{"gene":"STAU2","run_date":"2026-06-10T07:46:42","timeline":{"discoveries":[{"year":2017,"finding":"UPF1 interacts with STAU2 and this interaction is necessary for proper assembly of stalled polysomes, transport, and local translation from STAU2 RNA granules in rat hippocampal neurons, and for mGluR-LTD synaptic plasticity.","method":"Co-immunoprecipitation, knockdown experiments in rat hippocampal neurons, mGluR-LTD assay","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction and functional knockdown with defined plasticity readout, single lab but multiple methods","pmids":["28821679"],"is_preprint":false},{"year":2021,"finding":"Chicken STAU2 interacts with EV-A71/H5N1 AIV non-structural protein NS1 and promotes viral replication by enhancing nuclear export of NS1 mRNA.","method":"Affinity purification mass spectrometry (AP-MS), co-immunoprecipitation","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — AP-MS and Co-IP with functional replication assay, single lab","pmids":["33968009"],"is_preprint":false},{"year":2019,"finding":"Stau2 downregulation in mouse cerebellar Purkinje cells leads to increased dendritic GluD2 (glutamate receptor ionotropic delta subunit 2) expression, particularly upon physical activity, establishing a role for STAU2 in regulating GluD2 levels in cerebellar synaptogenesis.","method":"Stau2 gene-trap mouse model (Stau2GT), immunofluorescence, behavioral motor coordination assays","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function mouse model with specific molecular and behavioral readouts, single lab","pmids":["30979012"],"is_preprint":false},{"year":2016,"finding":"STAU2 colocalizes with the spindle at meiotic stages MI and MII in mouse oocytes, and its colocalization requires both microtubule integrity and normal microtubule dynamics. Morpholino-mediated Stau2 knockdown disrupts spindle formation, chromosome alignment, and microtubule-kinetochore attachment, arresting oocytes at MI with activated spindle assembly checkpoint (SAC).","method":"Immunofluorescence localization, morpholino knockdown, nocodazole/taxol treatment, MAD1 kinetochore staining","journal":"Cell cycle","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with specific spindle and checkpoint readouts, single lab with multiple orthogonal methods","pmids":["27433972"],"is_preprint":false},{"year":2021,"finding":"STAU2 binds a complex and temporally regulated RNA cargo during mouse corticogenesis, including stable cargo involved in translation and chromosome organization, and dynamic cargo involved in neurogenesis and IPC versus neuronal fate determination. STAU2 preferentially distributes into intermediate progenitor cells (IPCs) during asymmetric divisions.","method":"RNA-immunoprecipitation with sequencing (RIP-seq) across four cortical developmental stages, knockdown of STAU2 target Taf13","journal":"Development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP-seq across multiple stages with functional validation of one cargo target, single lab","pmids":["34345913"],"is_preprint":false},{"year":2024,"finding":"EV-A71 3C protease interacts with STAU2 and cleaves it at the Q507-G508 site. Overexpression of STAU2 promotes EV-A71 replication, while siRNA depletion inhibits it. The cleavage product (508–570 aa) has activity that promotes EV-A71 replication.","method":"Co-immunoprecipitation, immunofluorescence assay, site-directed mutagenesis of cleavage site, overexpression and siRNA knockdown with VP1 Western blot readout, truncation mutant constructs","journal":"Virology journal","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — Co-IP, mutagenesis identifying specific cleavage site, truncation mutants, gain- and loss-of-function in same study","pmids":["39272111"],"is_preprint":false},{"year":2021,"finding":"STAU2 protein levels are regulated by caspases (which partially degrade STAU2) and the CHK1 kinase pathway (which counterbalances caspase-mediated degradation). CRISPR/Cas9 and RNAi-mediated STAU2 depletion in non-transformed hTERT-RPE1 cells facilitates cell proliferation, indicating STAU2 influences cell cycle progression. Proximity proteomics identified STAU2 interactors involved in RNA translation, localization, splicing, decay, ribosome biogenesis, and DNA damage response.","method":"CRISPR/Cas9 knockout, RNAi knockdown, caspase inhibitor treatment, CHK1 pathway inhibition, STAU2/biotinylase fusion protein proximity proteomics","journal":"BMC molecular and cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple genetic and pharmacological perturbations with defined cell cycle and proteomic readouts, single lab","pmids":["33663378"],"is_preprint":false},{"year":2023,"finding":"RNF216, a ubiquitin E3 ligase, interacts with STAU2 and promotes its degradation via the ubiquitin-proteasome pathway. In RNF216-knockout mice, STAU2 levels in the hypothalamus are increased compared to wild-type mice.","method":"Co-immunoprecipitation, RNF216 knockout mouse model, Western blot, RNA sequencing","journal":"Development, growth & differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction and in vivo knockout model with protein level readout, single lab","pmids":["37439148"],"is_preprint":false},{"year":2025,"finding":"STAU2 directly binds and regulates Palladin (PALLD) mRNA and