{"gene":"CSDE1","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2016,"finding":"CSDE1/UNR controls pro-metastatic targets VIM and RAC1 at the level of mRNA steady-state and translation elongation/termination in melanoma cells, as identified by iCLIP sequencing, RNA sequencing, and ribosome profiling combined with loss- and gain-of-function studies.","method":"iCLIP-seq, RNA-seq, ribosome profiling, loss- and gain-of-function experiments","journal":"Cancer cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal high-throughput methods combined with functional validation in the same study, replicated mechanistic targets across subsequent papers","pmids":["27908735"],"is_preprint":false},{"year":2017,"finding":"CSDE1 post-transcriptionally regulates core components of hESC identity, neuroectoderm commitment, and neurogenesis, including binding FABP7 and VIM mRNAs to regulate their stability and translation, thereby maintaining the undifferentiated hESC state and preventing default neural fate.","method":"RNA-binding assays, loss-of-function (CSDE1 knockdown/overexpression), transcriptomic analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal functional experiments (KD and OE) with transcriptomic readout and direct RNA-binding validation, replicated VIM as a target from prior melanoma study","pmids":["29129916"],"is_preprint":false},{"year":2019,"finding":"CSDE1 loss-of-function in primary mouse cortical neurons causes neurite overgrowth, abnormal dendritic spine morphology, impaired synapse formation, and impaired synaptic transmission; HITS-CLIP showed Csde1 binds targets enriched in neuronal development and synaptic plasticity pathways including FMRP targets.","method":"shRNA knockdown in primary cortical neurons, HITS-CLIP, Drosophila knockdown and mutant experiments","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct KD with defined cellular phenotypes in both mouse neurons and Drosophila, HITS-CLIP for binding targets, multiple orthogonal methods","pmids":["31579823"],"is_preprint":false},{"year":2022,"finding":"CSDE1 promotes oncogene-induced senescence (OIS) in primary mouse keratinocytes by two independent mechanisms: enhancing mRNA stability of SASP factor transcripts and repressing YBX1 mRNA translation; CSDE1 depletion leads to senescence bypass, immortalization, and tumor formation (tumor suppressor role in this context).","method":"shRNA depletion of CSDE1, high-throughput transcriptomic and translation assays, YBX1 rescue experiments","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — unbiased high-throughput analyses with two mechanistically distinct pathways confirmed by rescue experiments, multiple orthogonal methods in one study","pmids":["35021076"],"is_preprint":false},{"year":2021,"finding":"CSDE1 interacts with AGO2 (the essential component of miRISC) in a manner facilitated by target mRNAs and dependent on the first cold shock domain of CSDE1; CSDE1 counteracts AGO2 binding at the 3'UTR of PMEPA1, attenuating miR-129-5p/AGO2-mediated silencing and elevating PMEPA1 expression in melanoma.","method":"Co-immunoprecipitation, RNA immunoprecipitation, functional reporter assays, domain mutagenesis","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, domain mutagenesis identifying CSD1, RNA-binding functional assays in single lab with multiple orthogonal methods","pmids":["33833398"],"is_preprint":false},{"year":2021,"finding":"CSDE1 promotes STAT1 dephosphorylation by stabilizing T cell protein tyrosine phosphatase (TCPTP), thereby reducing immunogenicity of tumor cells; SMYD3 mediates H3K4 trimethylation of the CSDE1 locus under mechanotransduction control, regulating CSDE1 expression.","method":"Protein interaction assays, phosphorylation assays, ChIP for H3K4me3 at CSDE1 locus, single tumor-repopulating cell tumor formation in mice","journal":"Science translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple assays (Co-IP for CSDE1-TCPTP, ChIP for SMYD3-CSDE1 locus) in single lab; abstract lacks full mechanistic detail","pmids":["36724242"],"is_preprint":false},{"year":2022,"finding":"TRIM28 acts as an E3 ligase for CSDE1 in HCC, promoting its degradation via the ubiquitin-proteasome pathway; lncRNA ARHGAP5-AS1 attenuates CSDE1-TRIM28 interaction, preventing CSDE1 degradation and allowing elevated CSDE1 to promote VIM and RAC1 translation and activate the ERK pathway.","method":"Co-immunoprecipitation, ubiquitination assays, RNA pulldown, functional cancer cell assays","journal":"Clinical and translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP identifying TRIM28 as E3 ligase and ARHGAP5-AS1 as competitor, multiple biochemical assays in single lab","pmids":["36354136"],"is_preprint":false},{"year":2021,"finding":"A point-mutated CSDE1P5S form inhibits VSV replication by disrupting viral transcription; wild-type CSDE1 is a major cellular co-factor for VSV replication, and CSDE1P5S generates a neo-epitope recognized by non-tolerized T cells.","method":"Mutant CSDE1 expression in tumor cells, viral replication assays, compensatory viral mutation analysis","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — specific point mutation with defined functional consequence on viral replication, single lab with multiple experimental validations","pmids":["33772027"],"is_preprint":false},{"year":2018,"finding":"CSDE1 binds transcripts involved in ribogenesis, mRNA translation, protein degradation, mitochondrial respiratory chain, and mitosis in erythroid cells; CRISPR/Cas9-mediated deletion of the first cold shock domain reduces CSDE1 function and affects RNA and protein expression of bound transcripts, including enhanced PABPC1 protein despite reduced PABPC1 mRNA (indicating post-transcriptional regulation).","method":"RNA immunoprecipitation-sequencing, CRISPR/Cas9 deletion of CSD1, RNA and protein expression analysis","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP-seq for binding targets plus CRISPR domain deletion with functional readout, single lab","pmids":["29422612"],"is_preprint":false},{"year":2018,"finding":"CSDE1 directly interacts with BC200 lncRNA; STRAP binds BC200 indirectly via heterodimerization with CSDE1; knockdown of CSDE1 and BC200 reveal a reciprocal regulatory relationship; BC200 knockdown causes dramatic reorganization of CSDE1 into distinct nuclear foci.","method":"Proteomic analysis of BC200 RNP, reciprocal Co-IP, RNA truncation mapping, immunofluorescence after BC200 knockdown","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct interaction confirmed by reciprocal Co-IP and RNA truncation mapping, localization change validated by immunofluorescence, single lab","pmids":["30247708"],"is_preprint":false},{"year":2018,"finding":"STRAP (Serine/Threonine kinase receptor-associated protein) is the protein most strongly associated with CSDE1 in erythroblasts; reduced STRAP expression alters mRNA and/or protein expression of several CSDE1-bound transcripts including Vim, Elavl1, Hmbs, eIF4g3, and Pabpc4, affecting ribosome function and cell cycle control.","method":"Co-immunoprecipitation, shRNA knockdown of STRAP, RNA-binding and expression analysis","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP identifying STRAP as primary CSDE1 partner in erythroblasts, functional KD with specific transcript readouts, single lab","pmids":["30138317"],"is_preprint":false},{"year":2013,"finding":"shRNA-mediated inhibition of Csde1 expression in mice causes failure of precerebellar neurons to complete their migration into prospective target regions, with neurons remaining in migratory paths and failing to invade the depth of the hindbrain via radial migration.","method":"shRNA knockdown in mouse, in vivo neuronal migration analysis","journal":"Neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo shRNA with specific neuronal migration phenotype, single lab","pmids":["24012837"],"is_preprint":false},{"year":2023,"finding":"CSDE1 binds ctnnb1 mRNAs (encoding β-catenin) and regulates their translation but not stability, thereby enhancing β-catenin protein levels and Wnt/β-catenin signaling activity to promote hematopoietic stem and progenitor cell generation during zebrafish development.","method":"Genetic mutants and morphants in zebrafish, RNA immunoprecipitation, protein and mRNA expression analysis","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function in zebrafish with RIP to validate direct ctnnb1 binding and translation vs. stability analysis, single lab","pmids":["37874038"],"is_preprint":false},{"year":2023,"finding":"CSDE1 promotes miR-451 biogenesis in erythroid cells by binding pre-miR-451, regulating AGO2 processing through its N-terminal domains, and interacting with PARN to promote trimming of intermediate miR-451 to mature length.","method":"RNA immunoprecipitation, in vitro cleavage assays, domain deletion/mutagenesis analysis","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding and in vitro processing assays with domain mapping, single lab","pmids":["37493604"],"is_preprint":false},{"year":2022,"finding":"CSDE1, phosphorylated C-terminal domain (p-CTD) of RNA polymerase II, and CDK7 form a complex in TNBC cells; CSDE1 downregulation weakens RNAPII p-CTD–CDK7 interaction, reducing RNAPII p-CTD expression and decreasing RAC1 transcription.","method":"Co-immunoprecipitation identifying CSDE1/RNAPII p-CTD/CDK7 complex, CSDE1 inhibition experiments with downstream signaling readouts","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP for ternary complex, functional knockdown with mechanistic pathway readout, single lab","pmids":["35490208"],"is_preprint":false},{"year":2022,"finding":"CSDE1 directly interacts with HIV-1 Gag and NCp7; interaction with Gag is RNA-dependent and mediated by the NC domain of Gag; CSDE1 acts as an IRES trans-acting factor (ITAF), increasing HIV-1 IRES-dependent translation; NCp7 counteracts CSDE1's stimulatory effect while Gag increases it.","method":"Co-immunoprecipitation, FRET-FLIM, dual luciferase IRES assay, CSDE1 knockdown in HeLa cells, IRES point mutations","journal":"Viruses","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and FRET-FLIM for interaction, functional IRES assay with IRES point mutations supporting mechanistic model, single lab","pmids":["36016420"],"is_preprint":false},{"year":2025,"finding":"The Csde1-Strap