mRNAs and enhances their decay; PUM1 also relocalizes to stress granules, suggesting a role in translational repression. Genome-wide ribonomic analysis identified mRNAs enriched for transcriptional regulators and cell cycle/proliferation factors as PUM1 targets, and PUM1 knockdown demonstrated increased stability of associated mRNAs.","method":"RNA immunoprecipitation (RIP) followed by microarray (ribonomic analysis); PUM1 knockdown with mRNA stability assays; immunofluorescence for stress granule localization","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-wide RIP, orthogonal knockdown + mRNA decay assay, localization experiment; multiple methods in single rigorous study","pmids":["18411299"],"is_preprint":false},{"year":2018,"finding":"PUM1 haploinsufficiency causes upregulation of known PUM1 target mRNAs/proteins in patient-derived cells; missense mutations reduce PUM1 protein levels (~25% reduction for adult-onset, ~50% reduction for infantile-onset disease), and the degree of reduction correlates with phenotypic severity. This establishes PUM1 as a dose-sensitive posttranscriptional repressor of its target mRNAs in neurons.","method":"Patient-derived cell studies; protein level quantification (Western blot); measurement of target mRNA/protein levels","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — patient-derived cells with quantitative protein and target measurements, replicated across multiple patients with dose-response relationship","pmids":["29474920"],"is_preprint":false},{"year":2019,"finding":"PUM1 (and PUM2) repress translation of CDKN1B (p27) by binding Pumilio binding elements (PBEs) in the 3' UTR, promoting G1-S transition and cell proliferation. Cdkn1b deficiency partially rescues the postnatal growth defects of Pum1-/- mice, establishing a genetic epistasis relationship.","method":"Pum1/Pum2 knockout mouse models; 3' UTR reporter assays; genetic rescue experiments (Pum1-/- × Cdkn1b-/- double mutants); Western blot for CDKN1B protein","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vivo genetic epistasis with double-mutant rescue, reporter assays, and protein-level measurements across multiple orthogonal approaches","pmids":["30811992"],"is_preprint":false},{"year":2019,"finding":"PUM1 knockdown in pancreatic cancer cells activates the PERK/eIF2/ATF4 signaling pathway, as shown by increased levels of p-PERK, p-EIF2A, and ATF4. PUM1 levels negatively correlate with p-PERK in PDAC tissues, and a PERK inhibitor rescues the anti-proliferative effects of PUM1 knockdown, placing PUM1 upstream of the PERK/eIF2 pathway.","method":"siRNA knockdown; cDNA microarray and pathway analysis; Western blot; PERK inhibitor rescue experiments; in vitro and in vivo (xenograft) assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knockdown with defined pathway readout and pharmacological rescue, single lab","pmids":["31395860"],"is_preprint":false},{"year":2017,"finding":"PUM1 acts as a negative regulator of innate immunity by repressing LGP2 expression. PUM1 depletion triggers a two-phase cascade: initial upregulation of LGP2, CXCL10, IL6, and PKR (phase 1), followed by upregulation of RIG-I, MDA5, IFIT1, IFNβ, and others (phase 2). Simultaneous depletion of PUM1 and LGP2 abrogates both phases, establishing LGP2 as the direct downstream mediator. PUM2 depletion does not reproduce these effects.","method":"siRNA knockdown of PUM1 alone and combinatorial knockdown of PUM1 + LGP2/CXCL10/IL6; RT-PCR for target gene expression; IFNβ functional assays; HSV-1 replication assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — combinatorial knockdown epistasis across multiple targets, PUM2 negative control, functional IFN assay; multiple orthogonal approaches","pmids":["28760986"],"is_preprint":false},{"year":2022,"finding":"PUM1 binds the 3' UTR of TLR4 mRNA to suppress its translation, thereby regulating NF-κB activity in human mesenchymal stem cells. PUM1 overexpression suppresses TLR4-mediated NF-κB signaling and protects against H2O2-induced senescence, while PUM1 knockdown activates TLR4-NF-κB signaling. The regulatory axis was confirmed in osteoarthritis models.","method":"RNA immunoprecipitation; 3' UTR binding assays; siRNA knockdown and overexpression; Western blot for TLR4 and NF-κB pathway; in vivo OA mouse model with lentiviral PUM1 gene therapy","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 / Strong — RIP demonstrates direct binding, overexpression and knockdown with signaling readouts, in vivo rescue model; multiple orthogonal methods","pmids":["35034101"],"is_preprint":false},{"year":2020,"finding":"PUM1 mediates decay of 48 specific target mRNAs identified by combined transcriptome-wide mRNA stability profiling and PUM1 binding data. DNA-damaging agents (e.g., cisplatin) reduce PUM1 abundance, leading to stabilization of PCNA and UBE2A mRNAs (involved in translesion synthesis). PUM1 overexpression impairs DNA synthesis and TLS and increases cisplatin sensitivity.","method":"Transcriptome-wide mRNA stability profiling (metabolic labeling); RIP-seq; RNA-seq; PUM1 overexpression and knockdown; cisplatin sensitivity assays; DNA synthesis assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — transcriptome-wide binding + stability profiling, functional overexpression with DNA damage readout; multiple orthogonal approaches in single study","pmids":["32375027"],"is_preprint":false},{"year":2022,"finding":"PUM1 directly binds γ-globin (HBG1) mRNA, reduces its stability and translational efficiency, thereby repressing fetal hemoglobin (HbF) production during erythroid differentiation. PUM1 expression is regulated by the erythroid transcription factor KLF1/EKLF and peaks during erythroid differentiation. PUM1 knockdown robustly increases HbF (~22%) without affecting β-globin levels.","method":"RNA immunoprecipitation (RIP); mRNA stability assays; translational efficiency assays; PUM1 knockdown in human erythroid cells; KLF1 regulation of PUM1 demonstrated; patient with heterozygous PUM1 RNA-binding domain mutation showing elevated HbF","journal":"Blood advances","confidence":"High","confidence_rationale":"Tier 2 / Strong — RIP, mRNA stability, translational efficiency assays, and human genetic validation; multiple orthogonal methods","pmids":["35667093"],"is_preprint":false},{"year":2019,"finding":"PUM1 directly binds the 3' UTR of LRP6 mRNA via RNA pull-down, RIP, and luciferase reporter assays, reducing LRP6 mRNA and protein expression. PUM1 repression of LRP6 restricts trophoblast proliferation and invasion; PUM1 depletion promotes these processes in an LRP6-dependent manner.","method":"RNA pull-down; RNA immunoprecipitation (RIP); luciferase reporter assay; RT-qPCR and Western blot; siRNA knockdown","journal":"Biochemistry and cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA pull-down, RIP, and reporter assay establish direct binding, but single lab","pmids":["34734756"],"is_preprint":false},{"year":2019,"finding":"PUM1 inhibits trophoblast invasion in preeclampsia by binding HOTAIR lncRNA and decreasing its half-life (destabilizing HOTAIR mRNA). RNA-protein pull-down and mRNA stability assays identified PUM1 as a specific binding partner that reduces the steady-state level of HOTAIR, establishing a posttranscriptional regulatory mechanism.","method":"RNA immunoprecipitation (RIP); RNA-protein pull-down; mRNA stability assays; lncRNA transcriptome sequencing; overexpression and knockdown of PUM1; villous explant culture model","journal":"Molecular therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP and pull-down with mRNA stability assay, but single lab with single target (HOTAIR)","pmids":["31862314"],"is_preprint":false},{"year":2021,"finding":"PUM1 represses CDKN1B (p27) at