mediates IQGAP1, promoting pancreatic cancer cell metastasis via the epithelial-mesenchymal transition (EMT) pathway. An ASO targeting STAU2 suppresses PDAC progression and metastasis in vitro and in vivo.","method":"RNA-binding assays, knockdown/overexpression, ASO treatment, in vitro and in vivo PDAC models","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA binding and functional EMT readout with in vivo ASO validation, single lab","pmids":["40539383"],"is_preprint":false},{"year":2026,"finding":"STAU2 phase separates to form dynamic condensates in dendrites of hippocampal neurons, recruiting specific mRNAs into mobile RNP granules transported along microtubules. These condensates undergo a liquid-to-gel transition that stabilizes mRNAs and represses their translation. Disrupting STAU2 condensation impairs RNP formation and anterograde mRNA delivery; overexpression promotes oversized, less mobile granules and impairs dendritic elongation. Synaptic activity bidirectionally remodels STAU2 condensates in parallel with changes in local translation.","method":"Live imaging of STAU2 condensates, phase separation assays, overexpression and condensation-disruption mutants, dendritic morphology assays, activity-dependent translation readouts","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging and functional mutants with specific morphological and translational readouts, single lab, not yet replicated","pmids":["42210778"],"is_preprint":false},{"year":2025,"finding":"Loss of STAU2 in human iPSC-derived cells disrupts neuroepithelial cell identity and accelerates neural differentiation by altering key transcription factor activity and driving early metabolic transitions, resulting in neural progenitor exhaustion and reduced organoid size. STAU2 also regulates miRNA host gene expression, affecting miRNA-mediated post-transcriptional control in progenitor cells.","method":"STAU2 knockout iPSCs, single-cell RNA sequencing (scRNA-seq), organoid morphology assessment","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint, single lab, scRNA-seq without direct mechanistic validation of pathway placement","pmids":[],"is_preprint":true}],"current_model":"STAU2 is a double-stranded RNA-binding protein that assembles target mRNAs into ribonucleoprotein (RNP) granules—which can undergo liquid-to-gel phase transitions—for anterograde transport along microtubules to dendrites, where synaptic activity remodels these condensates to permit local translation; its stability is regulated by caspase-mediated degradation and the CHK1 pathway, and by ubiquitin-proteasome-dependent degradation via the E3 ligase RNF216; it interacts with UPF1 to form stalled polysome granules required for mGluR-LTD plasticity; it is required for spindle integrity during mouse oocyte meiosis; it delivers temporally regulated RNA cargo to intermediate progenitor cells during corticogenesis; and it is cleaved by EV-A71 3C protease at Q507-G508, with the resulting fragment promoting viral replication."},"narrative":{"mechanistic_narrative":"STAU2 is a double-stranded RNA-binding protein that assembles target mRNAs into ribonucleoprotein (RNP) granules for microtubule-based transport and locally regulated translation, with prominent roles in neuronal and neurodevelopmental contexts [PMID:42210778, PMID:34345913]. In hippocampal dendrites, STAU2 phase separates into dynamic condensates that recruit specific mRNAs into mobile RNP granules transported anterogradely along microtubules; these condensates undergo a liquid-to-gel transition that stabilizes mRNAs and represses their translation, and synaptic activity bidirectionally remodels them in parallel with changes in local translation [PMID:42210778]. STAU2 interacts with UPF1 to assemble stalled polysomes whose transport and local translation are required for mGluR-LTD synaptic plasticity [PMID:28821679]. During mouse corticogenesis STAU2 binds a temporally regulated mRNA cargo and partitions asymmetrically into intermediate progenitor cells, delivering transcripts that influence neurogenic fate [PMID:34345913], and its loss in human iPSC-derived progenitors disrupts neuroepithelial identity and accelerates neural differentiation. Beyond the nervous system, STAU2 localizes to the meiotic spindle in mouse oocytes, where it is required for spindle formation, chromosome alignment, and satisfaction of the spindle assembly checkpoint [PMID:27433972], and it influences cell-cycle progression in non-transformed cells [PMID:33663378]. STAU2 protein abundance is controlled by caspase-mediated cleavage counterbalanced by the CHK1 pathway [PMID:33663378] and by ubiquitin-proteasome degradation through the E3 ligase RNF216 [PMID:37439148]. STAU2 is exploited during viral infection: it promotes EV-A71 replication and is cleaved by the EV-A71 3C protease at Q507-G508 to yield a fragment that itself enhances replication [PMID:39272111], and it supports avian influenza/EV-A71 replication via interaction with NS1 [PMID:33968009]. STAU2 also directly binds Palladin (PALLD) mRNA to promote epithelial-mesenchymal transition and metastasis in pancreatic cancer [PMID:40539383].","teleology":[{"year":2016,"claim":"Established a non-neuronal cell-division function by showing STAU2 is a spindle-associated factor whose loss arrests