complex binds Bach2 mRNA to couple its mRNA decay with translation, restraining the magnitude and duration of Bach2 protein expression during B cell to plasma cell differentiation; absence of Csde1 or Strap decouples Bach2 translation from mRNA decay, causing elevated and prolonged Bach2 expression and impaired plasma cell differentiation.","method":"RNA interactome capture-coupled CRISPR/Cas9 screen, Co-IP for Csde1-Strap complex, RNA immunoprecipitation for Bach2 mRNA binding, mRNA decay and translation assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR functional screen, direct complex identification, RNA-binding validation, and mRNA decay/translation uncoupling assays with functional rescue, multiple orthogonal methods","pmids":["40133358"],"is_preprint":false},{"year":2025,"finding":"CSDE1 undergoes context-dependent phosphorylation during early cellular transformation in melanoma cells, which correlates with changes in subcellular localization and promotes increased interactions with ribosomes; melanoma cells show one major CSDE1 isoform with enhanced ribosome association compared to healthy melanocytes.","method":"Long-read Nanopore sequencing, 2D gel electrophoresis, transcriptome analysis, interactome analysis (ribosome co-IP), phosphorylation mapping","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (proteomics, sequencing, interactome) in single lab identifying phosphorylation-dependent ribosome interaction","pmids":["40883018"],"is_preprint":false},{"year":2025,"finding":"Csde1 directly binds the 3'UTR of Cdk6 mRNA to maintain its stability, thereby regulating CDK6 levels and controlling G1-to-S phase transition; Csde1 knockout in mice during cortical development causes prolonged G1 phase in neural progenitors, impaired proliferation, abnormal cortical lamination, and embryonic lethality.","method":"Csde1 conditional knockout in mice, CLIP-seq for 3'UTR binding, dual thymidine-labelling for cell cycle analysis, transcriptomic analysis","journal":"Neuroscience bulletin","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KO with specific phenotype plus CLIP-seq identifying Cdk6 3'UTR binding and mRNA stability readout, single lab","pmids":["40555862"],"is_preprint":false},{"year":2025,"finding":"CSDE1 forms RNA-dependent biomolecular condensates (liquid-liquid phase separation) that sequester immunostimulatory viral RNAs, shielding them from RIG-I-like receptor recognition; upon viral infection, TBK1 kinase phosphorylates CSDE1, leading to condensate disassembly and relief of immune suppression; CSDE1-knockout mice show increased resistance to viral infection and enhanced interferon production.","method":"CSDE1 KO macrophages and mice, LLPS assays, TBK1 phosphorylation assays, interferon measurement, small molecule condensate disruption","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO mice with viral resistance phenotype, LLPS assays, TBK1-dependent phosphorylation mechanism, multiple orthogonal methods in single study","pmids":["42049720"],"is_preprint":false},{"year":2025,"finding":"CSDE1 forms a ternary complex with eIF3a (protein) and RPA2 mRNA, promoting RPA2 expression and enhancing nucleotide excision repair (NER) and homologous recombination (HR) DNA repair pathways; systemic CSDE1 knockout in mice increases DNA damage following X-ray irradiation or bleomycin treatment; CSDE1 also inhibits the cGAS-STING pathway through RPA2.","method":"Biotin pulldown, EMSA, Co-IP for CSDE1-eIF3a-RPA2 ternary complex, CSDE1 knockout mouse model, comet assay, immunofluorescence","journal":"Drug resistance updates","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple biochemical assays (pulldown, EMSA, Co-IP) plus KO mouse model with functional readouts, single lab","pmids":["40398074"],"is_preprint":false},{"year":2025,"finding":"CSDE1 stabilizes AGO2 protein in mouse embryonic stem cells by preventing its ubiquitination; CSDE1 also stabilizes pluripotency factors NANOG, SOX2, and OCT4 through the same anti-ubiquitination mechanism; the N-terminal CSD1 domain is required for CSDE1-AGO2 interaction and AGO2 stabilization.","method":"Co-immunoprecipitation, ubiquitination assays, domain deletion (CSD1 mutant), Western blotting for pluripotency markers","journal":"Frontiers in molecular biosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, ubiquitination assays, and domain mutagenesis in single lab establishing post-translational stabilization mechanism","pmids":["41624769"],"is_preprint":false},{"year":2026,"finding":"MKRN2 E3 ubiquitin ligase directly ubiquitinates CSDE1 at four lysine residues (K81, K91, K208, K727); MKRN2 and CSDE1 form co-localized condensates via liquid-liquid phase separation; disruption of either protein abolishes condensate formation; MKRN2 KO mice display autism-spectrum-like social behavior abnormalities.","method":"Mass spectrometry screening for MKRN2 substrates, ubiquitination mutagenesis at identified lysine residues, LLPS assays in HEK293/SH-SY5Y cells, Mkrn2-knockout mouse behavioral assays","journal":"Frontiers in cellular neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS-identified substrate with mutagenesis of ubiquitination sites, LLPS assays, and in vivo KO model, single lab","pmids":["41757349"],"is_preprint":false},{"year":2026,"finding":"MKRN3 (an E3 ubiquitin ligase) ubiquitinates CSDE1 as a major substrate in ovarian cancer cells, promoting CSDE1 proteolytic degradation and suppressing cancer cell proliferation.","method":"Mass spectrometry-based proteomics screens, ubiquitination assays, in vitro and in vivo proliferation assays with MKRN3 restoration","journal":"Oncogenesis","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS identification of CSDE1 as MKRN3 substrate with functional validation in cell and animal models, single lab","pmids":["42204155"],"is_preprint":false},{"year":2026,"finding":"CSDE1 directly binds IL-6 mRNA and negatively regulates its stability, thereby restraining IL-6 expression in endometrial cancer cells; loss of CSDE1 increases IL-6 mRNA stability and promotes malignant transformation.","method":"RNA immunoprecipitation, mRNA stability assays (CSDE1 KO vs. WT), IL-6 shRNA rescue, pharmacological IL-6 inhibition rescue","journal":"Cell communication and signaling : CCS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RIP for IL-6 mRNA binding and mRNA stability assays with CRISPR KO plus functional rescue experiments, single lab","pmids":["42177550"],"is_preprint":false},{"year":2026,"finding":"CSDE1 enhances LDHA mRNA stability, leading to increased glycolytic activity and lactate production in gastric cancer, which then promotes HOXD9 transcription through H3K18 lactylation.","method":"RNA immunoprecipitation for CSDE1-LDHA mRNA interaction, chromatin immunoprecipitation for H3K18 lactylation at HOXD9 promoter, glycolytic assays, in vivo xenograft experiments","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP for direct LDHA mRNA binding, ChIP for downstream epigenetic modification, functional in vitro and in vivo assays, single lab","pmids":["41864431"],"is_preprint":false},{"year":2026,"finding":"CSDE1 promotes passenger strand cleavage of miR-486 by facilitating AGO2-dependent removal of the passenger strand miR-486-3p; loss of CSDE1 increases miR-486-3p levels and decreases in vitro cleavage efficiency; the N-terminal CSD1 domain is required for CSDE1-AGO2 interaction and this function.","method":"In vitro cleavage assays, CSDE1 KO in leukemia cells, CSD1 domain deletion, miRNA sequencing","journal":"RNA biology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro cleavage reconstitution plus cell-based KO with specific miRNA quantification and domain mutagenesis, single lab","pmids":["41905768"],"is_preprint":false},{"year":2026,"finding":"CSDE1 associates with TOM20 (outer mitochondrial membrane import receptor) via its N-terminal region in an RNA-independent manner in sensory neurons; CSDE1 also associates with nuclear-encoded mitochondrial mRNAs enriched for inner membrane/matrix and oxidative phosphorylation pathways; CSDE1 depletion reduces mitochondrial-fraction abundance of electron transport chain mRNAs and selected mitochondrial proteins.","method":"CSDE1 immunoprecipitation-sequencing from dorsal root ganglion tissue, Co-IP for TOM20 interaction, N-terminal deletion for RNA-independent binding, subcellular fractionation","journal":"Antioxidants (Basel, Switzerland)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP-seq in native tissue, Co-IP with domain mapping for TOM20 interaction, fractionation to show functional consequence, single lab","pmids":["42193230"],"is_preprint":false},{"year":2025,"finding":"CSDE1 and PABPC1 form a complex that caps coronavirus poly(A) tails, slowing their shortening (deadenylation) and protecting viral mRNA stability during infection.","method":"Biochemical complex identification, poly(A)-tail length profiling during coronavirus infection","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint with complex identification but limited mechanistic detail in abstract; single lab, methods not fully described in abstract","pmids":[],"is_preprint":true}],"current_model":"CSDE1 is a multi-domain RNA-binding protein (containing cold shock domains, with CSD1 being critical for AGO2 and partner interactions) that post-transcriptionally regulates target mRNA stability and translation in a context-dependent manner: it coordinates RNA regulons controlling cell identity, differentiation, and oncogenesis (promoting translation of VIM, RAC1, LDHA and stability of other targets in cancer contexts while repressing YBX1 translation and stabilizing SASP mRNAs during senescence), interacts with key protein partners including AGO2/miRISC (attenuating miRNA-mediated silencing of specific targets and promoting miR-451/miR-486 biogenesis), STRAP/UNRIP (together regulating mRNA decay coupled to translation), eIF3a (forming ternary complexes on specific mRNAs like RPA2), and TOM20 (localizing to mitochondria to regulate mitochondrial mRNAs); undergoes phosphorylation (by TBK1 during viral infection, and during early melanoma transformation) that modulates its subcellular localization, ribosome interactions, and condensate dynamics; forms liquid-liquid phase separation condensates that sequester viral RNAs from innate immune sensing; and is subject to ubiquitin-proteasome degradation mediated by E3 ligases TRIM28, MKRN2, and MKRN3, with its stability protected in some contexts by lncRNA partners."