Affinage

STAU2

Double-stranded RNA-binding protein Staufen homolog 2 · UniProt Q9NUL3

Round 2 corrected
Length
570 aa
Mass
62.6 kDa
Annotated
2026-04-28
47 papers in source corpus 10 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STAU2 is a double-stranded RNA-binding protein that governs mRNA transport, translational control, and cell fate decisions in neuronal and progenitor cells. In hippocampal neurons, STAU2 partners with UPF1 to assemble RNA granules required for dendritic mRNA transport, stalled polysome formation, and mGluR-dependent long-term depression (PMID:28821679); during corticogenesis, it binds a temporally regulated RNA cargo and is asymmetrically partitioned into intermediate progenitor cells, coupling mRNA localization to neural lineage diversification (PMID:34345913). STAU2 protein stability is regulated by caspase-mediated cleavage counterbalanced by the CHK1 kinase pathway and by RNF216-dependent ubiquitin–proteasome degradation, and its depletion accelerates cell proliferation, linking STAU2 to cell-cycle control (PMID:33663378, PMID:37439148). Beyond the nervous system, STAU2 directly binds PALLD mRNA and mediates IQGAP1 signaling to promote epithelial-to-mesenchymal transition and metastasis in pancreatic ductal adenocarcinoma (PMID:40539383).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2016 Medium

    Establishing that STAU2 localizes to the meiotic spindle and is required for spindle integrity resolved whether STAU2 has cytoskeletal functions beyond mRNA transport, demonstrating a role in microtubule-kinetochore attachment and spindle assembly checkpoint activation in oocytes.

    Evidence Morpholino knockdown with immunofluorescence and drug perturbation of microtubule dynamics in mouse oocytes

    PMID:27433972

    Open questions at the time
    • Mechanism by which an RNA-binding protein stabilizes spindle microtubules is unknown
    • Whether STAU2 acts through local mRNA translation at the spindle or via direct protein-protein interactions is unresolved
    • Not tested in mitotic cells
  2. 2017 Medium

    Identification of UPF1 as a functional STAU2 partner established that RNA granule assembly requires UPF1 for dendritic mRNA transport and local translation, and linked this complex to mGluR-LTD, answering how STAU2 granules contribute to synaptic plasticity.

    Evidence Reciprocal co-immunoprecipitation, knockdown, live imaging, and mGluR-LTD electrophysiology in rat hippocampal neurons

    PMID:28821679

    Open questions at the time
    • Specific RNA targets within the granule that mediate LTD are not identified
    • Whether UPF1's role is catalytic (NMD-related) or structural within the granule is unclear
  3. 2019 Medium

    Demonstrating that STAU2 deficiency upregulates GluD2 and alters motor coordination in vivo extended STAU2's role from hippocampal to cerebellar circuits, establishing it as a regulator of Purkinje cell synaptogenesis and motor learning.

    Evidence Stau2 gene-trap mouse with immunofluorescence and rotarod/running-wheel behavioral assays

    PMID:30979012

    Open questions at the time
    • Whether STAU2 directly binds GluD2 mRNA or acts indirectly is not determined
    • Mechanism linking physical activity to STAU2-dependent GluD2 regulation is unknown
  4. 2021 Medium

    RIP-seq across cortical development stages and asymmetric division analyses revealed that STAU2 binds a stage-specific RNA cargo and preferentially segregates into intermediate progenitor cells, answering how post-transcriptional regulation contributes to neural progenitor diversification.

    Evidence RIP-seq at four developmental stages in mouse cortex with in vitro knockdown of target Taf13

    PMID:34345913

    Open questions at the time
    • Only one cargo (Taf13) functionally validated
    • How STAU2 is asymmetrically localized during division is mechanistically unresolved
  5. 2021 Medium

    Discovery that STAU2 protein levels are governed by opposing caspase-mediated degradation and CHK1-dependent stabilization, and that STAU2 loss accelerates proliferation, revealed a cell-cycle checkpoint role independent of its neuronal functions.