meiosis, broadening its role beyond mRNA transport.","evidence":"Immunofluorescence, morpholino knockdown, and microtubule perturbation in mouse oocytes with SAC readout","pmids":["27433972"],"confidence":"Medium","gaps":["Whether spindle function depends on RNA-binding or mRNA cargo delivery is unresolved","No direct spindle-localized mRNA targets identified","Single-lab loss-of-function only"]},{"year":2017,"claim":"Identified UPF1 as a functional partner that links STAU2 RNA granules to stalled-polysome assembly and a defined plasticity output, connecting transport granules to mGluR-LTD.","evidence":"Co-IP, knockdown, and mGluR-LTD assay in rat hippocampal neurons","pmids":["28821679"],"confidence":"Medium","gaps":["mRNA targets of the STAU2-UPF1 stalled-polysome state not defined","Mechanism by which translation is stalled then released is unknown"]},{"year":2019,"claim":"Provided in vivo evidence that STAU2 restrains a specific synaptic receptor, showing it tunes GluD2 levels during cerebellar synaptogenesis.","evidence":"Stau2 gene-trap mouse, immunofluorescence, and motor behavior assays","pmids":["30979012"],"confidence":"Medium","gaps":["Direct binding of STAU2 to GluD2 mRNA not shown","Whether regulation is translational or stability-based unclear"]},{"year":2021,"claim":"Resolved how STAU2 contributes to neural cell fate by mapping a temporally dynamic mRNA cargo and showing asymmetric partitioning into intermediate progenitor cells during corticogenesis.","evidence":"RIP-seq across four cortical stages with knockdown validation of the cargo Taf13","pmids":["34345913"],"confidence":"Medium","gaps":["Only one cargo functionally validated","Mechanism driving asymmetric STAU2 partitioning unknown"]},{"year":2021,"claim":"Defined post-translational control of STAU2 abundance and a cell-proliferation phenotype, showing caspase cleavage opposed by CHK1 signaling and a proximity interactome spanning RNA metabolism and DNA damage response.","evidence":"CRISPR/RNAi depletion, caspase/CHK1 inhibition, and proximity proteomics in hTERT-RPE1 cells","pmids":["33663378"],"confidence":"Medium","gaps":["Caspase cleavage sites not mapped","Functional consequences of individual proximity interactors not tested"]},{"year":2021,"claim":"Showed STAU2 is co-opted by viruses, interacting with NS1 to enhance nuclear export of NS1 mRNA and promote viral replication.","evidence":"AP-MS and Co-IP with replication assay in chicken system","pmids":["33968009"],"confidence":"Medium","gaps":["Direct RNA-binding contribution to NS1 mRNA export not separated from protein interaction","Single-lab finding"]},{"year":2023,"claim":"Identified a ubiquitin-proteasome route for STAU2 turnover by showing RNF216 binds STAU2 and controls its levels in vivo.","evidence":"Co-IP, RNF216 knockout mouse, Western blot, and RNA-seq","pmids":["37439148"],"confidence":"Medium","gaps":["Ubiquitination sites on STAU2 not mapped","Physiological consequences of STAU2 accumulation in hypothalamus not defined"]},{"year":2024,"claim":"Pinpointed a precise viral proteolytic event, mapping EV-A71 3C protease cleavage of STAU2 at Q507-G508 and showing the resulting fragment itself promotes viral replication.","evidence":"Co-IP, cleavage-site mutagenesis, truncation mutants, and gain/loss-of-function with VP1 readout","pmids":["39272111"],"confidence":"High","gaps":["Molecular activity of the 508-570 fragment that drives replication is unknown","Whether endogenous cleavage occurs at physiological infection levels not established"]},{"year":2025,"claim":"Extended STAU2 function to cancer, showing direct binding to PALLD mRNA drives EMT and metastasis and that an antisense oligonucleotide suppresses pancreatic cancer progression.","evidence":"RNA-binding assays, knockdown/overexpression, and ASO treatment in PDAC models in vitro and in vivo","pmids":["40539383"],"confidence":"Medium","gaps":["How STAU2 regulates PALLD mRNA mechanistically (stability vs translation) not fully resolved","Relationship between IQGAP1 mediation and PALLD binding unclear"]},{"year":2025,"claim":"Implicated STAU2 in maintaining human neuroepithelial identity, showing its loss accelerates differentiation and exhausts progenitors with disrupted miRNA host-gene regulation.","evidence":"STAU2 knockout iPSCs, scRNA-seq, and organoid morphology (preprint)","pmids":[],"confidence":"Low","gaps":["Preprint, not peer reviewed","scRNA-seq without direct mechanistic validation of pathway placement","Direct mRNA targets driving the phenotype not defined"]},{"year":2026,"claim":"Provided a biophysical mechanism for STAU2 granules, showing phase separation into dendritic condensates that undergo liquid-to-gel transition to stabilize and repress mRNAs and enable activity-dependent local translation.","evidence":"Live imaging, phase-separation assays, condensation-disruption and overexpression mutants in hippocampal neurons","pmids":["42210778"],"confidence":"Medium","gaps":["Sequence determinants of STAU2 condensation not mapped","Molecular trigger of the activity-dependent gel-to-liquid remodeling unknown","Not yet independently replicated"]},{"year":null,"claim":"How STAU2's RNA-binding activity is mechanistically coupled to its distinct cellular outputs—spindle integrity, condensate dynamics, viral