},"narrative":{"mechanistic_narrative":"CSDE1 (UNR) is a multi-domain, cold shock domain-containing RNA-binding protein that organizes post-transcriptional RNA regulons governing cell identity, differentiation, and oncogenesis by binding defined target mRNAs and controlling their stability and translation in a context-dependent manner [PMID:27908735, PMID:29129916, PMID:40133358]. In cancer it acts predominantly as a pro-tumorigenic effector, driving the steady-state and translational output of pro-metastatic targets including VIM and RAC1 [PMID:27908735, PMID:36354136], stabilizing LDHA mRNA to fuel glycolysis and downstream H3K18-lactylation-driven transcription [PMID:41864431], and reducing tumor immunogenicity by stabilizing TCPTP to promote STAT1 dephosphorylation [PMID:36724242]; in other settings it is tumor-suppressive, enforcing oncogene-induced senescence by stabilizing SASP transcripts and repressing YBX1 translation [PMID:35021076], and restraining IL-6 mRNA stability in endometrial cancer [PMID:42177550]. CSDE1 controls developmental programs across systems—maintaining the undifferentiated hESC state and biasing against default neural fate [PMID:29129916], directing precerebellar and cortical neuron migration, proliferation, and synapse formation through targets including FABP7 and the Cdk6 3'UTR [PMID:31579823, PMID:24012837, PMID:40555862], and promoting hematopoietic stem/progenitor generation by enhancing ctnnb1/β-catenin translation [PMID:37874038]. Mechanistically it works through its N-terminal first cold shock domain (CSD1), which mediates interaction with AGO2 to attenuate or redirect miRISC activity: it shields specific 3'UTRs (e.g. PMEPA1) from miRNA silencing [PMID:33833398], stabilizes AGO2 and pluripotency factors against ubiquitination [PMID:41624769], and promotes miR-451/miR-486 biogenesis via AGO2-dependent processing and PARN trimming [PMID:37493604, PMID:41905768]. CSDE1 partners with STRAP/UNRIP to couple mRNA decay to translation, for example restraining Bach2 expression during plasma cell differentiation [PMID:30138317, PMID:40133358], forms ternary complexes with eIF3a on RPA2 mRNA to support DNA repair and dampen cGAS-STING signaling [PMID:40398074], and associates with TOM20 to localize and regulate mitochondrial mRNAs [PMID:42193230]. CSDE1 undergoes regulated phosphorylation that alters its localization, ribosome association, and condensate behavior—including TBK1-mediated phosphorylation that disassembles RNA-dependent phase-separated condensates which otherwise sequester viral RNA from RIG-I-like receptors [PMID:42049720, PMID:40883018]—and its abundance is set by E3 ligases TRIM28, MKRN2, and MKRN3 that target it for ubiquitin-proteasome degradation [PMID:36354136, PMID:41757349, PMID:42204155].","teleology":[{"year":2013,"claim":"Establishing whether CSDE1 has an in vivo developmental role, the first loss-of-function study showed it is required for neuronal migration, framing it as a regulator of nervous system development rather than a generic RNA-binding factor.","evidence":"shRNA knockdown in mouse with in vivo precerebellar neuron migration analysis","pmids":["24012837"],"confidence":"Medium","gaps":["No RNA targets identified","Migration defect not linked to specific bound transcripts"]},{"year":2016,"claim":"To define how CSDE1 acts molecularly in cancer, multi-omic mapping demonstrated it binds and controls pro-metastatic mRNAs VIM and RAC1 at both stability and translation, establishing CSDE1 as a sequence-specific post-transcriptional driver of metastasis.","evidence":"iCLIP-seq, RNA-seq, ribosome profiling, and gain/loss-of-function in melanoma cells","pmids":["27908735"],"confidence":"High","gaps":["Domain requirements for target selection not resolved","Upstream regulators of CSDE1 activity unknown"]},{"year":2017,"claim":"Asking whether CSDE1 governs cell fate decisions, work in hESCs showed it maintains the undifferentiated state and prevents default neural commitment via targets including FABP7 and VIM, generalizing its regulon concept to cell-identity control.","evidence":"RNA-binding assays and reciprocal knockdown/overexpression with transcriptomics in hESCs","pmids":["29129916"],"confidence":"High","gaps":["Mechanism distinguishing stability vs. translation control per target not resolved","Partner proteins not defined"]},{"year":2018,"claim":"To identify the protein machinery CSDE1 works with and its target classes, erythroid studies identified STRAP/UNRIP as its dominant partner, BC200 lncRNA as a direct binder controlling its localization, and CSD1 as functionally essential, anchoring a partner-and-domain framework.","evidence":"RIP-seq, reciprocal Co-IP, RNA truncation mapping, CRISPR CSD1 deletion, and immunofluorescence in erythroblasts","pmids":["29422612","30247708","30138317"],"confidence":"Medium","gaps":["Biochemical mechanism of STRAP-CSDE1 cooperation not defined","How BC200 reorganizes CSDE1 foci unknown"]},{"year":2019,"claim":"Extending the neuronal role mechanistically, HITS-CLIP and knockdown showed CSDE1 binds neuronal development/synaptic plasticity transcripts and controls neurite, spine, and synapse formation, linking its RNA targets to specific neuronal phenotypes.","evidence":"shRNA knockdown in primary cortical neurons, HITS-CLIP, and Drosophila genetics","pmids":["31579823"],"confidence":"High","gaps":["Individual causative target mRNAs for each phenotype not isolated","Relationship to FMRP target overlap not mechanistically resolved"]},{"year":2021,"claim":"Resolving how CSDE1 intersects with miRNA silencing, it was shown to bind AGO2 via CSD1 in a target-mRNA-facilitated manner and counteract miRISC at specific 3'UTRs, defining a mechanism by which it derepresses chosen targets like PMEPA1.","evidence":"Reciprocal Co-IP, RIP, domain mutagenesis, and reporter assays in melanoma","pmids":["33833398"],"confidence":"High","gaps":["Generality of AGO2 antagonism across targets unknown","Structural basis of CSD1-AGO2 contact not determined"]},{"year":2021,"claim":"Broadening CSDE1's reach beyond mRNA fate, studies revealed it stabilizes TCPTP to dampen tumor immunogenicity and that it is itself a host co-factor for VSV replication whose point mutant generates a T-cell neo-epitope, implicating it in immune evasion and viral biology.","evidence":"Protein interaction/phosphorylation assays, ChIP, single-cell tumor formation, and mutant CSDE1 viral replication assays","pmids":["36724242","33772027"],"confidence":"Medium","gaps":["Mechanism of TCPTP stabilization not detailed","How wild-type CSDE1 supports VSV transcription unresolved"]},{"year":2022,"claim":"Determining how CSDE1 abundance is set and how it can be oncogenic, work identified TRIM28 as an E3 ligase degrading CSDE1 (antagonized by lncRNA ARHGAP5-AS1) and placed CSDE1 in an RNAPII p-CTD/CDK7 complex driving RAC1 transcription, while a separate study showed it enforces senescence as a tumor suppressor.","evidence":"Co-IP, ubiquitination and RNA pulldown assays in HCC, ternary complex Co-IP in TNBC, and shRNA depletion with rescue in keratinocytes","pmids":["36354136","35490208","35021076"],"confidence":"High","gaps":["What dictates pro-tumor vs. tumor-suppressor outcome is unresolved","Stoichiometry of the RNAPII p-CTD/CDK7 complex unknown"]},{"year":2023,"claim":"Refining CSDE1's role in miRNA biogenesis and developmental signaling, it was shown to promote miR-451 maturation by directing AGO2 processing and PARN trimming, and to enhance β-catenin translation to support hematopoietic stem/progenitor cell generation.","evidence":"RIP, in vitro cleavage assays, domain mutagenesis in erythroid cells, and zebrafish genetics with RIP for ctnnb1","pmids":["37493604","37874038"],"confidence":"Medium","gaps":["How CSDE1 switches between miRNA biogenesis and silencing-antagonist roles unknown","Direct biochemical role in PARN recruitment not fully defined"]},{"year":2025,"claim":"Integrating CSDE1's regulatory logic and biophysics, studies established the Csde1-Strap complex couples Bach2 mRNA decay to translation during plasma cell differentiation, defined a TBK1-phosphorylation-controlled condensate that sequesters viral RNA from RLRs, showed eIF3a/RPA2 ternary complexes support DNA repair, and demonstrated phosphorylation-dependent ribosome association during transformation.","evidence":"RNA-interactome CRISPR screen with decay/translation assays, KO mice with LLPS and TBK1 phosphorylation assays, biotin pulldown/EMSA/Co-IP with KO mouse repair assays, and Nanopore/2D-gel/interactome proteomics","pmids":["40133358","42049720","40398074","40883018"],"confidence":"High","gaps":["Phosphosites and kinases governing each context not unified","Determinants of condensate composition beyond viral RNA unclear"]},{"year":2026,"claim":"Expanding CSDE1's interactome and regulation, recent work showed it stabilizes AGO2 and pluripotency factors against ubiquitination via CSD1, promotes miR-486 passenger-strand cleavage, controls Cdk6, LDHA, and IL-6 mRNAs across cancers, localizes to mitochondria via TOM20, and is degraded by E3 ligases MKRN2 (forming co-condensates) and MKRN3.","evidence":"Co-IP/ubiquitination/domain-deletion assays, in vitro cleavage with KO and miRNA-seq, CLIP-seq and RIP with stability assays, TOM20 Co-IP with fractionation, and MS-based substrate screens with LLPS and KO models","pmids":["41624769","41905768","40555862","41864431","42177550","42193230","41757349","42204155"],"confidence":"Medium","gaps":["Whether ubiquitination sites overlap across MKRN2/MKRN3/TRIM28 unknown","Functional consequence of mitochondrial mRNA regulation in disease unclear","How phase separation integrates with degradation not resolved"]},{"year":null,"claim":"It remains unresolved what molecular features determine whether CSDE1 stabilizes versus destabilizes a given mRNA and whether it acts as an oncogene or tumor suppressor in a particular cellular context.","evidence":"Not addressed by the available corpus","pmids":[],"confidence":"Low","gaps":["No unifying rule for stability vs. translation control","No structural model of CSDE1 engaging targets with AGO2/eIF3a/STRAP","Context-determining cofactors and modifications not mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,1,4,8,12,18,24,25,27]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[0,12,15,16,17]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[13,26]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,21]},{"term_id":"GO:0140313","term_label":"molecular sequestering activity","supporting_discovery_ids":[19]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,17]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[9]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[27]},{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[17]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,13,16,26]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[0,6,24,25]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,2,11,12,18]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[5,16,19]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[20]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[6,21,22,23]}],"complexes":["CSDE1-STRAP complex","CSDE1-eIF3a-RPA2 ternary complex","CSDE1-RNAPII p-CTD-CDK7 complex"],"partners":["AGO2","STRAP","EIF3A","TRIM28","MKRN2","MKRN3","TOM20","PABPC1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O75534","full_name":"Cold shock domain-containing protein E1","aliases":["N-ras upstream gene protein","Protein UNR"],"length_aa":798,"mass_kda":88.9,"function":"RNA-binding protein involved in translationally coupled mRNA turnover (PubMed:11051545, PubMed:15314026). Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain (PubMed:11051545, PubMed:15314026). Required for efficient formation of stress granules (PubMed:29395067) (Microbial infection) Required for internal initiation of translation of human rhinovirus RNA","subcellular_location":"Cytoplasm; Cytoplasm, Stress granule; Cytoplasm, P-body","url":"https://www.uniprot.org/uniprotkb/O75534/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CSDE1","classification":"Not Classified","n_dependent_lines":309,"n_total_lines":1208,"dependency_fraction":0.25579470198675497},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPZB","stoichiometry":0.2},{"gene":"LSM14B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CSDE1","total_profiled":1310},"omim":[{"mim_id":"605986","title":"SERINE/THREONINE KINASE RECEPTOR-ASSOCIATED PROTEIN; STRAP","url":"https://www.omim.org/entry/605986"},{"mim_id":"191510","title":"COLD-SHOCK DOMAIN-CONTAINING E1, RNA-BINDING; CSDE1","url":"https://www.omim.org/entry/191510"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"Endoplasmic reticulum","reliability":"Additional"},{"location":"Golgi apparatus","reliability":"Additional"},{"location":"Plasma membrane","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"skeletal muscle","ntpm":1250.0}],"url":"https://www.proteinatlas.org/search/CSDE1"},"hgnc":{"alias_symbol":["D1S155E","UNR"],"prev_symbol":[]},"alphafold":{"accession":"O75534","domains":[{"cath_id":"2.40.50.140","chopping":"24-88","consensus_level":"high","plddt":86.1782,"start":24,"end":88},{"cath_id":"2.40.50.140","chopping":"98-109_123-179","consensus_level":"medium","plddt":85.503,"start":98,"end":179},{"cath_id":"2.40.50.140","chopping":"184-246","consensus_level":"medium","plddt":92.2856,"start":184,"end":246},{"cath_id":"2.40.50.140","chopping":"255-341","consensus_level":"medium","plddt":89.2355,"start":255,"end":341},{"cath_id":"2.40.50.140","chopping":"347-411","consensus_level":"medium","plddt":88.0488,"start":347,"end":411},{"cath_id":"2.40.50.140","chopping":"426-439_455-510","consensus_level":"medium","plddt":75.7353,"start":426,"end":510},{"cath_id":"2.40.50.140","chopping":"518-580","consensus_level":"medium","plddt":82.7027,"start":518,"end":580},{"cath_id":"2.40.50.140","chopping":"591-671","consensus_level":"high","plddt":84.8858,"start":591,"end":671},{"cath_id":"2.40.50.140","chopping":"675-738","consensus_level":"high","plddt":85.342,"start":675,"end":738}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O75534","model_url":"https://alphafold.ebi.ac.uk/files/AF-O75534-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O75534-F1-predicted_aligned_error_v6.png","plddt_mean":79.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CSDE1","jax_strain_url":"https://www.jax.org/strain/search?query=CSDE1"},"sequence":{"accession":"O75534","fasta_url":"https://rest.uniprot.org/uniprotkb/O75534.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O75534/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O75534"}},"corpus_meta":[{"pmid":"27908735","id":"PMC_27908735","title":"UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis.","date":"2016","source":"Cancer cell","url":"https://pubmed.ncbi.nlm.nih.gov/27908735","citation_count":127,"is_preprint":false},{"pmid":"29129916","id":"PMC_29129916","title":"A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29129916","citation_count":62,"is_preprint":false},{"pmid":"31987048","id":"PMC_31987048","title":"The role of CSDE1 in translational reprogramming and human diseases.","date":"2020","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/31987048","citation_count":51,"is_preprint":false},{"pmid":"36354136","id":"PMC_36354136","title":"N6 -methyladenosine-modified lncRNA ARHGAP5-AS1 stabilises CSDE1 and coordinates oncogenic RNA regulons in hepatocellular carcinoma.","date":"2022","source":"Clinical and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36354136","citation_count":40,"is_preprint":false},{"pmid":"31579823","id":"PMC_31579823","title":"Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission.","date":"2019","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/31579823","citation_count":38,"is_preprint":false},{"pmid":"31027221","id":"PMC_31027221","title":"UNR/CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition.","date":"2019","source":"Journal of clinical medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31027221","citation_count":32,"is_preprint":false},{"pmid":"36724242","id":"PMC_36724242","title":"Epigenetic modification of CSDE1 locus dictates immune recognition of nascent tumorigenic cells.","date":"2023","source":"Science translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36724242","citation_count":30,"is_preprint":false},{"pmid":"35021076","id":"PMC_35021076","title":"Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1.","date":"2022","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/35021076","citation_count":25,"is_preprint":false},{"pmid":"33772027","id":"PMC_33772027","title":"Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/33772027","citation_count":25,"is_preprint":false},{"pmid":"33833398","id":"PMC_33833398","title":"CSDE1 attenuates microRNA-mediated silencing of PMEPA1 in melanoma.","date":"2021","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/33833398","citation_count":21,"is_preprint":false},{"pmid":"24012837","id":"PMC_24012837","title":"The control of precerebellar neuron migration by RNA-binding protein Csde1.","date":"2013","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/24012837","citation_count":20,"is_preprint":false},{"pmid":"32808651","id":"PMC_32808651","title":"LINC00205 promotes malignancy in lung cancer by recruiting FUS and stabilizing CSDE1.","date":"2020","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/32808651","citation_count":20,"is_preprint":false},{"pmid":"29422612","id":"PMC_29422612","title":"Csde1 binds transcripts involved in protein homeostasis and controls their expression in an erythroid cell line.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29422612","citation_count":19,"is_preprint":false},{"pmid":"30247708","id":"PMC_30247708","title":"Comprehensive analysis of the BC200 ribonucleoprotein reveals a reciprocal regulatory function with CSDE1/UNR.","date":"2018","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/30247708","citation_count":19,"is_preprint":false},{"pmid":"33867523","id":"PMC_33867523","title":"Wnt/β-catenin pathway and cell adhesion deregulation in CSDE1-related intellectual disability and autism spectrum disorders.","date":"2021","source":"Molecular psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/33867523","citation_count":17,"is_preprint":false},{"pmid":"35490208","id":"PMC_35490208","title":"Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer.","date":"2022","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/35490208","citation_count":14,"is_preprint":false},{"pmid":"37493604","id":"PMC_37493604","title":"CSDE1 promotes miR-451 biogenesis.","date":"2023","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/37493604","citation_count":13,"is_preprint":false},{"pmid":"33662035","id":"PMC_33662035","title":"The CDT of Helicobacter hepaticus induces pro-survival autophagy and nucleoplasmic reticulum formation concentrating the RNA binding proteins UNR/CSDE1 and P62/SQSTM1.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/33662035","citation_count":12,"is_preprint":false},{"pmid":"30138317","id":"PMC_30138317","title":"Strap associates with Csde1 and affects expression of select Csde1-bound transcripts.