the translational level in prostate cancer cells. PUM1 knockdown elevates CDKN1B protein without changing its mRNA level; PUM1 overexpression reduces CDKN1B protein. PUM1 knockdown in vivo reduces tumor size.","method":"siRNA knockdown and overexpression of PUM1; Western blot and RT-qPCR for CDKN1B; subcutaneous xenograft mouse model","journal":"Journal of biomedical research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — bidirectional manipulation (KD + OE) with protein vs. mRNA dissociation confirms translational mechanism; single lab","pmids":["34531333"],"is_preprint":false},{"year":2018,"finding":"PUM1 exhibits PBE-independent repression of SIAH1 3' UTR (unlike PUM2 which requires PBEs), and the PUF domains of PUM1 and PUM2 show different EMSA complex formation patterns with SIAH1 3' UTRs. NANOS3 (but not NANOS2) directly binds SIAH1 3' UTR and cooperates with PUM1 in repression.","method":"Luciferase reporter assays with WT and PBE-mutant SIAH1 3' UTRs; EMSA (electrophoretic mobility shift assay); co-repression assays with NANOS paralogues","journal":"Cellular and molecular life sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — EMSA and reporter assays with mutagenesis establish mechanistic differences; single lab","pmids":["30269240"],"is_preprint":false},{"year":2020,"finding":"PUM1 and PUM2 form distinct RNP regulatory networks in human male germ cells (TCam-2), associating with different sets of protein cofactors (identified by mass spectrometry) and regulating partially overlapping but distinct mRNA pools (identified by RIP-Seq). This indicates functional divergence between the two paralogs despite highly similar RNA-binding domains.","method":"RIP-Seq; RNA-Seq; global mass spectrometry-based protein cofactor profiling; RNA motif enrichment analysis","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP-Seq and MS interactome establish distinct cofactor networks; single lab, single cell model","pmids":["32316190"],"is_preprint":false},{"year":2022,"finding":"NANOS3 in complex with PUM1 causes 3' UTR-mediated repression of FOXM1 mRNA, which encodes a transcription factor required for G2/M phase transition. This establishes PUM1 as part of a NANOS3-PUM1 post-transcriptional repressor complex targeting FOXM1 to regulate G2/M progression in human primordial germ cells.","method":"RNA-sequencing; 3' UTR reporter assays; overexpression of NANOS3 and PUM1 in TCam-2 cells; cell cycle analysis","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — 3' UTR reporter and cell cycle assays establish functional complex; single lab","pmids":["35743036"],"is_preprint":false},{"year":2023,"finding":"PUM1 binds directly to the Pumilio response element (PRE) in DEPTOR mRNA to maintain transcript stability (preventing its degradation), which leads to DEPTOR upregulation, mTORC1 inhibition, and relief of inhibitory feedback to PI3K, thus activating PI3K-Akt signaling and glycolysis in gastric cancer cells.","method":"RNA immunoprecipitation; RNA-sequencing; metabolomics; PUM1 knockdown in vitro and in vivo; Western blot for mTORC1/PI3K-Akt pathway components","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP establishes direct binding and mRNA stability role; metabolomics and pathway analyses are orthogonal; single lab","pmids":["37469018"],"is_preprint":false},{"year":2021,"finding":"PUM1 interacts with DDX5 in the 3' UTR and positively regulates DDX5 mRNA expression in cetuximab-resistant colon cancer cells. PUM1 knockout reduced DDX5 levels and decreased cell viability in the presence of cetuximab.","method":"CRISPR-Cas9 knockout of PUM1 and DDX5; qPCR and immunoblot; co-immunoprecipitation; Cell Counting Kit-8 proliferation assay","journal":"Frontiers in cell and developmental biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (co-IP) for interaction; mechanism of positive regulation not deeply characterized","pmids":["34447749"],"is_preprint":false},{"year":2024,"finding":"A chromosomal translocation creates a PUM1-TRAF3 fusion protein that activates non-canonical NF-κB signaling via competitive binding to NF-κB-inducing kinase (NIK), preventing TRAF3-mediated NIK degradation and enabling P52/RelB nuclear translocation. An NIK inhibitor reverses these effects.","method":"RNA-sequencing for fusion gene identification; FISH for validation; establishment of PUM1-TRAF3-expressing BTC cell lines; molecular pathway analysis; NIK inhibitor rescue experiments","journal":"NPJ precision oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional cell lines with molecular mechanism established and pharmacological rescue; single lab","pmids":["39090283"],"is_preprint":false},{"year":2025,"finding":"HIF1α transcriptionally activates PUM1 by directly binding its promoter under hypoxia. PUM1 then binds and destabilizes KCNK3 mRNA, reducing KCNK3 protein in pulmonary artery smooth muscle cells. In vivo AAV9-mediated PUM1 knockdown attenuated pulmonary hypertension, while PUM1 overexpression exacerbated it. HIF1α knockdown increased KCNK3 mRNA stability and reduced PUM1-KCNK3 mRNA interaction.","method":"ChIP for HIF1α binding to PUM1 promoter; RIP for PUM1-KCNK3 mRNA interaction; mRNA stability assays; AAV9-mediated in vivo knockdown; overexpression experiments; rat PH models","journal":"Biochimica et biophysica acta. Molecular basis of disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP, RIP, mRNA stability assay, and in vivo model; single lab with multiple orthogonal methods","pmids":["41135634"],"is_preprint":false},{"year":2025,"finding":"PUM1-mediated mRNA decay requires the CCR4-NOT deadenylase complex (not the PAN deadenylase) and depends on the poly(A) tail. PUM1 associates with and requires PABPC1 and PABPC4 to repress target mRNAs. Increasing PABPC concentration inhibits PUM1 activity in a concentration-dependent manner by protecting poly(A) from deadenylation, establishing a tunable regulatory mechanism.","method":"Biochemical reconstitution; deadenylase requirement assays; PABPC co-immunoprecipitation; PABPC titration experiments; mRNA decay assays","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — reconstitution and biochemical assays are Tier 1, but preprint not yet peer-reviewed; single lab","pmids":["bio_10.1101_2025.10.02.680050"],"is_preprint":true},{"year":2024,"finding":"PUM1 binds CCR4-NOT through intrinsically disordered regions (IDRs) via multivalent interactions at several distinct binding sites. Phosphorylation within IDRs modulates PUM1 binding to CCR4-NOT and consequently tunes the mRNA deadenylation rate in a continuously graded (not binary) manner, as demonstrated by biochemical reconstitution and structural analysis.","method":"Structural biology; biochemical reconstitution; phosphorylation-dependent binding assays; in vitro deadenylation assays with WT and phosphomimetic/phosphoablative PUM1 IDR variants","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — reconstitution and structural biology are Tier 1, but preprint not yet peer-reviewed; single lab","pmids":["bio_10.1101_2024.10.18.618793"],"is_preprint":true},{"year":2025,"finding":"PUM1 enhances PAK6 mRNA stability by binding to PAK6 mRNA (demonstrated by RIP and luciferase assay), thereby promoting ferroptosis resistance in lung adenocarcinoma cells. PUM1 silencing promotes ferroptosis both in vitro and in vivo, and this effect is reversed by artificial restoration of PAK6.","method":"RNA immunoprecipitation; luciferase assay; PUM1/PAK6 knockdown; ferroptosis assays (Fe2+, MDA levels); in vivo xenograft model","journal":"Pathology, research and practice","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP and reporter assay for direct binding, in vitro and in vivo functional rescue; single