hijacking, and cancer metastasis—remains unresolved.","evidence":"No single study integrates the RNA-binding, phase-separation, and protein-interaction functions across these contexts","pmids":[],"confidence":"Low","gaps":["No structural model linking RNA binding to condensation","Whether spindle and viral roles require mRNA cargo is unknown","Unifying cargo recognition code not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[4,8,9]},{"term_id":"GO:0140313","term_label":"molecular sequestering activity","supporting_discovery_ids":[9]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[3,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[9]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,4,9]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[0,2,9]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[4,10]}],"complexes":[],"partners":["UPF1","RNF216","NS1","EV-A71 3C PROTEASE","IQGAP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NUL3","full_name":"Double-stranded RNA-binding protein Staufen homolog 2","aliases":[],"length_aa":570,"mass_kda":62.6,"function":"RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite. As protein synthesis occurs within the dendrite, the localization of specific mRNAs to dendrites may be a prerequisite for neurite outgrowth and plasticity at sites distant from the cell body (By similarity)","subcellular_location":"Cytoplasm; Nucleus; Nucleus, nucleolus; Endoplasmic reticulum","url":"https://www.uniprot.org/uniprotkb/Q9NUL3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/STAU2","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DDOST","stoichiometry":0.2},{"gene":"DDX21","stoichiometry":0.2},{"gene":"DHX9","stoichiometry":0.2},{"gene":"DRG1","stoichiometry":0.2},{"gene":"IGF2BP1","stoichiometry":0.2},{"gene":"ILF3","stoichiometry":0.2},{"gene":"OST4","stoichiometry":0.2},{"gene":"RACK1","stoichiometry":0.2},{"gene":"RBM14","stoichiometry":0.2},{"gene":"RBM8A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/STAU2","total_profiled":1310},"omim":[{"mim_id":"605920","title":"STAUFEN DOUBLE-STRANDED RNA-BINDING PROTEIN 2; STAU2","url":"https://www.omim.org/entry/605920"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/STAU2"},"hgnc":{"alias_symbol":["39K2"],"prev_symbol":[]},"alphafold":{"accession":"Q9NUL3","domains":[{"cath_id":"3.30.160.20","chopping":"10-73","consensus_level":"high","plddt":94.0242,"start":10,"end":73},{"cath_id":"3.30.160.20","chopping":"97-119_142-181","consensus_level":"high","plddt":88.2792,"start":97,"end":181},{"cath_id":"3.30.160.20","chopping":"210-275","consensus_level":"high","plddt":91.2524,"start":210,"end":275},{"cath_id":"3.30.160.20","chopping":"309-374","consensus_level":"high","plddt":91.0048,"start":309,"end":374}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NUL3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NUL3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NUL3-F1-predicted_aligned_error_v6.png","plddt_mean":70.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=STAU2","jax_strain_url":"https://www.jax.org/strain/search?query=STAU2"},"sequence":{"accession":"Q9NUL3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NUL3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NUL3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NUL3"}},"corpus_meta":[{"pmid":"21148689","id":"PMC_21148689","title":"Wide host range and strong lytic activity of Staphylococcus aureus lytic phage Stau2.","date":"2010","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/21148689","citation_count":65,"is_preprint":false},{"pmid":"28821679","id":"PMC_28821679","title":"UPF1 Governs Synaptic Plasticity through Association with a STAU2 RNA Granule.","date":"2017","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/28821679","citation_count":22,"is_preprint":false},{"pmid":"33968009","id":"PMC_33968009","title":"Viral-Host Interactome Analysis Reveals Chicken STAU2 Interacts With Non-structural Protein 1 and Promotes the Replication of H5N1 Avian Influenza Virus.","date":"2021","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/33968009","citation_count":14,"is_preprint":false},{"pmid":"30979012","id":"PMC_30979012","title":"Altered Glutamate Receptor Ionotropic Delta Subunit 2 Expression in Stau2-Deficient Cerebellar Purkinje Cells in the Adult Brain.","date":"2019","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30979012","citation_count":12,"is_preprint":false},{"pmid":"35892886","id":"PMC_35892886","title":"Systematic Identification of the RNA-Binding Protein STAU2 as a Key Regulator of Pancreatic Adenocarcinoma.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/35892886","citation_count":8,"is_preprint":false},{"pmid":"27433972","id":"PMC_27433972","title":"RNA- binding protein Stau2 is important for spindle integrity and meiosis progression in mouse oocytes.","date":"2016","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/27433972","citation_count":8,"is_preprint":false},{"pmid":"33441653","id":"PMC_33441653","title":"Quantitative STAU2 measurement in lymphocytes for breast cancer risk assessment.