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30138317","citation_count":11,"is_preprint":false},{"pmid":"32170829","id":"PMC_32170829","title":"Cold Shock Domain Containing E1 (CSDE1) Protein is Overexpressed and Can be Targeted to Inhibit Invasiveness in Pancreatic Cancer Cells.","date":"2020","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/32170829","citation_count":9,"is_preprint":false},{"pmid":"31938190","id":"PMC_31938190","title":"miR-132 and miR-212 cluster function as a tumor suppressor in thyroid cancer cells by CSDE1 mediated post-transcriptional program.","date":"2018","source":"International journal of clinical and experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/31938190","citation_count":8,"is_preprint":false},{"pmid":"34519148","id":"PMC_34519148","title":"A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents.","date":"2021","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/34519148","citation_count":6,"is_preprint":false},{"pmid":"37874038","id":"PMC_37874038","title":"The RNA-binding protein CSDE1 promotes hematopoietic stem and progenitor cell generation via translational control of Wnt signaling.","date":"2023","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/37874038","citation_count":4,"is_preprint":false},{"pmid":"35026469","id":"PMC_35026469","title":"A de novo truncating variant in CSDE1 in an adult-onset neuropsychiatric phenotype without intellectual disability.","date":"2022","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35026469","citation_count":4,"is_preprint":false},{"pmid":"39341378","id":"PMC_39341378","title":"Leader RNA facilitates snakehead vesiculovirus (SHVV) replication by interacting with CSDE1 and hnRNP A3.","date":"2024","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/39341378","citation_count":3,"is_preprint":false},{"pmid":"36016420","id":"PMC_36016420","title":"Upstream of N-Ras (Unr/CSDE1) Interacts with NCp7 and Gag, Modulating HIV-1 IRES-Mediated Translation Initiation.","date":"2022","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/36016420","citation_count":3,"is_preprint":false},{"pmid":"40133358","id":"PMC_40133358","title":"A Csde1-Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40133358","citation_count":2,"is_preprint":false},{"pmid":"23418499","id":"PMC_23418499","title":"Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23418499","citation_count":2,"is_preprint":false},{"pmid":"40555862","id":"PMC_40555862","title":"Csde1 Mediates Neurogenesis via Post-transcriptional Regulation of the Cell Cycle.","date":"2025","source":"Neuroscience bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/40555862","citation_count":1,"is_preprint":false},{"pmid":"41093770","id":"PMC_41093770","title":"CSDE1 regulates the miR-20a-5p/TMBIM6 axis in melanoma.","date":"2025","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/41093770","citation_count":1,"is_preprint":false},{"pmid":"40398074","id":"PMC_40398074","title":"CSDE1 enhances genotoxic drug resistance in cancer by modulating RPA2 through CSDE1-eIF3a regulatory complex.","date":"2025","source":"Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/40398074","citation_count":0,"is_preprint":false},{"pmid":"40883018","id":"PMC_40883018","title":"Context-dependent phosphorylation of CSDE1 drives interactions with ribosomes.","date":"2025","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/40883018","citation_count":0,"is_preprint":false},{"pmid":"41353256","id":"PMC_41353256","title":"CSDE1 depletion inhibits tumor progression through enhancing B-cell infiltration in NSCLC.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/41353256","citation_count":0,"is_preprint":false},{"pmid":"41864431","id":"PMC_41864431","title":"CSDE1-mediated histone lactylation modification of the HOXD9 promoter promotes gastric cancer progression.","date":"2026","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41864431","citation_count":0,"is_preprint":false},{"pmid":"41808419","id":"PMC_41808419","title":"CSDE1 Drives Glycolysis and the Progression of Prostate Cancer Through RAC1-Dependent RAS/MAPK Activation.","date":"2026","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/41808419","citation_count":0,"is_preprint":false},{"pmid":"42049720","id":"PMC_42049720","title":"CSDE1 promotes viral immune evasion through RNA-dependent and phosphorylation-modulated liquid-liquid phase separation.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/42049720","citation_count":0,"is_preprint":false},{"pmid":"42193230","id":"PMC_42193230","title":"CSDE1 Associates with TOM20 and Mitochondrial Protein-Encoding mRNAs in Sensory Neurons.","date":"2026","source":"Antioxidants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/42193230","citation_count":0,"is_preprint":false},{"pmid":"39291968","id":"PMC_39291968","title":"High-resolution RNA-sequencing reveals TRIM33 :: CSDE1 gene fusion in metastasizing vulvar melanoma.","date":"2024","source":"Melanoma research","url":"https://pubmed.ncbi.nlm.nih.gov/39291968","citation_count":0,"is_preprint":false},{"pmid":"41624769","id":"PMC_41624769","title":"CSDE1 stabilizes AGO2 in embryonic stem cells.","date":"2026","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/41624769","citation_count":0,"is_preprint":false},{"pmid":"42192424","id":"PMC_42192424","title":"CSDE1 in tumour immunology: spatiotemporal translational reprogramming and immune microenvironment remodeling.","date":"2026","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/42192424","citation_count":0,"is_preprint":false},{"pmid":"41905768","id":"PMC_41905768","title":"CSDE1 promotes passenger strand cleavage of miR-486.","date":"2026","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/41905768","citation_count":0,"is_preprint":false},{"pmid":"42177550","id":"PMC_42177550","title":"Loss of cold shock domain-containing protein E1 (CSDE1) function enhances mRNA stability of interleukin-6 and promotes malignant transformation in endometrial cancer cells.","date":"2026","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/42177550","citation_count":0,"is_preprint":false},{"pmid":"41757349","id":"PMC_41757349","title":"Liquid-liquid phase separation couples MKRN2-mediated ubiquitination of CSDE1 with neurodevelopmental disorders.","date":"2026","source":"Frontiers in cellular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/41757349","citation_count":0,"is_preprint":false},{"pmid":"42092680","id":"PMC_42092680","title":"Stress-inducible circSCLT1 scaffolds HNRNPA1/CSDE1 to amplify IL1B/NF-κB signaling in TNBC via mRNA stabilization, suppressor degradation, and stress granule shielding.","date":"2026","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/42092680","citation_count":0,"is_preprint":false},{"pmid":"42204155","id":"PMC_42204155","title":"The central precocious puberty-associated gene MKRN3 is a tumor suppressor regulating CSDE1 ubiquitination in ovarian cancer.","date":"2026","source":"Oncogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/42204155","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.11.684658","title":"mRNA isoform switching plays a crucial role in mural cumulus differentiation","date":"2025-11-13","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.11.684658","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.10.09.680815","title":"mRNA poly(A)-tail length is a battleground for coronavirus–host competition","date":"2025-10-10","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.09.680815","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.07.631786","title":"CSDE1 regulates miR-20a-5p/ TMBIM6 axis in melanoma","date":"2025-01-08","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.07.631786","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.09.632058","title":"Genome-wide CRISPR knockout screening with viral replicons for identification of host factors involved in viral replication","date":"2025-01-11","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.09.632058","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.03.06.641895","title":"ATXN2L primarily interacts with NUFIP2, the absence of ATXN2L results in NUFIP2 depletion, and the ATXN2-polyQ expansion triggers NUFIP2 accumulation","date":"2025-03-11","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.06.641895","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.07.631759","title":"Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome","date":"2025-01-08","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.07.631759","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":26045,"output_tokens":7136,"usd":0.092588,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":16441,"output_tokens":5155,"usd":0.10554,"stage2_stop_reason":"end_turn"},"total_usd":0.198128,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"CSDE1/UNR controls pro-metastatic targets VIM and RAC1 at the level of mRNA steady-state and translation elongation/termination in melanoma cells, as identified by iCLIP sequencing, RNA sequencing, and ribosome profiling combined with loss- and gain-of-function studies.\",\n      \"method\": \"iCLIP-seq, RNA-seq, ribosome profiling, loss- and gain-of-function experiments\",\n      \"journal\": \"Cancer cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal high-throughput methods combined with functional validation in the same study, replicated mechanistic targets across subsequent papers\",\n      \"pmids\": [\"27908735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CSDE1 post-transcriptionally regulates core components of hESC identity, neuroectoderm commitment, and neurogenesis, including binding FABP7 and VIM mRNAs to regulate their stability and translation, thereby maintaining the undifferentiated hESC state and preventing default neural fate.\",\n      \"method\": \"RNA-binding assays, loss-of-function (CSDE1 knockdown/overexpression), transcriptomic analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal functional experiments (KD and OE) with transcriptomic readout and direct RNA-binding validation, replicated VIM as a target from prior melanoma study\",\n      \"pmids\": [\"29129916\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CSDE1 loss-of-function in primary mouse cortical neurons causes neurite overgrowth, abnormal dendritic spine morphology, impaired synapse formation, and impaired synaptic transmission; HITS-CLIP showed Csde1 binds targets enriched in neuronal development and synaptic plasticity pathways including FMRP targets.\",\n      \"method\": \"shRNA knockdown in primary cortical neurons, HITS-CLIP, Drosophila knockdown and mutant experiments\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct KD with defined cellular phenotypes in both mouse neurons and Drosophila, HITS-CLIP for binding targets, multiple orthogonal methods\",\n      \"pmids\": [\"31579823\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CSDE1 promotes oncogene-induced senescence (OIS) in primary mouse keratinocytes by two independent mechanisms: enhancing mRNA stability of SASP factor transcripts and repressing YBX1 mRNA translation; CSDE1 depletion leads to senescence bypass, immortalization, and tumor formation (tumor suppressor role in this context).