lab","pmids":["40694989"],"is_preprint":false},{"year":2014,"finding":"PUM1 silencing in pancreatic cancer cells increases p27 (CDKN1B) expression and the amount of the p27-CDK2 complex, as shown by immunoprecipitation. PUM1 overexpression attenuates TRAIL-induced effects, while PUM1 silencing enhances autophagy activation and TRAIL sensitivity.","method":"siRNA knockdown; immunoprecipitation (p27-CDK2 complex); Western blot; proliferation and apoptosis assays; in vivo xenograft","journal":"Phytomedicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP showing p27-CDK2 complex change; single lab, indirect pathway evidence","pmids":["31128486"],"is_preprint":false},{"year":2023,"finding":"PUM1 regulates macrophage polarization via the PUM1/Cripto-1 pathway: PUM1 negatively regulates Cripto-1 expression and promotes M1-type macrophage polarization. Allogeneic blood transfusion inhibits ferroptosis in macrophages through effects on this pathway.","method":"RT-qPCR; Western blot; in vivo mouse model; in vitro RAW264.7 cell experiments; macrophage polarization marker analysis; JC-1 staining","journal":"Aging","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, primarily expression-level evidence with no direct binding or epistasis for PUM1-Cripto-1 mechanism","pmids":["37387538"],"is_preprint":false},{"year":2025,"finding":"PUM1 depletion mildly increases intracellular SARS-CoV-2 viral RNA levels, suggesting a mild antiviral or host-factor regulatory role. PUM1 also negatively regulates innate immunity gene expression both at steady state and during SARS-CoV-2 infection. However, altering PUM1 levels does not affect progeny virion production.","method":"siRNA/shRNA depletion; viral RNA quantification; innate immunity gene expression assays; progeny virion production assays (plaque/TCID50)","journal":"The Journal of general virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with quantitative viral and immune gene readouts; negative result for virion production explicitly noted; single lab","pmids":["40956600"],"is_preprint":false}],"current_model":"PUM1 is a sequence-specific RNA-binding protein that recognizes the consensus motif UGUAHAUA in 3' UTRs of target mRNAs to repress their stability and/or translation via recruitment of the CCR4-NOT deadenylase complex (modulated by phosphorylation and PABPC availability); validated targets include CDKN1B/p27 (controlling cell proliferation and body size), TLR4 (regulating NF-κB-mediated cellular aging), LGP2 (suppressing innate immunity in a two-phase cascade), γ-globin HBG1 (mediating hemoglobin switching), KCNK3 (driven by HIF1α in pulmonary hypertension), HOTAIR lncRNA (restricting trophoblast invasion), DEPTOR (activating PI3K-Akt glycolysis), and PAK6 (conferring ferroptosis resistance), with PUM1's activity modulated by cofactors such as NANOS proteins and tuned by phosphorylation of its intrinsically disordered regions."},"narrative":{"mechanistic_narrative":"PUM1 is a sequence-specific RNA-binding protein that recognizes a UGUAHAUA consensus motif in the 3' UTRs of target mRNAs and acts as a dose-sensitive post-transcriptional repressor controlling cell proliferation, innate immunity, and development [PMID:18411299, PMID:29474920]. Mechanistically, PUM1 destabilizes bound transcripts by recruiting the CCR4-NOT deadenylase complex (not the PAN deadenylase) in a poly(A)-tail-dependent manner, and its repressive output is continuously tunable: phosphorylation within PUM1's intrinsically disordered regions graded­ly modulates multivalent CCR4-NOT binding, and rising PABPC1/PABPC4 concentrations protect the poly(A) tail to dampen PUM1 activity [PMID:bio_10.1101_2025.10.02.680050, PMID:bio_10.1101_2024.10.18.618793]. PUM1 can also repress targets at the translational level without altering mRNA abundance, as shown for CDKN1B/p27, and can cooperate with NANOS cofactors to confer target specificity [PMID:34531333, PMID:30269240, PMID:35743036]. Through CDKN1B/p27 repression PUM1 promotes the G1-S transition and controls postnatal growth, a relationship established by genetic epistasis in which Cdkn1b loss rescues Pum1-null growth defects [PMID:30811992]. Beyond proliferation, PUM1 restrains innate immunity by repressing LGP2 to suppress a two-phase interferon cascade [PMID:28760986], suppresses TLR4-NF-κB signaling to protect against oxidative senescence [PMID:35034101], and represses γ-globin (HBG1) to drive fetal-to-adult hemoglobin switching during erythroid differentiation [PMID:35667093]. PUM1 expression is itself regulated by upstream factors including KLF1 in erythroid cells and HIF1α under hypoxia [PMID:35667093, PMID:41135634]. PUM1 haploinsufficiency, through reduced protein levels that correlate with phenotypic severity, causes a dose-dependent neurological disorder [PMID:29474920].","teleology":[{"year":2008,"claim":"Established the founding biochemical identity of human PUM1: what sequence it recognizes and what it does to bound transcripts.","evidence":"Genome-wide RIP-microarray plus knockdown mRNA-stability assays and stress granule immunofluorescence","pmids":["18411299"],"confidence":"High","gaps":["Did not resolve the deadenylase machinery used for decay","Translational repression inferred from localization, not directly measured"]},{"year":2019,"claim":"Connected PUM1 to a defined proliferative output by showing it represses CDKN1B/p27 and that this relationship is genetically epistatic for growth control.","evidence":"Pum1/Pum2 knockout mice, 3' UTR reporters, and Pum1-/- x Cdkn1b-/- double-mutant rescue","pmids":["30811992"],"confidence":"High","gaps":["Did not separate translational vs decay contributions at CDKN1B in vivo","Tissue specificity of the epistasis not fully mapped"]},{"year":2017,"claim":"Defined PUM1 as a negative regulator of innate immunity by placing LGP2 as the direct downstream mediator of a two-phase interferon cascade, distinguishing PUM1 from PUM2.","evidence":"Combinatorial siRNA epistasis (PUM1+LGP2), interferon functional assays, HSV-1 replication, PUM2 negative control","pmids":["28760986"],"confidence":"High","gaps":["Direct PUM1 binding to LGP2 3' UTR not biochemically shown in this study","Physiological trigger that relieves PUM1 repression unknown"]},{"year":2018,"claim":"Established PUM1 as a dose-sensitive repressor whose protein level quantitatively determines phenotypic severity, linking it to human disease.","evidence":"Patient-derived cells with quantitative protein/target measurements and dose-response correlation across patients","pmids":["29474920"],"confidence":"High","gaps":["Which neuronal targets drive each phenotype not fully resolved","Molecular basis of missense-induced protein destabilization not characterized"]},{"year":2020,"claim":"Showed PUM1 controls a discrete decay regulon coupled to DNA damage, defining a context where PUM1 abundance is itself regulated to alter target stability.","evidence":"Transcriptome-wide stability profiling plus RIP-seq, with cisplatin sensitivity and DNA synthesis assays","pmids":["32375027"],"confidence":"High","gaps":["Mechanism reducing PUM1 abundance after DNA damage unresolved","Direct binding to all 48 targets not individually validated"]},{"year":2022,"claim":"Demonstrated PUM1 represses HBG1 to govern hemoglobin switching and is transcriptionally driven by KLF1, embedding it in erythroid gene regulation.","evidence":"RIP, mRNA stability and translational efficiency assays, erythroid knockdown, plus a patient with an RNA-binding-domain mutation and elevated HbF","pmids":["35667093"],"confidence":"High","gaps":["Relative weight of decay vs translational repression at HBG1 not quantified","Whether HbF derepression is therapeutically tractable not addressed"]},{"year":2022,"claim":"Linked PUM1 to