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33441653","citation_count":8,"is_preprint":false},{"pmid":"26706853","id":"PMC_26706853","title":"Genomic analysis of Staphylococcus phage Stau2 isolated from medical specimen.","date":"2015","source":"Virus genes","url":"https://pubmed.ncbi.nlm.nih.gov/26706853","citation_count":6,"is_preprint":false},{"pmid":"34345913","id":"PMC_34345913","title":"STAU2 binds a complex RNA cargo that changes temporally with production of diverse intermediate progenitor cells during mouse corticogenesis.","date":"2021","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/34345913","citation_count":5,"is_preprint":false},{"pmid":"38082412","id":"PMC_38082412","title":"The genetics of gaits in Icelandic horses goes beyond DMRT3, with RELN and STAU2 identified as two new candidate genes.","date":"2023","source":"Genetics, selection, evolution : GSE","url":"https://pubmed.ncbi.nlm.nih.gov/38082412","citation_count":4,"is_preprint":false},{"pmid":"39272111","id":"PMC_39272111","title":"Cleavage of Stau2 by 3C protease promotes EV-A71 replication.","date":"2024","source":"Virology journal","url":"https://pubmed.ncbi.nlm.nih.gov/39272111","citation_count":2,"is_preprint":false},{"pmid":"33663378","id":"PMC_33663378","title":"STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells.","date":"2021","source":"BMC molecular and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/33663378","citation_count":2,"is_preprint":false},{"pmid":"40539383","id":"PMC_40539383","title":"ASO Therapy Targeting STAU2 to Inhibit Pancreatic Ductal Adenocarcinoma Progression and Metastasis by Regulating the PALLD-Mediated EMT Signaling Pathway.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40539383","citation_count":1,"is_preprint":false},{"pmid":"40185812","id":"PMC_40185812","title":"Genetic influence of a STAU2 frameshift mutation and RELN regulatory elements on performance in Icelandic horses.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40185812","citation_count":1,"is_preprint":false},{"pmid":"37439148","id":"PMC_37439148","title":"RNF216 affects the stability of STAU2 in the hypothalamus.","date":"2023","source":"Development, growth & differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/37439148","citation_count":0,"is_preprint":false},{"pmid":"39289190","id":"PMC_39289190","title":"Energy spectra with the Dirac equation of the q-deformed generalized Pöschl-Teller potential via the Feynman approach for  .","date":"2024","source":"Journal of molecular modeling","url":"https://pubmed.ncbi.nlm.nih.gov/39289190","citation_count":0,"is_preprint":false},{"pmid":"42210778","id":"PMC_42210778","title":"Fine-Tuned Regulation of mRNA Translation and Transport by STAU2 Condensate Facilitates Neuronal Development and Plasticity.","date":"2026","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/42210778","citation_count":0,"is_preprint":false},{"pmid":"31305598","id":"PMC_31305598","title":"Erratum: Graber et al., \"UPF1 Governs Synaptic Plasticity through Association with a STAU2 RNA Granule\".","date":"2017","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/31305598","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.02.679988","title":"Staufen2 modulates the temporal dynamics of human neurogenesis  <i>in vitro</i>","date":"2025-10-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.02.679988","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11671,"output_tokens":2763,"usd":0.038229,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10028,"output_tokens":3775,"usd":0.072258,"stage2_stop_reason":"end_turn"},"total_usd":0.110487,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"UPF1 interacts with STAU2 and this interaction is necessary for proper assembly of stalled polysomes, transport, and local translation from STAU2 RNA granules in rat hippocampal neurons, and for mGluR-LTD synaptic plasticity.\",\n      \"method\": \"Co-immunoprecipitation, knockdown experiments in rat hippocampal neurons, mGluR-LTD assay\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction and functional knockdown with defined plasticity readout, single lab but multiple methods\",\n      \"pmids\": [\"28821679\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Chicken STAU2 interacts with EV-A71/H5N1 AIV non-structural protein NS1 and promotes viral replication by enhancing nuclear export of NS1 mRNA.\",\n      \"method\": \"Affinity purification mass spectrometry (AP-MS), co-immunoprecipitation\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — AP-MS and Co-IP with functional replication assay, single lab\",\n      \"pmids\": [\"33968009\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Stau2 downregulation in mouse cerebellar Purkinje cells leads to increased dendritic GluD2 (glutamate receptor ionotropic delta subunit 2) expression, particularly upon physical activity, establishing a role for STAU2 in regulating GluD2 levels in cerebellar synaptogenesis.\",\n      \"method\": \"Stau2 gene-trap mouse model (Stau2GT), immunofluorescence, behavioral motor coordination assays\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function mouse model with specific molecular and behavioral readouts, single lab\",\n      \"pmids\": [\"30979012\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"STAU2 colocalizes with the spindle at meiotic stages MI and MII in mouse oocytes, and its colocalization requires both microtubule integrity and normal microtubule dynamics. Morpholino-mediated Stau2 knockdown disrupts spindle formation, chromosome alignment, and microtubule-kinetochore attachment, arresting oocytes at MI with activated spindle assembly checkpoint (SAC).