    Evidence CRISPR/Cas9 KO and RNAi in hTERT-RPE1 cells, caspase/CHK1 inhibitors, BioID proximity proteomics, proliferation assays

    PMID:33663378

    Open questions at the time
    • Whether CHK1 directly phosphorylates STAU2 or acts indirectly is unknown
    • Specific caspase(s) responsible for STAU2 cleavage not identified
    • Whether this proliferation phenotype is RNA-binding-dependent remains untested
  6. 2023 Medium

    Identification of RNF216 as a ubiquitin E3 ligase that targets STAU2 for proteasomal degradation provided a second post-translational control axis, with in vivo validation showing elevated STAU2 in RNF216 knockout hypothalamus.

    Evidence Co-immunoprecipitation and Western blot in RNF216 knockout mice

    PMID:37439148

    Open questions at the time
    • Ubiquitination sites on STAU2 not mapped
    • Functional consequence of elevated STAU2 in hypothalamus not characterized
    • Relationship between RNF216 and caspase/CHK1 regulatory axes is unexplored
  7. 2024 Medium

    Demonstration that EV-A71 protease 3C cleaves STAU2 at Q507-G508 and that the C-terminal fragment promotes viral replication revealed how a virus co-opts STAU2's RNA-binding activity, complementing earlier evidence that STAU2 promotes H5N1 replication via NS1 mRNA export.

    Evidence Co-IP, site-directed mutagenesis of cleavage site, siRNA knockdown, and overexpression of truncation constructs in EV-A71-infected cells

    PMID:39272111

    Open questions at the time
    • How the 63-amino-acid C-terminal fragment promotes replication is mechanistically unclear
    • Whether cleavage-resistant STAU2 alters viral fitness in vivo is untested
  8. 2025 Medium

    Direct binding of STAU2 to PALLD mRNA and in vivo ASO-mediated suppression of PDAC metastasis established STAU2 as a driver of epithelial-to-mesenchymal transition via PALLD/IQGAP1 signaling, extending its functional repertoire to cancer.

    Evidence RNA-binding assays, ASO treatment, in vitro and in vivo PDAC tumor models

    PMID:40539383

    Open questions at the time
    • Whether STAU2 stabilizes or translationally activates PALLD mRNA is not distinguished
    • Generalizability beyond PDAC is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of STAU2's RNA cargo selectivity, the identity of direct phosphorylation sites mediating CHK1-dependent stabilization, and whether STAU2's meiotic spindle role requires RNA binding or protein-protein interactions remain unresolved.
  • No high-resolution structure of STAU2 bound to a specific endogenous RNA target
  • CHK1 phosphorylation sites on STAU2 not mapped
  • Mechanistic link between RNA binding and spindle function is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-112316 Neuronal System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-1266738 Developmental Biology 1
Partners
IQGAP1NS1PALLDRNF216UPF1
Complex memberships
STAU2–UPF1 RNA granule