\",\n      \"method\": \"shRNA depletion of CSDE1, high-throughput transcriptomic and translation assays, YBX1 rescue experiments\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — unbiased high-throughput analyses with two mechanistically distinct pathways confirmed by rescue experiments, multiple orthogonal methods in one study\",\n      \"pmids\": [\"35021076\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CSDE1 interacts with AGO2 (the essential component of miRISC) in a manner facilitated by target mRNAs and dependent on the first cold shock domain of CSDE1; CSDE1 counteracts AGO2 binding at the 3'UTR of PMEPA1, attenuating miR-129-5p/AGO2-mediated silencing and elevating PMEPA1 expression in melanoma.\",\n      \"method\": \"Co-immunoprecipitation, RNA immunoprecipitation, functional reporter assays, domain mutagenesis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, domain mutagenesis identifying CSD1, RNA-binding functional assays in single lab with multiple orthogonal methods\",\n      \"pmids\": [\"33833398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CSDE1 promotes STAT1 dephosphorylation by stabilizing T cell protein tyrosine phosphatase (TCPTP), thereby reducing immunogenicity of tumor cells; SMYD3 mediates H3K4 trimethylation of the CSDE1 locus under mechanotransduction control, regulating CSDE1 expression.\",\n      \"method\": \"Protein interaction assays, phosphorylation assays, ChIP for H3K4me3 at CSDE1 locus, single tumor-repopulating cell tumor formation in mice\",\n      \"journal\": \"Science translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple assays (Co-IP for CSDE1-TCPTP, ChIP for SMYD3-CSDE1 locus) in single lab; abstract lacks full mechanistic detail\",\n      \"pmids\": [\"36724242\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TRIM28 acts as an E3 ligase for CSDE1 in HCC, promoting its degradation via the ubiquitin-proteasome pathway; lncRNA ARHGAP5-AS1 attenuates CSDE1-TRIM28 interaction, preventing CSDE1 degradation and allowing elevated CSDE1 to promote VIM and RAC1 translation and activate the ERK pathway.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, RNA pulldown, functional cancer cell assays\",\n      \"journal\": \"Clinical and translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP identifying TRIM28 as E3 ligase and ARHGAP5-AS1 as competitor, multiple biochemical assays in single lab\",\n      \"pmids\": [\"36354136\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A point-mutated CSDE1P5S form inhibits VSV replication by disrupting viral transcription; wild-type CSDE1 is a major cellular co-factor for VSV replication, and CSDE1P5S generates a neo-epitope recognized by non-tolerized T cells.\",\n      \"method\": \"Mutant CSDE1 expression in tumor cells, viral replication assays, compensatory viral mutation analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — specific point mutation with defined functional consequence on viral replication, single lab with multiple experimental validations\",\n      \"pmids\": [\"33772027\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CSDE1 binds transcripts involved in ribogenesis, mRNA translation, protein degradation, mitochondrial respiratory chain, and mitosis in erythroid cells; CRISPR/Cas9-mediated deletion of the first cold shock domain reduces CSDE1 function and affects RNA and protein expression of bound transcripts, including enhanced PABPC1 protein despite reduced PABPC1 mRNA (indicating post-transcriptional regulation).\",\n      \"method\": \"RNA immunoprecipitation-sequencing, CRISPR/Cas9 deletion of CSD1, RNA and protein expression analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP-seq for binding targets plus CRISPR domain deletion with functional readout, single lab\",\n      \"pmids\": [\"29422612\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CSDE1 directly interacts with BC200 lncRNA; STRAP binds BC200 indirectly via heterodimerization with CSDE1; knockdown of CSDE1 and BC200 reveal a reciprocal regulatory relationship; BC200 knockdown causes dramatic reorganization of CSDE1 into distinct nuclear foci.\",\n      \"method\": \"Proteomic analysis of BC200 RNP, reciprocal Co-IP, RNA truncation mapping, immunofluorescence after BC200 knockdown\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct interaction confirmed by reciprocal Co-IP and RNA truncation mapping, localization change validated by immunofluorescence, single lab\",\n      \"pmids\": [\"30247708\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"STRAP (Serine/Threonine kinase receptor-associated protein) is the protein most strongly associated with CSDE1 in erythroblasts; reduced STRAP expression alters mRNA and/or protein expression of several CSDE1-bound transcripts including Vim, Elavl1, Hmbs, eIF4g3, and Pabpc4, affecting ribosome function and cell cycle control.\",\n      \"method\": \"Co-immunoprecipitation, shRNA knockdown of STRAP, RNA-binding and expression analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP identifying STRAP as primary CSDE1 partner in erythroblasts, functional KD with specific transcript readouts, single lab\",\n      \"pmids\": [\"30138317\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"shRNA-mediated inhibition of Csde1 expression in mice causes failure of precerebellar neurons to complete their migration into prospective target regions, with neurons remaining in migratory paths and failing to invade the depth of the hindbrain via radial migration.\",\n      \"method\": \"shRNA knockdown in mouse, in vivo neuronal migration analysis\",\n      \"journal\": \"Neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo shRNA with specific neuronal migration phenotype, single lab\",\n      \"pmids\": [\"24012837\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CSDE1 binds ctnnb1 mRNAs (encoding β-catenin) and regulates their translation but not stability, thereby enhancing β-catenin protein levels and Wnt/β-catenin signaling activity to promote hematopoietic stem and progenitor cell generation during zebrafish development.\",\n      \"method\": \"Genetic mutants and morphants in zebrafish, RNA immunoprecipitation, protein and mRNA expression analysis\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function in zebrafish with RIP to validate direct ctnnb1 binding and translation vs. stability analysis, single lab\",\n      \"pmids\": [\"37874038\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CSDE1 promotes miR-451 biogenesis in erythroid cells by binding pre-miR-451, regulating AGO2 processing through its N-terminal domains, and interacting with PARN to promote trimming of intermediate miR-451 to mature length.\",\n      \"method\": \"RNA immunoprecipitation, in vitro cleavage assays, domain deletion/mutagenesis analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding and in vitro processing assays with domain mapping, single lab\",\n      \"pmids\": [\"37493604\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CSDE1, phosphorylated C-terminal domain (p-CTD) of RNA polymerase II, and CDK7 form a complex in TNBC cells; CSDE1 downregulation weakens RNAPII p-CTD–CDK7 interaction, reducing RNAPII p-CTD expression and decreasing RAC1 transcription.\",\n      \"method\": \"Co-immunoprecipitation identifying CSDE1/RNAPII p-CTD/CDK7 complex, CSDE1 inhibition experiments with downstream signaling readouts\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP for ternary complex, functional knockdown with mechanistic pathway readout, single lab\",\n      \"pmids\": [\"35490208\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CSDE1 directly interacts with HIV-1 Gag and NCp7; interaction with Gag is RNA-dependent and mediated by the NC domain of Gag; CSDE1 acts as an IRES trans-acting factor (ITAF), increasing HIV-1 IRES-dependent translation; NCp7 counteracts CSDE1's stimulatory effect while Gag increases it.\",\n      \"method\": \"Co-immunoprecipitation, FRET-FLIM, dual luciferase IRES assay, CSDE1 knockdown in HeLa cells, IRES point mutations\",\n      \"journal\": \"Viruses\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and FRET-FLIM for interaction, functional IRES assay with IRES point mutations supporting mechanistic model, single lab\",\n      \"pmids\": [\"36016420\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The Csde1-Strap complex binds Bach2 mRNA to couple its mRNA decay with translation, restraining the magnitude and duration of Bach2 protein expression during B cell to plasma cell differentiation; absence of Csde1 or Strap decouples Bach2 translation from mRNA decay, causing elevated and prolonged Bach2 expression and impaired plasma cell differentiation.\",\n      \"method\": \"RNA interactome capture-coupled CRISPR/Cas9 screen, Co-IP for Csde1-Strap complex, RNA immunoprecipitation for Bach2 mRNA binding, mRNA decay and translation assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR functional screen, direct complex identification, RNA-binding validation, and mRNA decay/translation uncoupling assays with functional rescue, multiple orthogonal methods\",\n      \"pmids\": [\"40133358\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CSDE1 undergoes context-dependent phosphorylation during early cellular transformation in melanoma cells, which correlates with changes in subcellular localization and promotes increased interactions with ribosomes; melanoma cells show one major CSDE1 isoform with enhanced ribosome association compared to healthy melanocytes.\",\n      \"method\": \"Long-read Nanopore sequencing, 2D gel electrophoresis, transcriptome analysis, interactome analysis (ribosome co-IP), phosphorylation mapping\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (proteomics, sequencing, interactome) in single lab identifying phosphorylation-dependent ribosome interaction\",\n      \"pmids\": [\"40883018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Csde1 directly binds the 3'UTR of Cdk6 mRNA to maintain its stability, thereby regulating CDK6 levels and controlling G1-to-S phase transition; Csde1 knockout in mice during cortical development causes prolonged G1 phase in neural progenitors, impaired proliferation, abnormal cortical lamination, and embryonic lethality.