\",\n      \"method\": \"Immunofluorescence localization, morpholino knockdown, nocodazole/taxol treatment, MAD1 kinetochore staining\",\n      \"journal\": \"Cell cycle\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with specific spindle and checkpoint readouts, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"27433972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"STAU2 binds a complex and temporally regulated RNA cargo during mouse corticogenesis, including stable cargo involved in translation and chromosome organization, and dynamic cargo involved in neurogenesis and IPC versus neuronal fate determination. STAU2 preferentially distributes into intermediate progenitor cells (IPCs) during asymmetric divisions.\",\n      \"method\": \"RNA-immunoprecipitation with sequencing (RIP-seq) across four cortical developmental stages, knockdown of STAU2 target Taf13\",\n      \"journal\": \"Development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP-seq across multiple stages with functional validation of one cargo target, single lab\",\n      \"pmids\": [\"34345913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"EV-A71 3C protease interacts with STAU2 and cleaves it at the Q507-G508 site. Overexpression of STAU2 promotes EV-A71 replication, while siRNA depletion inhibits it. The cleavage product (508–570 aa) has activity that promotes EV-A71 replication.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence assay, site-directed mutagenesis of cleavage site, overexpression and siRNA knockdown with VP1 Western blot readout, truncation mutant constructs\",\n      \"journal\": \"Virology journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — Co-IP, mutagenesis identifying specific cleavage site, truncation mutants, gain- and loss-of-function in same study\",\n      \"pmids\": [\"39272111\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"STAU2 protein levels are regulated by caspases (which partially degrade STAU2) and the CHK1 kinase pathway (which counterbalances caspase-mediated degradation). CRISPR/Cas9 and RNAi-mediated STAU2 depletion in non-transformed hTERT-RPE1 cells facilitates cell proliferation, indicating STAU2 influences cell cycle progression. Proximity proteomics identified STAU2 interactors involved in RNA translation, localization, splicing, decay, ribosome biogenesis, and DNA damage response.\",\n      \"method\": \"CRISPR/Cas9 knockout, RNAi knockdown, caspase inhibitor treatment, CHK1 pathway inhibition, STAU2/biotinylase fusion protein proximity proteomics\",\n      \"journal\": \"BMC molecular and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple genetic and pharmacological perturbations with defined cell cycle and proteomic readouts, single lab\",\n      \"pmids\": [\"33663378\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RNF216, a ubiquitin E3 ligase, interacts with STAU2 and promotes its degradation via the ubiquitin-proteasome pathway. In RNF216-knockout mice, STAU2 levels in the hypothalamus are increased compared to wild-type mice.\",\n      \"method\": \"Co-immunoprecipitation, RNF216 knockout mouse model, Western blot, RNA sequencing\",\n      \"journal\": \"Development, growth & differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction and in vivo knockout model with protein level readout, single lab\",\n      \"pmids\": [\"37439148\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"STAU2 directly binds and regulates Palladin (PALLD) mRNA and mediates IQGAP1, promoting pancreatic cancer cell metastasis via the epithelial-mesenchymal transition (EMT) pathway. An ASO targeting STAU2 suppresses PDAC progression and metastasis in vitro and in vivo.\",\n      \"method\": \"RNA-binding assays, knockdown/overexpression, ASO treatment, in vitro and in vivo PDAC models\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA binding and functional EMT readout with in vivo ASO validation, single lab\",\n      \"pmids\": [\"40539383\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"STAU2 phase separates to form dynamic condensates in dendrites of hippocampal neurons, recruiting specific mRNAs into mobile RNP granules transported along microtubules. These condensates undergo a liquid-to-gel transition that stabilizes mRNAs and represses their translation. Disrupting STAU2 condensation impairs RNP formation and anterograde mRNA delivery; overexpression promotes oversized, less mobile granules and impairs dendritic elongation. Synaptic activity bidirectionally remodels STAU2 condensates in parallel with changes in local translation.\",\n      \"method\": \"Live imaging of STAU2 condensates, phase separation assays, overexpression and condensation-disruption mutants, dendritic morphology assays, activity-dependent translation readouts\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging and functional mutants with specific morphological and translational readouts, single lab, not yet replicated\",\n      \"pmids\": [\"42210778\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of STAU2 in human iPSC-derived cells disrupts neuroepithelial cell identity and accelerates neural differentiation by altering key transcription factor activity and driving early metabolic transitions, resulting in neural progenitor exhaustion and reduced organoid size. STAU2 also regulates miRNA host gene expression, affecting miRNA-mediated post-transcriptional control in progenitor cells.