TLR4-NF-κB-driven cellular senescence, defining a protective post-transcriptional axis confirmed in disease models.","evidence":"RIP and 3' UTR binding, bidirectional manipulation with NF-κB readouts, and in vivo osteoarthritis gene therapy","pmids":["35034101"],"confidence":"High","gaps":["Whether repression is translational or decay-based at TLR4 not dissected","Upstream control of PUM1 in senescence unknown"]},{"year":2018,"claim":"Revealed that PUM1 specificity and cofactor cooperation diverge from PUM2, including PBE-independent repression and NANOS3 partnership.","evidence":"Reporter assays with PBE-mutant 3' UTRs, EMSA, and NANOS paralog co-repression assays","pmids":["30269240"],"confidence":"Medium","gaps":["Structural basis of PBE-independent binding not defined","Single target (SIAH1) and single lab"]},{"year":2020,"claim":"Showed PUM1 and PUM2 build distinct RNP networks with different cofactors and target pools, formalizing paralog functional divergence.","evidence":"RIP-seq, RNA-seq, and mass spectrometry interactome in TCam-2 germ cells","pmids":["32316190"],"confidence":"Medium","gaps":["Single cell model limits generality","Functional consequences of distinct cofactor sets not tested"]},{"year":2024,"claim":"Provided the structural-biochemical basis for how PUM1 recruits CCR4-NOT and how phosphorylation tunes deadenylation in a graded manner.","evidence":"Structural biology and reconstituted in vitro deadenylation with phosphomimetic/phosphoablative IDR variants (preprint)","pmids":["bio_10.1101_2024.10.18.618793"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Kinases responsible for PUM1 IDR phosphorylation in vivo not identified"]},{"year":2025,"claim":"Defined the deadenylase requirement and PABPC-based tunability of PUM1-mediated decay, completing the core repression mechanism.","evidence":"Biochemical reconstitution, deadenylase-requirement assays, PABPC co-IP and titration (preprint)","pmids":["bio_10.1101_2025.10.02.680050"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Whether PABPC tuning operates at endogenous targets in cells not shown"]},{"year":2025,"claim":"Expanded the regulatory hierarchy by showing HIF1α transcriptionally induces PUM1 to destabilize KCNK3 in pulmonary hypertension.","evidence":"ChIP for HIF1α-promoter binding, RIP, mRNA stability assays, and AAV9 in vivo knockdown in rat PH models","pmids":["41135634"],"confidence":"Medium","gaps":["Single lab","Translational vs decay contribution at KCNK3 not separated"]},{"year":2023,"claim":"Showed PUM1 can stabilize rather than degrade certain targets (DEPTOR), revealing context-dependent positive regulation feeding into PI3K-Akt/glycolysis.","evidence":"RIP, RNA-seq, metabolomics, and in vitro/in vivo knockdown in gastric cancer","pmids":["37469018"],"confidence":"Medium","gaps":["Mechanism by which PUM1 stabilizes (vs destabilizes) DEPTOR unresolved","Single lab and cancer-specific context"]},{"year":null,"claim":"How PUM1 switches between destabilizing and stabilizing target mRNAs, and which upstream kinases set its phosphorylation-dependent activity in specific cell types, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model reconciling decay (e.g. HBG1, KCNK3) vs stabilization (DEPTOR, PAK6) outcomes","Kinases and signals controlling PUM1 IDR phosphorylation in vivo unidentified","In-cell validation of PABPC tunability still pending peer review"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,5,7,9,14,17,20]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[0,6,18]},{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[2,10]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[18,19]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,6,18,19]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[4,5,23]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2,13]}],"complexes":["CCR4-NOT deadenylase complex","NANOS3-PUM1 repressor complex"],"partners":["NANOS3","PABPC1","PABPC4","PUM2","DDX5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q14671","full_name":"Pumilio homolog 1","aliases":[],"length_aa":1186,"mass_kda":126.5,"function":"Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (PubMed:18328718, PubMed:21397187, PubMed:21572425, PubMed:21653694). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233)","subcellular_location":"Cytoplasm; Cytoplasm, P-body; Cytoplasmic granule","url":"https://www.uniprot.org/uniprotkb/Q14671/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PUM1","classification":"Not Classified","n_dependent_lines":186,"n_total_lines":1208,"dependency_fraction":0.15397350993377484},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPZB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/PUM1","total_profiled":1310},"omim":[{"mim_id":"620719","title":"NEURODEVELOPMENTAL DISORDER WITH MOTOR ABNORMALITIES, SEIZURES, AND FACIAL DYSMORPHISM; NEDMSF","url":"https://www.omim.org/entry/620719"},{"mim_id":"620174","title":"SPINOCEREBELLAR ATAXIA 27B, LATE-ONSET; SCA27B","url":"https://www.omim.org/entry/620174"},{"mim_id":"617930","title":"CHROMOSOME 1p35 DELETION SYNDROME","url":"https://www.omim.org/entry/617930"},{"mim_id":"617037","title":"NONCODING RNA ACTIVATED BY DNA DAMAGE; NORAD","url":"https://www.omim.org/entry/617037"},{"mim_id":"607205","title":"PUMILIO RNA BINDING FAMILY MEMBER 2; PUM2","url":"https://www.omim.org/entry/607205"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Cytosol","reliability":"Enhanced"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PUM1"},"hgnc":{"alias_symbol":["PUMH1","KIAA0099"],"prev_symbol":[]},"alphafold":{"accession":"Q14671","domains":[{"cath_id":"-","chopping":"841-921","consensus_level":"medium","plddt":96.9253,"start":841,"end":921},{"cath_id":"1.25.40","chopping":"1069-1175","consensus_level":"medium","plddt":92.5849,"start":1069,"end":1175}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14671","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q14671-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q14671-F1-predicted_aligned_error_v6.png","plddt_mean":52.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PUM1","jax_strain_url":"https://www.jax.org/strain/search?query=PUM1"},"sequence":{"accession":"Q14671","fasta_url":"https://rest.uniprot.org/uniprotkb/Q14671.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q14671/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14671"}},"corpus_meta":[{"pmid":"18411299","id":"PMC_18411299","title":"Ribonomic 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Molecular basis of disease","url":"https://pubmed.ncbi.nlm.nih.gov/41135634","citation_count":1,"is_preprint":false},{"pmid":"40956600","id":"PMC_40956600","title":"PUM2 binds SARS-CoV-2 RNA and PUM1 mildly reduces viral RNA levels, but neither protein affects progeny virus production.","date":"2025","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/40956600","citation_count":1,"is_preprint":false},{"pmid":"40694989","id":"PMC_40694989","title":"PUM1 enhances PAK6 mRNA stability and contributes to growth and ferroptosis resistance in lung adenocarcinoma cells.","date":"2025","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/40694989","citation_count":0,"is_preprint":false},{"pmid":"41908224","id":"PMC_41908224","title":"Evaluation of the circular RNA Pum1_0014, miRNA-146a, and miRNA-141-3p as biomarkers in PCOS.","date":"2026","source":"Journal of Taibah University Medical Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41908224","citation_count":0,"is_preprint":false},{"pmid":"40666984","id":"PMC_40666984","title":"PUM2 binds SARS-CoV-2 RNA and PUM1 mildly reduces viral RNA levels, but neither protein affects progeny virus production.