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 UPF1 interacts with the RNA-binding protein STAU2 and this interaction is necessary for proper transport and local translation from a prototypical RNA granule substrate (prototypical STAU2 RNA granule), as well as for mGluR-LTD in hippocampal neurons. UPF1 is critical for assembly of stalled polysomes in rat hippocampal neurons, and its interaction with STAU2 is required for this process. Co-immunoprecipitation, knockdown experiments, live imaging, synaptic plasticity assays (mGluR-LTD) in rat hippocampal neurons The Journal of neuroscience Medium 28821679
2021 Chicken STAU2 (Staufen double-stranded RNA-binding protein 2) physically interacts with H5N1 avian influenza virus non-structural protein 1 (NS1) and promotes viral replication by enhancing the nuclear export of NS1 mRNA. Affinity purification mass spectrometry (AP-MS), co-immunoprecipitation, knockdown/overexpression with viral replication readout Frontiers in immunology Medium 33968009
2019 Stau2 downregulation in mouse cerebellar Purkinje cells leads to increased GluD2 (glutamate receptor ionotropic delta subunit 2) expression during physical activity, and Stau2-deficient mice show altered motor coordination and enhanced motor learning, indicating Stau2 regulates GluD2 expression and Purkinje cell synaptogenesis. Stau2 gene-trap mouse model (Stau2GT), immunofluorescence, behavioral assays (rotarod, voluntary running wheel) International journal of molecular sciences Medium 30979012
2016 STAU2 colocalizes with the meiotic spindle in mouse oocytes at MI and MII stages, and its assembly on microtubules requires both microtubule integrity and normal microtubule dynamics. Morpholino-mediated Stau2 knockdown disrupts spindle formation, chromosome alignment, and microtubule-kinetochore attachment, arresting most oocytes at MI with activated spindle assembly checkpoint (MAD1 signal at kinetochores). Morpholino knockdown, immunofluorescence, nocodazole/taxol treatment, Western blot in mouse oocytes Cell cycle Medium 27433972
2021 STAU2 binds a complex and temporally regulated RNA cargo during mouse corticogenesis, with a 'stable' subset involved in chromosome organization, macromolecule localization, translation, and DNA repair, and a 'dynamic' subset changing with cortical stage and involved in neurogenesis and cell projection organization. During asymmetric divisions STAU2 preferentially distributes into intermediate progenitor cells (IPCs), delivering this RNA cargo. Knockdown of one STAU2 target, Taf13, reduced oligodendrogenesis in vitro. RNA-immunoprecipitation sequencing (RIP-seq) across four developmental stages, in vitro knockdown Development (Cambridge, England) Medium 34345913
2021 STAU2 protein steady-state levels are controlled by caspase-mediated degradation, and this is counterbalanced by the CHK1 kinase pathway. CRISPR/Cas9 and RNAi-mediated STAU2 depletion in non-transformed hTERT-RPE1 cells facilitates cell proliferation, indicating STAU2 influences cell cycle control pathways. Proximity proteomics (STAU2/biotinylase fusion) identified known STAU2 interactors in RNA translation, localization, splicing, and decay, plus nucleolar proteins of the ribosome biogenesis and DNA damage response pathways linked to CHK1. CRISPR/Cas9 KO, RNAi knockdown, caspase inhibitor treatment, CHK1 pathway inhibition, BioID proximity proteomics, cell proliferation assays BMC molecular and cell biology Medium 33663378
2023 RNF216, a ubiquitin E3 ligase, interacts with STAU2 and affects STAU2 stability through the ubiquitin-proteasome pathway. In RNF216 knockout mice, STAU2 levels in the hypothalamus are increased compared to wild-type mice, indicating RNF216 promotes STAU2 degradation. Co-immunoprecipitation, RNF216 knockout mice, Western blot, RNA sequencing Development, growth & differentiation Medium 37439148
2024 EV-A71 viral protease 3C interacts with STAU2 and cleaves it at the Q507-G508 site. Overexpression of STAU2 promotes EV-A71 VP1 protein expression and replication, whereas siRNA depletion of STAU2 inhibits viral replication. The cleavage product comprising aa 508–570 has activity that promotes EV-A71 replication. Co-immunoprecipitation, immunofluorescence assay, site-directed mutagenesis of cleavage site, Western blot (VP1 as replication readout), siRNA knockdown, overexpression of truncation constructs Virology journal Medium 39272111
2022 STAU2 directly binds and regulates the mRNA/protein of cytoskeletal associated protein Palladin (PALLD) and mediates IQ motif containing GTPase-activating protein 1 (IQGAP1), thereby promoting metastasis via the EMT pathway in pancreatic ductal adenocarcinoma cells. Knockdown of STAU2 led to decreased PAAD cell growth, migration, invasion and induced apoptosis. Knockdown/overexpression, multiple omics analyses, cell migration/invasion assays, apoptosis assays Cancers Low 35892886
2025 STAU2 directly binds Palladin (PALLD) and mediates IQGAP1, promoting PDAC metastasis via the EMT signaling pathway. An antisense oligonucleotide (ASO) targeting STAU2 effectively inhibited downstream targets and suppressed PDAC progression and metastasis in vitro and in vivo. RNA-binding assays, ASO treatment, in vitro and in vivo tumor models, Western blot, invasion/migration assays Advanced science Medium 40539383
2025 Loss of STAU2 in human iPSC-derived neural cells disrupts neuroepithelial cell identity and accelerates neural differentiation by altering key transcription factor activity and driving early metabolic transitions. STAU2 also regulates miRNA host gene expression and alters miRNA-mediated post-transcriptional control in progenitor cells, resulting in neural progenitor exhaustion, unstructured neural rosettes, and reduced organoid size. STAU2 knockout iPSCs, scRNA-seq, organoid culture, neural differentiation assays bioRxivpreprint Low