\",\n      \"method\": \"Csde1 conditional knockout in mice, CLIP-seq for 3'UTR binding, dual thymidine-labelling for cell cycle analysis, transcriptomic analysis\",\n      \"journal\": \"Neuroscience bulletin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KO with specific phenotype plus CLIP-seq identifying Cdk6 3'UTR binding and mRNA stability readout, single lab\",\n      \"pmids\": [\"40555862\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CSDE1 forms RNA-dependent biomolecular condensates (liquid-liquid phase separation) that sequester immunostimulatory viral RNAs, shielding them from RIG-I-like receptor recognition; upon viral infection, TBK1 kinase phosphorylates CSDE1, leading to condensate disassembly and relief of immune suppression; CSDE1-knockout mice show increased resistance to viral infection and enhanced interferon production.\",\n      \"method\": \"CSDE1 KO macrophages and mice, LLPS assays, TBK1 phosphorylation assays, interferon measurement, small molecule condensate disruption\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO mice with viral resistance phenotype, LLPS assays, TBK1-dependent phosphorylation mechanism, multiple orthogonal methods in single study\",\n      \"pmids\": [\"42049720\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CSDE1 forms a ternary complex with eIF3a (protein) and RPA2 mRNA, promoting RPA2 expression and enhancing nucleotide excision repair (NER) and homologous recombination (HR) DNA repair pathways; systemic CSDE1 knockout in mice increases DNA damage following X-ray irradiation or bleomycin treatment; CSDE1 also inhibits the cGAS-STING pathway through RPA2.\",\n      \"method\": \"Biotin pulldown, EMSA, Co-IP for CSDE1-eIF3a-RPA2 ternary complex, CSDE1 knockout mouse model, comet assay, immunofluorescence\",\n      \"journal\": \"Drug resistance updates\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple biochemical assays (pulldown, EMSA, Co-IP) plus KO mouse model with functional readouts, single lab\",\n      \"pmids\": [\"40398074\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CSDE1 stabilizes AGO2 protein in mouse embryonic stem cells by preventing its ubiquitination; CSDE1 also stabilizes pluripotency factors NANOG, SOX2, and OCT4 through the same anti-ubiquitination mechanism; the N-terminal CSD1 domain is required for CSDE1-AGO2 interaction and AGO2 stabilization.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, domain deletion (CSD1 mutant), Western blotting for pluripotency markers\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, ubiquitination assays, and domain mutagenesis in single lab establishing post-translational stabilization mechanism\",\n      \"pmids\": [\"41624769\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"MKRN2 E3 ubiquitin ligase directly ubiquitinates CSDE1 at four lysine residues (K81, K91, K208, K727); MKRN2 and CSDE1 form co-localized condensates via liquid-liquid phase separation; disruption of either protein abolishes condensate formation; MKRN2 KO mice display autism-spectrum-like social behavior abnormalities.\",\n      \"method\": \"Mass spectrometry screening for MKRN2 substrates, ubiquitination mutagenesis at identified lysine residues, LLPS assays in HEK293/SH-SY5Y cells, Mkrn2-knockout mouse behavioral assays\",\n      \"journal\": \"Frontiers in cellular neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS-identified substrate with mutagenesis of ubiquitination sites, LLPS assays, and in vivo KO model, single lab\",\n      \"pmids\": [\"41757349\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"MKRN3 (an E3 ubiquitin ligase) ubiquitinates CSDE1 as a major substrate in ovarian cancer cells, promoting CSDE1 proteolytic degradation and suppressing cancer cell proliferation.\",\n      \"method\": \"Mass spectrometry-based proteomics screens, ubiquitination assays, in vitro and in vivo proliferation assays with MKRN3 restoration\",\n      \"journal\": \"Oncogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS identification of CSDE1 as MKRN3 substrate with functional validation in cell and animal models, single lab\",\n      \"pmids\": [\"42204155\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CSDE1 directly binds IL-6 mRNA and negatively regulates its stability, thereby restraining IL-6 expression in endometrial cancer cells; loss of CSDE1 increases IL-6 mRNA stability and promotes malignant transformation.\",\n      \"method\": \"RNA immunoprecipitation, mRNA stability assays (CSDE1 KO vs. WT), IL-6 shRNA rescue, pharmacological IL-6 inhibition rescue\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RIP for IL-6 mRNA binding and mRNA stability assays with CRISPR KO plus functional rescue experiments, single lab\",\n      \"pmids\": [\"42177550\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CSDE1 enhances LDHA mRNA stability, leading to increased glycolytic activity and lactate production in gastric cancer, which then promotes HOXD9 transcription through H3K18 lactylation.\",\n      \"method\": \"RNA immunoprecipitation for CSDE1-LDHA mRNA interaction, chromatin immunoprecipitation for H3K18 lactylation at HOXD9 promoter, glycolytic assays, in vivo xenograft experiments\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP for direct LDHA mRNA binding, ChIP for downstream epigenetic modification, functional in vitro and in vivo assays, single lab\",\n      \"pmids\": [\"41864431\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CSDE1 promotes passenger strand cleavage of miR-486 by facilitating AGO2-dependent removal of the passenger strand miR-486-3p; loss of CSDE1 increases miR-486-3p levels and decreases in vitro cleavage efficiency; the N-terminal CSD1 domain is required for CSDE1-AGO2 interaction and this function.\",\n      \"method\": \"In vitro cleavage assays, CSDE1 KO in leukemia cells, CSD1 domain deletion, miRNA sequencing\",\n      \"journal\": \"RNA biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro cleavage reconstitution plus cell-based KO with specific miRNA quantification and domain mutagenesis, single lab\",\n      \"pmids\": [\"41905768\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CSDE1 associates with TOM20 (outer mitochondrial membrane import receptor) via its N-terminal region in an RNA-independent manner in sensory neurons; CSDE1 also associates with nuclear-encoded mitochondrial mRNAs enriched for inner membrane/matrix and oxidative phosphorylation pathways; CSDE1 depletion reduces mitochondrial-fraction abundance of electron transport chain mRNAs and selected mitochondrial proteins.\",\n      \"method\": \"CSDE1 immunoprecipitation-sequencing from dorsal root ganglion tissue, Co-IP for TOM20 interaction, N-terminal deletion for RNA-independent binding, subcellular fractionation\",\n      \"journal\": \"Antioxidants (Basel, Switzerland)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP-seq in native tissue, Co-IP with domain mapping for TOM20 interaction, fractionation to show functional consequence, single lab\",\n      \"pmids\": [\"42193230\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CSDE1 and PABPC1 form a complex that caps coronavirus poly(A) tails, slowing their shortening (deadenylation) and protecting viral mRNA stability during infection.\",\n      \"method\": \"Biochemical complex identification, poly(A)-tail length profiling during coronavirus infection\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint with complex identification but limited mechanistic detail in abstract; single lab, methods not fully described in abstract\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CSDE1 is a multi-domain RNA-binding protein (containing cold shock domains, with CSD1 being critical for AGO2 and partner interactions) that post-transcriptionally regulates target mRNA stability and translation in a context-dependent manner: it coordinates RNA regulons controlling cell identity, differentiation, and oncogenesis (promoting translation of VIM, RAC1, LDHA and stability of other targets in cancer contexts while repressing YBX1 translation and stabilizing SASP mRNAs during senescence), interacts with key protein partners including AGO2/miRISC (attenuating miRNA-mediated silencing of specific targets and promoting miR-451/miR-486 biogenesis), STRAP/UNRIP (together regulating mRNA decay coupled to translation), eIF3a (forming ternary complexes on specific mRNAs like RPA2), and TOM20 (localizing to mitochondria to regulate mitochondrial mRNAs); undergoes phosphorylation (by TBK1 during viral infection, and during early melanoma transformation) that modulates its subcellular localization, ribosome interactions, and condensate dynamics; forms liquid-liquid phase separation condensates that sequester viral RNAs from innate immune sensing; and is subject to ubiquitin-proteasome degradation mediated by E3 ligases TRIM28, MKRN2, and MKRN3, with its stability protected in some contexts by lncRNA partners.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CSDE1 (UNR) is a multi-domain, cold shock domain-containing RNA-binding protein that organizes post-transcriptional RNA regulons governing cell identity, differentiation, and oncogenesis by binding defined target mRNAs and controlling their stability and translation in a context-dependent manner [#0, #1, #16]. In cancer it acts predominantly as a pro-tumorigenic effector, driving the steady-state and translational output of pro-metastatic targets including VIM and RAC1 [#0, #6], stabilizing LDHA mRNA to fuel glycolysis and downstream H3K18-lactylation-driven transcription [#25], and reducing tumor immunogenicity by stabilizing TCPTP to promote STAT1 dephosphorylation [#5]; in other settings it is tumor-suppressive, enforcing oncogene-induced senescence by stabilizing SASP transcripts and repressing YBX1 translation [#3], and restraining IL-6 mRNA stability in endometrial cancer [#24]. CSDE1 controls developmental programs across systems—maintaining the undifferentiated hESC state and biasing against default neural fate [#1], directing precerebellar and cortical neuron migration, proliferation, and synapse formation through targets including FABP7 and the Cdk6 3'UTR [#2, #11, #18], and promoting hematopoietic stem/progenitor generation by enhancing ctnnb1/β-catenin translation [#12]. Mechanistically it works through its N-terminal first cold shock domain (CSD1), which mediates interaction with AGO2 to attenuate or redirect miRISC activity: it shields specific 3'UTRs (e.g. PMEPA1) from miRNA silencing [#4], stabilizes AGO2 and pluripotency factors against ubiquitination [#21], and promotes miR-451/miR-486 biogenesis via AGO2-dependent processing and PARN trimming [#13, #26]. CSDE1 partners with STRAP/UNRIP to couple mRNA decay to translation, for example restraining Bach2 expression during plasma cell differentiation [#10, #16], forms ternary complexes with eIF3a on RPA2 mRNA to support DNA repair and dampen cGAS-STING signaling [#20], and associates with TOM20 to localize and regulate mitochondrial mRNAs [#27]. CSDE1 undergoes regulated phosphorylation that alters its localization, ribosome association, and condensate behavior—including TBK1-mediated phosphorylation that disassembles RNA-dependent phase-separated condensates which otherwise sequester viral RNA from RIG-I-like receptors [#19, #17]—and its abundance is set by E3 ligases TRIM28, MKRN2, and MKRN3 that target it for ubiquitin-proteasome degradation [#6, #22, #23].