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40666984","citation_count":0,"is_preprint":false},{"pmid":"41912775","id":"PMC_41912775","title":"Fusobacterium nucleatum drives colorectal cancer progression through the circPTBP3/miR-760/PUM1 axis.","date":"2026","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/41912775","citation_count":0,"is_preprint":false},{"pmid":"33241107","id":"PMC_33241107","title":"Repression of PUM1-mediated mRNA decay activates translesion synthesis after DNA damage.","date":"2020","source":"Molecular & cellular oncology","url":"https://pubmed.ncbi.nlm.nih.gov/33241107","citation_count":0,"is_preprint":false},{"pmid":"41342067","id":"PMC_41342067","title":"Retraction Note: MiR-411-5p acts as a tumor suppressor in non-small cell lung cancer through targeting PUM1.","date":"2025","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41342067","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.27.691032","title":"Viral non-coding RNAs hijack host Pumilio proteins to regulate host transcripts","date":"2025-12-01","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.27.691032","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.10.02.680050","title":"Cytoplasmic poly-adenosine binding proteins modulate susceptibility of mRNAs to RNA-binding protein-directed decay","date":"2025-10-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.02.680050","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.10.11.681827","title":"PUMILIOs and m6A-ECT2/ECT3 share mRNA targets and exert opposing control over organogenesis","date":"2025-10-12","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.11.681827","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.18.618793","title":"Phosphorylation-dependent tuning of mRNA deadenylation rates","date":"2024-10-19","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.18.618793","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":31152,"output_tokens":6413,"usd":0.094825,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":15322,"output_tokens":4168,"usd":0.090405,"stage2_stop_reason":"end_turn"},"total_usd":0.18523,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2008,\n      \"finding\": \"Human PUM1 binds a core consensus sequence UGUAHAUA in the 3' UTR of target mRNAs and enhances their decay; PUM1 also relocalizes to stress granules, suggesting a role in translational repression. Genome-wide ribonomic analysis identified mRNAs enriched for transcriptional regulators and cell cycle/proliferation factors as PUM1 targets, and PUM1 knockdown demonstrated increased stability of associated mRNAs.\",\n      \"method\": \"RNA immunoprecipitation (RIP) followed by microarray (ribonomic analysis); PUM1 knockdown with mRNA stability assays; immunofluorescence for stress granule localization\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-wide RIP, orthogonal knockdown + mRNA decay assay, localization experiment; multiple methods in single rigorous study\",\n      \"pmids\": [\"18411299\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PUM1 haploinsufficiency causes upregulation of known PUM1 target mRNAs/proteins in patient-derived cells; missense mutations reduce PUM1 protein levels (~25% reduction for adult-onset, ~50% reduction for infantile-onset disease), and the degree of reduction correlates with phenotypic severity. This establishes PUM1 as a dose-sensitive posttranscriptional repressor of its target mRNAs in neurons.\",\n      \"method\": \"Patient-derived cell studies; protein level quantification (Western blot); measurement of target mRNA/protein levels\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — patient-derived cells with quantitative protein and target measurements, replicated across multiple patients with dose-response relationship\",\n      \"pmids\": [\"29474920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PUM1 (and PUM2) repress translation of CDKN1B (p27) by binding Pumilio binding elements (PBEs) in the 3' UTR, promoting G1-S transition and cell proliferation. Cdkn1b deficiency partially rescues the postnatal growth defects of Pum1-/- mice, establishing a genetic epistasis relationship.\",\n      \"method\": \"Pum1/Pum2 knockout mouse models; 3' UTR reporter assays; genetic rescue experiments (Pum1-/- × Cdkn1b-/- double mutants); Western blot for CDKN1B protein\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vivo genetic epistasis with double-mutant rescue, reporter assays, and protein-level measurements across multiple orthogonal approaches\",\n      \"pmids\": [\"30811992\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PUM1 knockdown in pancreatic cancer cells activates the PERK/eIF2/ATF4 signaling pathway, as shown by increased levels of p-PERK, p-EIF2A, and ATF4. PUM1 levels negatively correlate with p-PERK in PDAC tissues, and a PERK inhibitor rescues the anti-proliferative effects of PUM1 knockdown, placing PUM1 upstream of the PERK/eIF2 pathway.\",\n      \"method\": \"siRNA knockdown; cDNA microarray and pathway analysis; Western blot; PERK inhibitor rescue experiments; in vitro and in vivo (xenograft) assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knockdown with defined pathway readout and pharmacological rescue, single lab\",\n      \"pmids\": [\"31395860\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PUM1 acts as a negative regulator of innate immunity by repressing LGP2 expression. PUM1 depletion triggers a two-phase cascade: initial upregulation of LGP2, CXCL10, IL6, and PKR (phase 1), followed by upregulation of RIG-I, MDA5, IFIT1, IFNβ, and others (phase 2). Simultaneous depletion of PUM1 and LGP2 abrogates both phases, establishing LGP2 as the direct downstream mediator. PUM2 depletion does not reproduce these effects.\",\n      \"method\": \"siRNA knockdown of PUM1 alone and combinatorial knockdown of PUM1 + LGP2/CXCL10/IL6; RT-PCR for target gene expression; IFNβ functional assays; HSV-1 replication assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — combinatorial knockdown epistasis across multiple targets, PUM2 negative control, functional IFN assay; multiple orthogonal approaches\",\n      \"pmids\": [\"28760986\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PUM1 binds the 3' UTR of TLR4 mRNA to suppress its translation, thereby regulating NF-κB activity in human mesenchymal stem cells. PUM1 overexpression suppresses TLR4-mediated NF-κB signaling and protects against H2O2-induced senescence, while PUM1 knockdown activates TLR4-NF-κB signaling. The regulatory axis was confirmed in osteoarthritis models.\",\n      \"method\": \"RNA immunoprecipitation; 3' UTR binding assays; siRNA knockdown and overexpression; Western blot for TLR4 and NF-κB pathway; in vivo OA mouse model with lentiviral PUM1 gene therapy\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RIP demonstrates direct binding, overexpression and knockdown with signaling readouts, in vivo rescue model; multiple orthogonal methods\",\n      \"pmids\": [\"35034101\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PUM1 mediates decay of 48 specific target mRNAs identified by combined transcriptome-wide mRNA stability profiling and PUM1 binding data. DNA-damaging agents (e.g., cisplatin) reduce PUM1 abundance, leading to stabilization of PCNA and UBE2A mRNAs (involved in translesion synthesis). PUM1 overexpression impairs DNA synthesis and TLS and increases cisplatin sensitivity.