Double-stranded RNA-binding protein Staufen homolog 2 (STAU2) is a brain-enriched member of the conserved Staufen family. It contains four double-stranded RNA-binding motifs (dsRBMs) and a C-terminal Staufen domain. STAU2 shuttles between nucleus and cytoplasm, binding structured mRNA elements and assembling them into ribonucleoprotein (RNP) granules that are transported along microtubules to dendrites in neurons. STAU2 is required for 3'-UTR-dependent anterograde mRNA transport bias in dendrites and for activity-dependent synaptic mRNA recruitment. It also participates in Staufen-mediated mRNA decay (SMD) together with UPF1. During cortical development, STAU2 segregates asymmetrically during neural progenitor divisions, promoting lineage progression. STAU2 isoforms differ in their subcellular associations: the 62 kDa isoform fractionates with light complexes, while the 59 and 52 kDa isoforms associate with high-density EDTA-resistant complexes and ribosomes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043005 neuron projection | IBA GO_REF:0000033 | ACCEPT | Summary: STAU2 is localized in the somatodendritic domain of neurons and in dendrites aligned on microtubule tracts. In rat neurons, STAU2 is present in RNA granules within neurites. IBA annotation well-supported by phylogenetic conservation and direct observations in rodent orthologs. Reason: Somatodendritic localization of STAU2 is well-established in multiple studies using rodent neurons. Duchaine et al. showed STAU2 in dendrites aligned on microtubules. Li et al. showed colocalization with RNA granules in neurites. Supporting Evidence: PMID:12140260 Stau2 is found in the somatodendritic compartment of neurons file:human/STAU2/STAU2-deep-research-bioreason-sft.md model: SFT |
| GO:0003725 double-stranded RNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: dsRNA binding is the core molecular function of STAU2, mediated by four dsRBM domains. Phylogenetically well-conserved from Drosophila Staufen. Redundant with IDA and TAS annotations below. Falcon deep research confirms STAU2 recognizes structured RNA, binding secondary structures in 3'-UTRs including complex long-range RNA hairpins rather than sequence-specific single-stranded motifs. Reason: The four dsRBM domains are the defining structural feature of STAU2. dsRNA binding has been demonstrated experimentally (IDA, TAS evidence also present) and is conserved across the Staufen family. Supporting Evidence: PMID:10585778 presence of three double-stranded RNA-binding domains file:human/STAU2/STAU2-deep-research-bioreason-sft.md model: SFT file:human/STAU2/STAU2-deep-research-falcon.md STAU2 binds **secondary structures in 3′ UTRs**, including **complex long-range RNA hairpins** |
| GO:0003729 mRNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: STAU2 binds mRNA through recognition of structured (double-stranded) regions in target transcripts. mRNA binding is central to its role in mRNA transport and SMD. Supported by phylogenetic inference from Drosophila staufen and zebrafish. Falcon deep research adds quantitative scope: review-level syntheses report ~1,200 STAU2-associated mRNAs by immunoprecipitation from rat brain and 356 neuronal mRNAs with 3'-UTRs bound by STAU2 in a mouse brain study. Reason: Multiple studies show STAU2 binds specific mRNAs. RIP-seq identified cargo mRNAs including Trim32. STAU2 binds SBS-containing mRNAs at 2-5x higher levels than STAU1. Supporting Evidence: PMID:22902295 We immunoprecipitated Stau2 to examine its cargo mRNAs PMID:23263869 two- to fivefold more of those SBS-containing mRNAs that were tested file:human/STAU2/STAU2-deep-research-falcon.md **356** neuronal mRNAs with **3′ UTRs bound by STAU2** |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Plasma membrane localization is inferred from Drosophila staufen. While STAU2 is found in membrane-associated fractions and near peripheral sites in neurons, the primary localization is cytoplasmic and in RNP granules. The plasma membrane annotation may reflect peripheral or cortical localization rather than integral membrane association. Reason: STAU2 has no transmembrane domain and is primarily a soluble cytoplasmic protein. Association with membrane fractions (as shown by PMID:19946888 in NK cells) is likely transient or peripheral. Not a core localization. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells |
| GO:0007281 germ cell development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Inferred from Drosophila staufen (essential for oocyte patterning) and C. elegans/ zebrafish orthologs. There is no direct human-specific evidence for STAU2 in germ cell development, but the Staufen family has conserved roles in germline RNA localization across species. Falcon deep research notes STAU2 is enriched in brain and gonads (in contrast to ubiquitous STAU1), consistent with a tissue-level relevance to germline biology. Reason: The role in germ cell development is well-established for Drosophila staufen and orthologs in worm and zebrafish. For human STAU2, this is a plausible inferred function but not the core characterized role (which centers on neuronal mRNA transport). Supporting Evidence: file:human/STAU2/STAU2-notes.md Drosophila Staufen protein is essential for mRNA localization during oogenesis file:human/STAU2/STAU2-deep-research-falcon.md STAU2 is described as **enriched in brain and gonads**, in contrast to more ubiquitous STAU1 |
| GO:0008298 intracellular mRNA localization | IBA GO_REF:0000033 | ACCEPT | Summary: mRNA localization is a core function of STAU2. The protein assembles mRNAs into RNP granules and mediates their transport to dendrites. Live-cell imaging confirmed STAU2-dependent 3'-UTR-mediated mRNA sorting to synapses. Falcon deep research adds a structural mechanism: a retained intron in the 3'-UTR of Calm3 mRNA mediates its STAU2- and activity-dependent dendritic localization, and dominant-negative STAU2 perturbs partitioning by reducing dendritic RNAs while increasing somatic levels. Reason: This is one of the best-characterized functions of STAU2. Multiple studies demonstrate its role in dendritic mRNA targeting and activity-dependent synaptic mRNA recruitment. Supporting Evidence: PMID:31320644 the Rgs4 3'-UTR causes an anterograde transport bias, which requires the Staufen2 protein PMID:12140260 Stau2 is found in the somatodendritic compartment of neurons file:human/STAU2/STAU2-deep-research-falcon.md a retained intron in the 3′ UTR of Calm3 mRNA mediates its STAU2- and activity-dependent localization to neuronal dendrites |
| GO:0010494 cytoplasmic stress granule | IBA GO_REF:0000033 | ACCEPT | Summary: STAU2 is recruited to stress granules upon translation inhibition or oxidative stress. This is supported by UniProt annotation (by similarity from rat) and by Ensembl ortholog transfer from rat Stau2. Reason: Stress granule localization is well-supported by similarity from the rat ortholog (Q68SB1) per UniProt. Stress granules harbor housekeeping mRNAs when translation is aborted, and STAU2 as an RNA-binding transport factor would naturally be recruited to these structures. Supporting Evidence: file:human/STAU2/STAU2-notes.md recruited to stress granules (SGs) upon inhibition of translation or oxidative stress |
| GO:0035418 protein localization to synapse | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAU2 mediates mRNA transport to synapses, which enables local protein synthesis. This indirectly supports protein localization to synapses. The IBA inference from Drosophila staufen is consistent with STAU2's role in synaptic mRNA delivery. Reason: STAU2 primarily localizes mRNA to synapses rather than directly localizing proteins. The term is a plausible but indirect consequence of STAU2's mRNA transport activity. Not the primary function. Supporting Evidence: PMID:31320644 the 3'-UTR mediates dynamic, sustained mRNA recruitment to synapses |
| GO:0043025 neuronal cell body | IBA GO_REF:0000033 | ACCEPT | Summary: STAU2 is present in neuronal cell bodies as well as dendrites. Duchaine et al. showed somatodendritic localization. The protein is expressed throughout the neuron with enrichment in soma and dendrites. Reason: Somatodendritic localization is well-established. STAU2 is present in cell bodies where it assembles RNP granules before transport to dendrites. Supporting Evidence: PMID:12140260 Stau2 is found in the somatodendritic compartment of neurons |
| GO:0098964 anterograde dendritic transport of messenger ribonucleoprotein complex | IBA GO_REF:0000033 | ACCEPT | Summary: This is a core function of STAU2. Live-cell imaging directly demonstrated that STAU2 is required for 3'-UTR-dependent anterograde transport bias in dendrites. Falcon deep research corroborates that STAU2-containing RNPs traffic bidirectionally along microtubules to deliver transcripts to dendrites. Reason: Bauer et al. 2019 showed by MS2 live-cell imaging that STAU2 is required for anterograde transport bias of Rgs4 mRNA in dendrites. This is the most specific and directly supported biological process annotation for STAU2. Supporting Evidence: PMID:31320644 the Rgs4 3'-UTR causes an anterograde transport bias, which requires the Staufen2 protein file:human/STAU2/STAU2-deep-research-falcon.md STAU2-containing RNPs **traffic bidirectionally along microtubules** to deliver transcripts to dendrites |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: STAU2 