\",\n      \"method\": \"STAU2 knockout iPSCs, single-cell RNA sequencing (scRNA-seq), organoid morphology assessment\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint, single lab, scRNA-seq without direct mechanistic validation of pathway placement\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"STAU2 is a double-stranded RNA-binding protein that assembles target mRNAs into ribonucleoprotein (RNP) granules—which can undergo liquid-to-gel phase transitions—for anterograde transport along microtubules to dendrites, where synaptic activity remodels these condensates to permit local translation; its stability is regulated by caspase-mediated degradation and the CHK1 pathway, and by ubiquitin-proteasome-dependent degradation via the E3 ligase RNF216; it interacts with UPF1 to form stalled polysome granules required for mGluR-LTD plasticity; it is required for spindle integrity during mouse oocyte meiosis; it delivers temporally regulated RNA cargo to intermediate progenitor cells during corticogenesis; and it is cleaved by EV-A71 3C protease at Q507-G508, with the resulting fragment promoting viral replication.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"STAU2 is a double-stranded RNA-binding protein that assembles target mRNAs into ribonucleoprotein (RNP) granules for microtubule-based transport and locally regulated translation, with prominent roles in neuronal and neurodevelopmental contexts [#9, #4]. In hippocampal dendrites, STAU2 phase separates into dynamic condensates that recruit specific mRNAs into mobile RNP granules transported anterogradely along microtubules; these condensates undergo a liquid-to-gel transition that stabilizes mRNAs and represses their translation, and synaptic activity bidirectionally remodels them in parallel with changes in local translation [#9]. STAU2 interacts with UPF1 to assemble stalled polysomes whose transport and local translation are required for mGluR-LTD synaptic plasticity [#0]. During mouse corticogenesis STAU2 binds a temporally regulated mRNA cargo and partitions asymmetrically into intermediate progenitor cells, delivering transcripts that influence neurogenic fate [#4], and its loss in human iPSC-derived progenitors disrupts neuroepithelial identity and accelerates neural differentiation [#10]. Beyond the nervous system, STAU2 localizes to the meiotic spindle in mouse oocytes, where it is required for spindle formation, chromosome alignment, and satisfaction of the spindle assembly checkpoint [#3], and it influences cell-cycle progression in non-transformed cells [#6]. STAU2 protein abundance is controlled by caspase-mediated cleavage counterbalanced by the CHK1 pathway [#6] and by ubiquitin-proteasome degradation through the E3 ligase RNF216 [#7]. STAU2 is exploited during viral infection: it promotes EV-A71 replication and is cleaved by the EV-A71 3C protease at Q507-G508 to yield a fragment that itself enhances replication [#5], and it supports avian influenza/EV-A71 replication via interaction with NS1 [#1]. STAU2 also directly binds Palladin (PALLD) mRNA to promote epithelial-mesenchymal transition and metastasis in pancreatic cancer [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Established a non-neuronal cell-division function by showing STAU2 is a spindle-associated factor whose loss arrests meiosis, broadening its role beyond mRNA transport.\",\n      \"evidence\": \"Immunofluorescence, morpholino knockdown, and microtubule perturbation in mouse oocytes with SAC readout\",\n      \"pmids\": [\"27433972\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether spindle function depends on RNA-binding or mRNA cargo delivery is unresolved\", \"No direct spindle-localized mRNA targets identified\", \"Single-lab loss-of-function only\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identified UPF1 as a functional partner that links STAU2 RNA granules to stalled-polysome assembly and a defined plasticity output, connecting transport granules to mGluR-LTD.\",\n      \"evidence\": \"Co-IP, knockdown, and mGluR-LTD assay in rat hippocampal neurons\",\n      \"pmids\": [\"28821679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"mRNA targets of the STAU2-UPF1 stalled-polysome state not defined\", \"Mechanism by which translation is stalled then released is unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Provided in vivo evidence that STAU2 restrains a specific synaptic receptor, showing it tunes GluD2 levels during cerebellar synaptogenesis.\",\n      \"evidence\": \"Stau2 gene-trap mouse, immunofluorescence, and motor behavior assays\",\n      \"pmids\": [\"30979012\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding of STAU2 to GluD2 mRNA not shown\", \"Whether regulation is translational or stability-based unclear\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Resolved how STAU2 contributes to neural cell fate by mapping a temporally dynamic mRNA cargo and showing asymmetric partitioning into intermediate progenitor cells during corticogenesis.