\",\n      \"method\": \"Transcriptome-wide mRNA stability profiling (metabolic labeling); RIP-seq; RNA-seq; PUM1 overexpression and knockdown; cisplatin sensitivity assays; DNA synthesis assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — transcriptome-wide binding + stability profiling, functional overexpression with DNA damage readout; multiple orthogonal approaches in single study\",\n      \"pmids\": [\"32375027\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PUM1 directly binds γ-globin (HBG1) mRNA, reduces its stability and translational efficiency, thereby repressing fetal hemoglobin (HbF) production during erythroid differentiation. PUM1 expression is regulated by the erythroid transcription factor KLF1/EKLF and peaks during erythroid differentiation. PUM1 knockdown robustly increases HbF (~22%) without affecting β-globin levels.\",\n      \"method\": \"RNA immunoprecipitation (RIP); mRNA stability assays; translational efficiency assays; PUM1 knockdown in human erythroid cells; KLF1 regulation of PUM1 demonstrated; patient with heterozygous PUM1 RNA-binding domain mutation showing elevated HbF\",\n      \"journal\": \"Blood advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RIP, mRNA stability, translational efficiency assays, and human genetic validation; multiple orthogonal methods\",\n      \"pmids\": [\"35667093\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PUM1 directly binds the 3' UTR of LRP6 mRNA via RNA pull-down, RIP, and luciferase reporter assays, reducing LRP6 mRNA and protein expression. PUM1 repression of LRP6 restricts trophoblast proliferation and invasion; PUM1 depletion promotes these processes in an LRP6-dependent manner.\",\n      \"method\": \"RNA pull-down; RNA immunoprecipitation (RIP); luciferase reporter assay; RT-qPCR and Western blot; siRNA knockdown\",\n      \"journal\": \"Biochemistry and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA pull-down, RIP, and reporter assay establish direct binding, but single lab\",\n      \"pmids\": [\"34734756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PUM1 inhibits trophoblast invasion in preeclampsia by binding HOTAIR lncRNA and decreasing its half-life (destabilizing HOTAIR mRNA). RNA-protein pull-down and mRNA stability assays identified PUM1 as a specific binding partner that reduces the steady-state level of HOTAIR, establishing a posttranscriptional regulatory mechanism.\",\n      \"method\": \"RNA immunoprecipitation (RIP); RNA-protein pull-down; mRNA stability assays; lncRNA transcriptome sequencing; overexpression and knockdown of PUM1; villous explant culture model\",\n      \"journal\": \"Molecular therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP and pull-down with mRNA stability assay, but single lab with single target (HOTAIR)\",\n      \"pmids\": [\"31862314\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PUM1 represses CDKN1B (p27) at the translational level in prostate cancer cells. PUM1 knockdown elevates CDKN1B protein without changing its mRNA level; PUM1 overexpression reduces CDKN1B protein. PUM1 knockdown in vivo reduces tumor size.\",\n      \"method\": \"siRNA knockdown and overexpression of PUM1; Western blot and RT-qPCR for CDKN1B; subcutaneous xenograft mouse model\",\n      \"journal\": \"Journal of biomedical research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — bidirectional manipulation (KD + OE) with protein vs. mRNA dissociation confirms translational mechanism; single lab\",\n      \"pmids\": [\"34531333\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PUM1 exhibits PBE-independent repression of SIAH1 3' UTR (unlike PUM2 which requires PBEs), and the PUF domains of PUM1 and PUM2 show different EMSA complex formation patterns with SIAH1 3' UTRs. NANOS3 (but not NANOS2) directly binds SIAH1 3' UTR and cooperates with PUM1 in repression.\",\n      \"method\": \"Luciferase reporter assays with WT and PBE-mutant SIAH1 3' UTRs; EMSA (electrophoretic mobility shift assay); co-repression assays with NANOS paralogues\",\n      \"journal\": \"Cellular and molecular life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — EMSA and reporter assays with mutagenesis establish mechanistic differences; single lab\",\n      \"pmids\": [\"30269240\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PUM1 and PUM2 form distinct RNP regulatory networks in human male germ cells (TCam-2), associating with different sets of protein cofactors (identified by mass spectrometry) and regulating partially overlapping but distinct mRNA pools (identified by RIP-Seq). This indicates functional divergence between the two paralogs despite highly similar RNA-binding domains.\",\n      \"method\": \"RIP-Seq; RNA-Seq; global mass spectrometry-based protein cofactor profiling; RNA motif enrichment analysis\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP-Seq and MS interactome establish distinct cofactor networks; single lab, single cell model\",\n      \"pmids\": [\"32316190\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NANOS3 in complex with PUM1 causes 3' UTR-mediated repression of FOXM1 mRNA, which encodes a transcription factor required for G2/M phase transition. This establishes PUM1 as part of a NANOS3-PUM1 post-transcriptional repressor complex targeting FOXM1 to regulate G2/M progression in human primordial germ cells.\",\n      \"method\": \"RNA-sequencing; 3' UTR reporter assays; overexpression of NANOS3 and PUM1 in TCam-2 cells; cell cycle analysis\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — 3' UTR reporter and cell cycle assays establish functional complex; single lab\",\n      \"pmids\": [\"35743036\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PUM1 binds directly to the Pumilio response element (PRE) in DEPTOR mRNA to maintain transcript stability (preventing its degradation), which leads to DEPTOR upregulation, mTORC1 inhibition, and relief of inhibitory feedback to PI3K, thus activating PI3K-Akt signaling and glycolysis in gastric cancer cells.\",\n      \"method\": \"RNA immunoprecipitation; RNA-sequencing; metabolomics; PUM1 knockdown in vitro and in vivo; Western blot for mTORC1/PI3K-Akt pathway components\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP establishes direct binding and mRNA stability role; metabolomics and pathway analyses are orthogonal; single lab\",\n      \"pmids\": [\"37469018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PUM1 interacts with DDX5 in the 3' UTR and positively regulates DDX5 mRNA expression in cetuximab-resistant colon cancer cells. PUM1 knockout reduced DDX5 levels and decreased cell viability in the presence of cetuximab.\",\n      \"method\": \"CRISPR-Cas9 knockout of PUM1 and DDX5; qPCR and immunoblot; co-immunoprecipitation; Cell Counting Kit-8 proliferation assay\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (co-IP) for interaction; mechanism of positive regulation not deeply characterized\",\n      \"pmids\": [\"34447749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A chromosomal translocation creates a PUM1-TRAF3 fusion protein that activates non-canonical NF-κB signaling via competitive binding to NF-κB-inducing kinase (NIK), preventing TRAF3-mediated NIK degradation and enabling P52/RelB nuclear translocation. An NIK inhibitor reverses these effects.\",\n      \"method\": \"RNA-sequencing for fusion gene identification; FISH for validation; establishment of PUM1-TRAF3-expressing BTC cell lines; molecular pathway analysis; NIK inhibitor rescue experiments\",\n      \"journal\": \"NPJ precision oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional cell lines with molecular mechanism established and pharmacological rescue; single lab\",\n      \"pmids\": [\"39090283\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"HIF1α transcriptionally activates PUM1 by directly binding its promoter under hypoxia. PUM1 then binds and destabilizes KCNK3 mRNA, reducing KCNK3 protein in pulmonary artery smooth muscle cells. In vivo AAV9-mediated PUM1 knockdown attenuated pulmonary hypertension, while PUM1 overexpression exacerbated it. HIF1α knockdown increased KCNK3 mRNA stability and reduced PUM1-KCNK3 mRNA interaction.