shuttles between nucleus and cytoplasm. A pool of STAU2 is present in neuronal nuclei where it colocalizes with nuclear pore protein p62. Nuclear export requires XPO5 (isoform 1) or XPO1 (isoforms 2 and 3). Reason: Nuclear localization is well-established. Monshausen et al. showed STAU2 in neuronal nuclei colocalizing with p62 and Tap. UniProt documents nucleocytoplasmic shuttling. Supporting Evidence: PMID:15970630 A pool of Staufen2 is present in neuronal nuclei and colocalizes to a large degree with p62 |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt documents nucleolar localization. STAU2 shuttles between the nucleolus, nucleus, and cytoplasm per UniProt. Falcon deep research notes that nucleolar accumulation is isoform-specific and that nuclear export can be exportin-5-dependent, indicating localization depends on isoform context. Reason: UniProt subcellular location annotation includes nucleolus. The protein shuttles through nuclear subcompartments including the nucleolus. Supporting Evidence: file:human/STAU2/STAU2-notes.md Shuttles between the nucleolus, nucleus and the cytoplasm file:human/STAU2/STAU2-deep-research-falcon.md **STAU2 isoforms** can show **isoform-specific nucleolar accumulation** and **exportin-5-dependent export** |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm is the primary localization of STAU2. The protein is a soluble cytoplasmic RNA-binding protein that assembles into RNP granules. Reason: Cytoplasmic localization is the predominant and best-characterized location for STAU2. All functional studies show STAU2 operating in the cytoplasm. Supporting Evidence: PMID:12140260 Stau2 is found in the somatodendritic compartment of neurons |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt documents ER association. STAU2-containing RNP granules are found associated with polysomes and the endoplasmic reticulum in myelinating processes (by similarity from rat). Reason: ER association is documented by UniProt and supported by similarity. This likely reflects association of STAU2-containing RNP granules with rough ER for localized translation, rather than a constitutive ER residence. Supporting Evidence: file:human/STAU2/STAU2-notes.md associated with microtubules, polysomes and the endoplasmic reticulum |
| GO:0032839 dendrite cytoplasm | IEA GO_REF:0000108 | ACCEPT | Summary: Logically inferred from involvement in anterograde dendritic transport. STAU2 is well-established in dendrite cytoplasm through multiple studies. Reason: This is a straightforward logical inference from the dendritic transport role. STAU2 is directly observed in dendrites in multiple studies. Supporting Evidence: PMID:12140260 In dendrites, Stau2 is aligned on individual tracts and colocalizes with microtubules |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | MARK AS OVER ANNOTATED | Summary: STAU2 interacts with EIF2AK2 (PKR, P19525) and DHX58 (LGP2, Q96C10) in the HI5 innate immunity interactome. Both are dsRNA-sensing proteins, consistent with STAU2's dsRNA-binding activity. This is a large-scale interactome study. Reason: Protein binding is uninformative per GO curation guidelines. The specific interactions (with EIF2AK2 and DHX58) are real but likely reflect shared dsRNA-binding activity rather than a core functional partnership for STAU2. More informative terms would describe the specific binding activities. Supporting Evidence: PMID:21903422 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MARK AS OVER ANNOTATED | Summary: STAU2 interacts with EIF2AK2 (PKR) in the kinase interaction network study. Consistent with the PMID:21903422 finding. Reason: Protein binding is uninformative. The EIF2AK2 interaction is confirmed but GO:0005515 does not capture the functional significance. Supporting Evidence: PMID:32707033 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases |
| GO:0005515 protein binding | IPI PMID:34159380 Nsp2 has the potential to be a drug target revealed by globa... | MARK AS OVER ANNOTATED | Summary: STAU2 identified as a SARS-CoV-2 Nsp2-interacting protein by AP-MS/SILAC, confirmed by BLI assay. This is a host-pathogen interaction rather than a normal physiological function. Reason: Protein binding is uninformative. The Nsp2 interaction is a viral hijacking event rather than reflecting STAU2's normal function. Supporting Evidence: PMID:34159380 Bio-layer interferometry (BLI) assay confirmed the bindings between Nsp2- and 4-interacting proteins, i.e. STAU2 (Staufen2) |