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing whether CSDE1 has an in vivo developmental role, the first loss-of-function study showed it is required for neuronal migration, framing it as a regulator of nervous system development rather than a generic RNA-binding factor.\",\n      \"evidence\": \"shRNA knockdown in mouse with in vivo precerebellar neuron migration analysis\",\n      \"pmids\": [\"24012837\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No RNA targets identified\", \"Migration defect not linked to specific bound transcripts\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"To define how CSDE1 acts molecularly in cancer, multi-omic mapping demonstrated it binds and controls pro-metastatic mRNAs VIM and RAC1 at both stability and translation, establishing CSDE1 as a sequence-specific post-transcriptional driver of metastasis.\",\n      \"evidence\": \"iCLIP-seq, RNA-seq, ribosome profiling, and gain/loss-of-function in melanoma cells\",\n      \"pmids\": [\"27908735\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Domain requirements for target selection not resolved\", \"Upstream regulators of CSDE1 activity unknown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Asking whether CSDE1 governs cell fate decisions, work in hESCs showed it maintains the undifferentiated state and prevents default neural commitment via targets including FABP7 and VIM, generalizing its regulon concept to cell-identity control.\",\n      \"evidence\": \"RNA-binding assays and reciprocal knockdown/overexpression with transcriptomics in hESCs\",\n      \"pmids\": [\"29129916\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism distinguishing stability vs. translation control per target not resolved\", \"Partner proteins not defined\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To identify the protein machinery CSDE1 works with and its target classes, erythroid studies identified STRAP/UNRIP as its dominant partner, BC200 lncRNA as a direct binder controlling its localization, and CSD1 as functionally essential, anchoring a partner-and-domain framework.\",\n      \"evidence\": \"RIP-seq, reciprocal Co-IP, RNA truncation mapping, CRISPR CSD1 deletion, and immunofluorescence in erythroblasts\",\n      \"pmids\": [\"29422612\", \"30247708\", \"30138317\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Biochemical mechanism of STRAP-CSDE1 cooperation not defined\", \"How BC200 reorganizes CSDE1 foci unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extending the neuronal role mechanistically, HITS-CLIP and knockdown showed CSDE1 binds neuronal development/synaptic plasticity transcripts and controls neurite, spine, and synapse formation, linking its RNA targets to specific neuronal phenotypes.\",\n      \"evidence\": \"shRNA knockdown in primary cortical neurons, HITS-CLIP, and Drosophila genetics\",\n      \"pmids\": [\"31579823\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Individual causative target mRNAs for each phenotype not isolated\", \"Relationship to FMRP target overlap not mechanistically resolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Resolving how CSDE1 intersects with miRNA silencing, it was shown to bind AGO2 via CSD1 in a target-mRNA-facilitated manner and counteract miRISC at specific 3'UTRs, defining a mechanism by which it derepresses chosen targets like PMEPA1.\",\n      \"evidence\": \"Reciprocal Co-IP, RIP, domain mutagenesis, and reporter assays in melanoma\",\n      \"pmids\": [\"33833398\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generality of AGO2 antagonism across targets unknown\", \"Structural basis of CSD1-AGO2 contact not determined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Broadening CSDE1's reach beyond mRNA fate, studies revealed it stabilizes TCPTP to dampen tumor immunogenicity and that it is itself a host co-factor for VSV replication whose point mutant generates a T-cell neo-epitope, implicating it in immune evasion and viral biology.\",\n      \"evidence\": \"Protein interaction/phosphorylation assays, ChIP, single-cell tumor formation, and mutant CSDE1 viral replication assays\",\n      \"pmids\": [\"36724242\", \"33772027\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of TCPTP stabilization not detailed\", \"How wild-type CSDE1 supports VSV transcription unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Determining how CSDE1 abundance is set and how it can be oncogenic, work identified TRIM28 as an E3 ligase degrading CSDE1 (antagonized by lncRNA ARHGAP5-AS1) and placed CSDE1 in an RNAPII p-CTD/CDK7 complex driving RAC1 transcription, while a separate study showed it enforces senescence as a tumor suppressor.\",\n      \"evidence\": \"Co-IP, ubiquitination and RNA pulldown assays in HCC, ternary complex Co-IP in TNBC, and shRNA depletion with rescue in keratinocytes\",\n      \"pmids\": [\"36354136\", \"35490208\", \"35021076\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"What dictates pro-tumor vs. tumor-suppressor outcome is unresolved\", \"Stoichiometry of the RNAPII p-CTD/CDK7 complex unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Refining CSDE1's role in miRNA biogenesis and developmental signaling, it was shown to promote miR-451 maturation by directing AGO2 processing and PARN trimming, and to enhance β-catenin translation to support hematopoietic stem/progenitor cell generation.\",\n      \"evidence\": \"RIP, in vitro cleavage assays, domain mutagenesis in erythroid cells, and zebrafish genetics with RIP for ctnnb1\",\n      \"pmids\": [\"37493604\", \"37874038\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How CSDE1 switches between miRNA biogenesis and silencing-antagonist roles unknown\", \"Direct biochemical role in PARN recruitment not fully defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Integrating CSDE1's regulatory logic and biophysics, studies established the Csde1-Strap complex couples Bach2 mRNA decay to translation during plasma cell differentiation, defined a TBK1-phosphorylation-controlled condensate that sequesters viral RNA from RLRs, showed eIF3a/RPA2 ternary complexes support DNA repair, and demonstrated phosphorylation-dependent ribosome association during transformation.\",\n      \"evidence\": \"RNA-interactome CRISPR screen with decay/translation assays, KO mice with LLPS and TBK1 phosphorylation assays, biotin pulldown/EMSA/Co-IP with KO mouse repair assays, and Nanopore/2D-gel/interactome proteomics\",\n      \"pmids\": [\"40133358\", \"42049720\", \"40398074\", \"40883018\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Phosphosites and kinases governing each context not unified\", \"Determinants of condensate composition beyond viral RNA unclear\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Expanding CSDE1's interactome and regulation, recent work showed it stabilizes AGO2 and pluripotency factors against ubiquitination via CSD1, promotes miR-486 passenger-strand cleavage, controls Cdk6, LDHA, and IL-6 mRNAs across cancers, localizes to mitochondria via TOM20, and is degraded by E3 ligases MKRN2 (forming co-condensates) and MKRN3.\",\n      \"evidence\": \"Co-IP/ubiquitination/domain-deletion assays, in vitro cleavage with KO and miRNA-seq, CLIP-seq and RIP with stability assays, TOM20 Co-IP with fractionation, and MS-based substrate screens with LLPS and KO models\",\n      \"pmids\": [\"41624769\", \"41905768\", \"40555862\", \"41864431\", \"42177550\", \"42193230\", \"41757349\", \"42204155\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether ubiquitination sites overlap across MKRN2/MKRN3/TRIM28 unknown\", \"Functional consequence of mitochondrial mRNA regulation in disease unclear\", \"How phase separation integrates with degradation not resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved what molecular features determine whether CSDE1 stabilizes versus destabilizes a given mRNA and whether it acts as an oncogene or tumor suppressor in a particular cellular context.\",\n      \"evidence\": \"Not addressed by the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No unifying rule for stability vs. translation control\", \"No structural model of CSDE1 engaging targets with AGO2/eIF3a/STRAP\", \"Context-determining cofactors and modifications not mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 1, 4, 8, 12, 18, 24, 25, 27]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [0, 12, 15, 16, 17]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [13, 26]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 21]},\n      {\"term_id\": \"GO:0140313\", \"supporting_discovery_ids\": [19]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 17]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [27]},\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [17]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 13, 16, 26]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 6, 24, 25]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 2, 11, 12, 18]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [5, 16, 19]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [20]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [6, 21, 22, 23]}\n    ],\n    \"complexes\": [\n      \"CSDE1-STRAP complex\",\n      \"CSDE1-eIF3a-RPA2 ternary complex\",\n      \"CSDE1-RNAPII p-CTD-CDK7 complex\"\n    ],\n    \"partners\": [\n      \"AGO2\",\n      \"STRAP\",\n      \"eIF3a\",\n      \"TRIM28\",\n      \"MKRN2\",\n      \"MKRN3\",\n      \"TOM20\",\n      \"PABPC1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}