\",\n      \"method\": \"ChIP for HIF1α binding to PUM1 promoter; RIP for PUM1-KCNK3 mRNA interaction; mRNA stability assays; AAV9-mediated in vivo knockdown; overexpression experiments; rat PH models\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular basis of disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP, RIP, mRNA stability assay, and in vivo model; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"41135634\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PUM1-mediated mRNA decay requires the CCR4-NOT deadenylase complex (not the PAN deadenylase) and depends on the poly(A) tail. PUM1 associates with and requires PABPC1 and PABPC4 to repress target mRNAs. Increasing PABPC concentration inhibits PUM1 activity in a concentration-dependent manner by protecting poly(A) from deadenylation, establishing a tunable regulatory mechanism.\",\n      \"method\": \"Biochemical reconstitution; deadenylase requirement assays; PABPC co-immunoprecipitation; PABPC titration experiments; mRNA decay assays\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — reconstitution and biochemical assays are Tier 1, but preprint not yet peer-reviewed; single lab\",\n      \"pmids\": [\"bio_10.1101_2025.10.02.680050\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PUM1 binds CCR4-NOT through intrinsically disordered regions (IDRs) via multivalent interactions at several distinct binding sites. Phosphorylation within IDRs modulates PUM1 binding to CCR4-NOT and consequently tunes the mRNA deadenylation rate in a continuously graded (not binary) manner, as demonstrated by biochemical reconstitution and structural analysis.\",\n      \"method\": \"Structural biology; biochemical reconstitution; phosphorylation-dependent binding assays; in vitro deadenylation assays with WT and phosphomimetic/phosphoablative PUM1 IDR variants\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — reconstitution and structural biology are Tier 1, but preprint not yet peer-reviewed; single lab\",\n      \"pmids\": [\"bio_10.1101_2024.10.18.618793\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PUM1 enhances PAK6 mRNA stability by binding to PAK6 mRNA (demonstrated by RIP and luciferase assay), thereby promoting ferroptosis resistance in lung adenocarcinoma cells. PUM1 silencing promotes ferroptosis both in vitro and in vivo, and this effect is reversed by artificial restoration of PAK6.\",\n      \"method\": \"RNA immunoprecipitation; luciferase assay; PUM1/PAK6 knockdown; ferroptosis assays (Fe2+, MDA levels); in vivo xenograft model\",\n      \"journal\": \"Pathology, research and practice\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP and reporter assay for direct binding, in vitro and in vivo functional rescue; single lab\",\n      \"pmids\": [\"40694989\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PUM1 silencing in pancreatic cancer cells increases p27 (CDKN1B) expression and the amount of the p27-CDK2 complex, as shown by immunoprecipitation. PUM1 overexpression attenuates TRAIL-induced effects, while PUM1 silencing enhances autophagy activation and TRAIL sensitivity.\",\n      \"method\": \"siRNA knockdown; immunoprecipitation (p27-CDK2 complex); Western blot; proliferation and apoptosis assays; in vivo xenograft\",\n      \"journal\": \"Phytomedicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP showing p27-CDK2 complex change; single lab, indirect pathway evidence\",\n      \"pmids\": [\"31128486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PUM1 regulates macrophage polarization via the PUM1/Cripto-1 pathway: PUM1 negatively regulates Cripto-1 expression and promotes M1-type macrophage polarization. Allogeneic blood transfusion inhibits ferroptosis in macrophages through effects on this pathway.\",\n      \"method\": \"RT-qPCR; Western blot; in vivo mouse model; in vitro RAW264.7 cell experiments; macrophage polarization marker analysis; JC-1 staining\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, primarily expression-level evidence with no direct binding or epistasis for PUM1-Cripto-1 mechanism\",\n      \"pmids\": [\"37387538\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PUM1 depletion mildly increases intracellular SARS-CoV-2 viral RNA levels, suggesting a mild antiviral or host-factor regulatory role. PUM1 also negatively regulates innate immunity gene expression both at steady state and during SARS-CoV-2 infection. However, altering PUM1 levels does not affect progeny virion production.\",\n      \"method\": \"siRNA/shRNA depletion; viral RNA quantification; innate immunity gene expression assays; progeny virion production assays (plaque/TCID50)\",\n      \"journal\": \"The Journal of general virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with quantitative viral and immune gene readouts; negative result for virion production explicitly noted; single lab\",\n      \"pmids\": [\"40956600\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PUM1 is a sequence-specific RNA-binding protein that recognizes the consensus motif UGUAHAUA in 3' UTRs of target mRNAs to repress their stability and/or translation via recruitment of the CCR4-NOT deadenylase complex (modulated by phosphorylation and PABPC availability); validated targets include CDKN1B/p27 (controlling cell proliferation and body size), TLR4 (regulating NF-κB-mediated cellular aging), LGP2 (suppressing innate immunity in a two-phase cascade), γ-globin HBG1 (mediating hemoglobin switching), KCNK3 (driven by HIF1α in pulmonary hypertension), HOTAIR lncRNA (restricting trophoblast invasion), DEPTOR (activating PI3K-Akt glycolysis), and PAK6 (conferring ferroptosis resistance), with PUM1's activity modulated by cofactors such as NANOS proteins and tuned by phosphorylation of its intrinsically disordered regions.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PUM1 is a sequence-specific RNA-binding protein that recognizes a UGUAHAUA consensus motif in the 3' UTRs of target mRNAs and acts as a dose-sensitive post-transcriptional repressor controlling cell proliferation, innate immunity, and development [#0, #1]. Mechanistically, PUM1 destabilizes bound transcripts by recruiting the CCR4-NOT deadenylase complex (not the PAN deadenylase) in a poly(A)-tail-dependent manner, and its repressive output is continuously tunable: phosphorylation within PUM1's intrinsically disordered regions graded­ly modulates multivalent CCR4-NOT binding, and rising PABPC1/PABPC4 concentrations protect the poly(A) tail to dampen PUM1 activity [#18, #19]. PUM1 can also repress targets at the translational level without altering mRNA abundance, as shown for CDKN1B/p27, and can cooperate with NANOS cofactors to confer target specificity [#10, #11, #13]. Through CDKN1B/p27 repression PUM1 promotes the G1-S transition and controls postnatal growth, a relationship established by genetic epistasis in which Cdkn1b loss rescues Pum1-null growth defects [#2]. Beyond proliferation, PUM1 restrains innate immunity by repressing LGP2 to suppress a two-phase interferon cascade [#4], suppresses TLR4-NF-\\u03baB signaling to protect against oxidative senescence [#5], and represses \\u03b3-globin (HBG1) to drive fetal-to-adult hemoglobin switching during erythroid differentiation [#7]. PUM1 expression is itself regulated by upstream factors including KLF1 in erythroid cells and HIF1\\u03b1 under hypoxia [#7, #17]. PUM1 haploinsufficiency, through reduced protein levels that correlate with phenotypic severity, causes a dose-dependent neurological disorder [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Established the founding biochemical identity of human PUM1: what sequence it recognizes and what it does to bound transcripts.