\",\n      \"evidence\": \"RIP-seq across four cortical stages with knockdown validation of the cargo Taf13\",\n      \"pmids\": [\"34345913\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Only one cargo functionally validated\", \"Mechanism driving asymmetric STAU2 partitioning unknown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined post-translational control of STAU2 abundance and a cell-proliferation phenotype, showing caspase cleavage opposed by CHK1 signaling and a proximity interactome spanning RNA metabolism and DNA damage response.\",\n      \"evidence\": \"CRISPR/RNAi depletion, caspase/CHK1 inhibition, and proximity proteomics in hTERT-RPE1 cells\",\n      \"pmids\": [\"33663378\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Caspase cleavage sites not mapped\", \"Functional consequences of individual proximity interactors not tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Showed STAU2 is co-opted by viruses, interacting with NS1 to enhance nuclear export of NS1 mRNA and promote viral replication.\",\n      \"evidence\": \"AP-MS and Co-IP with replication assay in chicken system\",\n      \"pmids\": [\"33968009\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct RNA-binding contribution to NS1 mRNA export not separated from protein interaction\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified a ubiquitin-proteasome route for STAU2 turnover by showing RNF216 binds STAU2 and controls its levels in vivo.\",\n      \"evidence\": \"Co-IP, RNF216 knockout mouse, Western blot, and RNA-seq\",\n      \"pmids\": [\"37439148\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ubiquitination sites on STAU2 not mapped\", \"Physiological consequences of STAU2 accumulation in hypothalamus not defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Pinpointed a precise viral proteolytic event, mapping EV-A71 3C protease cleavage of STAU2 at Q507-G508 and showing the resulting fragment itself promotes viral replication.\",\n      \"evidence\": \"Co-IP, cleavage-site mutagenesis, truncation mutants, and gain/loss-of-function with VP1 readout\",\n      \"pmids\": [\"39272111\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular activity of the 508-570 fragment that drives replication is unknown\", \"Whether endogenous cleavage occurs at physiological infection levels not established\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended STAU2 function to cancer, showing direct binding to PALLD mRNA drives EMT and metastasis and that an antisense oligonucleotide suppresses pancreatic cancer progression.\",\n      \"evidence\": \"RNA-binding assays, knockdown/overexpression, and ASO treatment in PDAC models in vitro and in vivo\",\n      \"pmids\": [\"40539383\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How STAU2 regulates PALLD mRNA mechanistically (stability vs translation) not fully resolved\", \"Relationship between IQGAP1 mediation and PALLD binding unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Implicated STAU2 in maintaining human neuroepithelial identity, showing its loss accelerates differentiation and exhausts progenitors with disrupted miRNA host-gene regulation.\",\n      \"evidence\": \"STAU2 knockout iPSCs, scRNA-seq, and organoid morphology (preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Preprint, not peer reviewed\", \"scRNA-seq without direct mechanistic validation of pathway placement\", \"Direct mRNA targets driving the phenotype not defined\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Provided a biophysical mechanism for STAU2 granules, showing phase separation into dendritic condensates that undergo liquid-to-gel transition to stabilize and repress mRNAs and enable activity-dependent local translation.\",\n      \"evidence\": \"Live imaging, phase-separation assays, condensation-disruption and overexpression mutants in hippocampal neurons\",\n      \"pmids\": [\"42210778\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Sequence determinants of STAU2 condensation not mapped\", \"Molecular trigger of the activity-dependent gel-to-liquid remodeling unknown\", \"Not yet independently replicated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How STAU2's RNA-binding activity is mechanistically coupled to its distinct cellular outputs—spindle integrity, condensate dynamics, viral hijacking, and cancer metastasis—remains unresolved.\",\n      \"evidence\": \"No single study integrates the RNA-binding, phase-separation, and protein-interaction functions across these contexts\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model linking RNA binding to condensation\", \"Whether spindle and viral roles require mRNA cargo is unknown\", \"Unifying cargo recognition code not defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [4, 8, 9]},\n      {\"term_id\": \"GO:0140313\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [3, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 4, 9]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [0, 2, 9]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [4, 10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"UPF1\", \"RNF216\", \"NS1\", \"EV-A71 3C protease\", \"IQGAP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}