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2011 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity 286 21903422
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2000 Molecular insights into mRNA transport and local translation in the mammalian nervous system. Neuron 170 10707969
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2019 Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expression. Molecular cancer 154 31623628
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2013 Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. American journal of human genetics 136 24144296
2014 The central role of EED in the orchestration of polycomb group complexes. Nature communications 131 24457600
2010 RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5), competes with pICln for binding and modulates PRMT5 complex composition and substrate specificity. The Journal of biological chemistry 131 21081503
2010 Wide host range and strong lytic activity of Staphylococcus aureus lytic phage Stau2. Applied and environmental microbiology 65 21148689
2017 UPF1 Governs Synaptic Plasticity through Association with a STAU2 RNA Granule. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 28821679
2021 Viral-Host Interactome Analysis Reveals Chicken STAU2 Interacts With Non-structural Protein 1 and Promotes the Replication of H5N1 Avian Influenza Virus. Frontiers in immunology 12 33968009
2019 Altered Glutamate Receptor Ionotropic Delta Subunit 2 Expression in Stau2-Deficient Cerebellar Purkinje Cells in the Adult Brain. International journal of molecular sciences 12 30979012
2022 Systematic Identification of the RNA-Binding Protein STAU2 as a Key Regulator of Pancreatic Adenocarcinoma. Cancers 8 35892886
2021 Quantitative STAU2 measurement in lymphocytes for breast cancer risk assessment. Scientific reports 8 33441653
2016 RNA- binding protein Stau2 is important for spindle integrity and meiosis progression in mouse oocytes. Cell cycle (Georgetown, Tex.) 8 27433972
2015 Genomic analysis of Staphylococcus phage Stau2 isolated from medical specimen. Virus genes 6 26706853
2021 STAU2 binds a complex RNA cargo that changes temporally with production of diverse intermediate progenitor cells during mouse corticogenesis. Development (Cambridge, England) 5 34345913
2023 The genetics of gaits in Icelandic horses goes beyond DMRT3, with RELN and STAU2 identified as two new candidate genes. Genetics, selection, evolution : GSE 3 38082412
2024 Cleavage of Stau2 by 3C protease promotes EV-A71 replication. Virology journal 2 39272111
2021 STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells. BMC molecular and cell biology 2 33663378
2025 Genetic influence of a STAU2 frameshift mutation and RELN regulatory elements on performance in Icelandic horses. Scientific reports 1 40185812
2025 ASO Therapy Targeting STAU2 to Inhibit Pancreatic Ductal Adenocarcinoma Progression and Metastasis by Regulating the PALLD-Mediated EMT Signaling Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40539383
2024 Energy spectra with the Dirac equation of the q-deformed generalized Pöschl-Teller potential via the Feynman approach for . Journal of molecular modeling 0 39289190
2023 RNF216 affects the stability of STAU2 in the hypothalamus. Development, growth & differentiation 0 37439148
2017 Erratum: Graber et al., "UPF1 Governs Synaptic Plasticity through Association with a STAU2 RNA Granule". The Journal of neuroscience : the official journal of the Society for Neuroscience 0 31305598