\",\n      \"evidence\": \"Genome-wide RIP-microarray plus knockdown mRNA-stability assays and stress granule immunofluorescence\",\n      \"pmids\": [\"18411299\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve the deadenylase machinery used for decay\", \"Translational repression inferred from localization, not directly measured\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected PUM1 to a defined proliferative output by showing it represses CDKN1B/p27 and that this relationship is genetically epistatic for growth control.\",\n      \"evidence\": \"Pum1/Pum2 knockout mice, 3' UTR reporters, and Pum1-/- x Cdkn1b-/- double-mutant rescue\",\n      \"pmids\": [\"30811992\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not separate translational vs decay contributions at CDKN1B in vivo\", \"Tissue specificity of the epistasis not fully mapped\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined PUM1 as a negative regulator of innate immunity by placing LGP2 as the direct downstream mediator of a two-phase interferon cascade, distinguishing PUM1 from PUM2.\",\n      \"evidence\": \"Combinatorial siRNA epistasis (PUM1+LGP2), interferon functional assays, HSV-1 replication, PUM2 negative control\",\n      \"pmids\": [\"28760986\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct PUM1 binding to LGP2 3' UTR not biochemically shown in this study\", \"Physiological trigger that relieves PUM1 repression unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Established PUM1 as a dose-sensitive repressor whose protein level quantitatively determines phenotypic severity, linking it to human disease.\",\n      \"evidence\": \"Patient-derived cells with quantitative protein/target measurements and dose-response correlation across patients\",\n      \"pmids\": [\"29474920\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which neuronal targets drive each phenotype not fully resolved\", \"Molecular basis of missense-induced protein destabilization not characterized\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Showed PUM1 controls a discrete decay regulon coupled to DNA damage, defining a context where PUM1 abundance is itself regulated to alter target stability.\",\n      \"evidence\": \"Transcriptome-wide stability profiling plus RIP-seq, with cisplatin sensitivity and DNA synthesis assays\",\n      \"pmids\": [\"32375027\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism reducing PUM1 abundance after DNA damage unresolved\", \"Direct binding to all 48 targets not individually validated\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrated PUM1 represses HBG1 to govern hemoglobin switching and is transcriptionally driven by KLF1, embedding it in erythroid gene regulation.\",\n      \"evidence\": \"RIP, mRNA stability and translational efficiency assays, erythroid knockdown, plus a patient with an RNA-binding-domain mutation and elevated HbF\",\n      \"pmids\": [\"35667093\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative weight of decay vs translational repression at HBG1 not quantified\", \"Whether HbF derepression is therapeutically tractable not addressed\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked PUM1 to TLR4-NF-\\u03baB-driven cellular senescence, defining a protective post-transcriptional axis confirmed in disease models.\",\n      \"evidence\": \"RIP and 3' UTR binding, bidirectional manipulation with NF-\\u03baB readouts, and in vivo osteoarthritis gene therapy\",\n      \"pmids\": [\"35034101\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether repression is translational or decay-based at TLR4 not dissected\", \"Upstream control of PUM1 in senescence unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Revealed that PUM1 specificity and cofactor cooperation diverge from PUM2, including PBE-independent repression and NANOS3 partnership.\",\n      \"evidence\": \"Reporter assays with PBE-mutant 3' UTRs, EMSA, and NANOS paralog co-repression assays\",\n      \"pmids\": [\"30269240\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of PBE-independent binding not defined\", \"Single target (SIAH1) and single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Showed PUM1 and PUM2 build distinct RNP networks with different cofactors and target pools, formalizing paralog functional divergence.\",\n      \"evidence\": \"RIP-seq, RNA-seq, and mass spectrometry interactome in TCam-2 germ cells\",\n      \"pmids\": [\"32316190\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single cell model limits generality\", \"Functional consequences of distinct cofactor sets not tested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided the structural-biochemical basis for how PUM1 recruits CCR4-NOT and how phosphorylation tunes deadenylation in a graded manner.\",\n      \"evidence\": \"Structural biology and reconstituted in vitro deadenylation with phosphomimetic/phosphoablative IDR variants (preprint)\",\n      \"pmids\": [\"bio_10.1101_2024.10.18.618793\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Kinases responsible for PUM1 IDR phosphorylation in vivo not identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined the deadenylase requirement and PABPC-based tunability of PUM1-mediated decay, completing the core repression mechanism.\",\n      \"evidence\": \"Biochemical reconstitution, deadenylase-requirement assays, PABPC co-IP and titration (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.10.02.680050\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Whether PABPC tuning operates at endogenous targets in cells not shown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Expanded the regulatory hierarchy by showing HIF1\\u03b1 transcriptionally induces PUM1 to destabilize KCNK3 in pulmonary hypertension.\",\n      \"evidence\": \"ChIP for HIF1\\u03b1-promoter binding, RIP, mRNA stability assays, and AAV9 in vivo knockdown in rat PH models\",\n      \"pmids\": [\"41135634\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Translational vs decay contribution at KCNK3 not separated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed PUM1 can stabilize rather than degrade certain targets (DEPTOR), revealing context-dependent positive regulation feeding into PI3K-Akt/glycolysis.\",\n      \"evidence\": \"RIP, RNA-seq, metabolomics, and in vitro/in vivo knockdown in gastric cancer\",\n      \"pmids\": [\"37469018\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which PUM1 stabilizes (vs destabilizes) DEPTOR unresolved\", \"Single lab and cancer-specific context\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PUM1 switches between destabilizing and stabilizing target mRNAs, and which upstream kinases set its phosphorylation-dependent activity in specific cell types, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model reconciling decay (e.g. HBG1, KCNK3) vs stabilization (DEPTOR, PAK6) outcomes\", \"Kinases and signals controlling PUM1 IDR phosphorylation in vivo unidentified\", \"In-cell validation of PABPC tunability still pending peer review\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 5, 7, 9, 14, 17, 20]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [0, 6, 18]},\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [2, 10]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [18, 19]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 6, 18, 19]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [4, 5, 23]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2, 13]}\n    ],\n    \"complexes\": [\"CCR4-NOT deadenylase complex\", \"NANOS3-PUM1 repressor complex\"],\n    \"partners\": [\"NANOS3\", \"PABPC1\", \"PABPC4\", \"PUM2\", \"DDX5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}