| GO:0005515 protein binding | IPI PMID:23125361 The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor ... | MARK AS OVER ANNOTATED | Summary: STAU2 interacts with TRIM71 (Q2Q1W2) via NHL repeats in an RNA-dependent manner. TRIM71 is a translational repressor, so this interaction may be functionally relevant for mRNA regulation. Reason: Protein binding is uninformative. The TRIM71 interaction is biologically interesting (RNA-dependent translational repression) but GO:0005515 does not capture the functional significance. Supporting Evidence: PMID:23125361 TRIM71 is associated with mRNAs and that it promotes translational repression and mRNA decay |
| GO:0010494 cytoplasmic stress granule | IEA GO_REF:0000107 | ACCEPT | Summary: Transferred from rat ortholog. Consistent with the IBA annotation and UniProt documentation of stress granule recruitment. Reason: Redundant with IBA annotation for the same term. Stress granule localization is well-supported. Supporting Evidence: file:human/STAU2/STAU2-notes.md recruited to stress granules (SGs) upon inhibition of translation or oxidative stress |
| GO:0019894 kinesin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Transferred from rat Stau2. Kinesin binding is consistent with STAU2's role in microtubule-dependent anterograde transport of mRNP granules in dendrites. Reason: Kinesin motors (KIF5 family) power anterograde transport along microtubules. STAU2 mediates microtubule-dependent mRNA transport, and kinesin binding would be the direct mechanistic link. Supported by rat ortholog data. Supporting Evidence: file:human/STAU2/STAU2-notes.md STAU2 is required for 3'-UTR-dependent anterograde mRNA transport bias in dendrites |
| GO:0030424 axon | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat ortholog. While STAU2 is primarily somatodendritic, some presence in axons is plausible for a neuronal RNA-binding protein. Reason: STAU2 is predominantly somatodendritic. Duchaine et al. specifically characterized it in the somatodendritic domain. Axonal presence may be minor or context-dependent. Supporting Evidence: PMID:12140260 Stau2 is found in the somatodendritic compartment of neurons |
| GO:0030425 dendrite | IEA GO_REF:0000107 | ACCEPT | Summary: Transferred from rat. Dendritic localization is one of the most well-characterized aspects of STAU2 biology. Reason: Dendritic localization is extensively documented. STAU2 is aligned on microtubule tracts in dendrites and is required for dendritic mRNA transport. Supporting Evidence: PMID:12140260 In dendrites, Stau2 is aligned on individual tracts and colocalizes with microtubules |
| GO:0030544 Hsp70 protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. Hsp70 binding may relate to stress granule dynamics or protein quality control. Not a core functional interaction for STAU2. Reason: Hsp70 interactions are common for RNA-binding proteins and may reflect stress granule co-residence or chaperone-assisted folding. Not a defining functional interaction for STAU2. |
| GO:0031965 nuclear membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. STAU2 interacts with nuclear pore protein p62 and shuttles through nuclear pores, so transient nuclear membrane association is expected. Reason: Nuclear membrane localization is likely transient, reflecting nucleocytoplasmic shuttling through nuclear pores. The interaction with p62 supports this. Supporting Evidence: PMID:15970630 Staufen2 interacts with the nuclear pore protein p62 |
| GO:0032956 regulation of actin cytoskeleton organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. This may relate to dendritic spine morphogenesis, where actin dynamics are critical. Could be an indirect effect via mRNA localization of actin-regulatory mRNAs. Reason: Likely an indirect effect of STAU2's mRNA transport activity rather than direct regulation of actin organization. Dendritic spine morphogenesis involves actin remodeling, and STAU2 may transport mRNAs encoding actin regulators. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred from rat. STAU2 is part of large mRNP complexes. This is a very generic term that does not add information beyond what is known. Reason: This is an uninformatively broad CC term. STAU2 is indeed part of mRNP complexes, but more specific terms (neuronal ribonucleoprotein granule, cytoplasmic stress granule) are more appropriate. |
| GO:0034599 cellular response to oxidative stress | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. STAU2 is recruited to stress granules upon oxidative stress per UniProt annotation (by similarity). This is a secondary response rather than a core function. Reason: Stress granule recruitment upon oxidative stress is documented, but this is a general stress response rather than a core evolved function of STAU2. The protein is not a sensor or effector of oxidative stress per se. |
| GO:0043022 ribosome binding | IEA GO_REF:0000107 | ACCEPT | Summary: Transferred from rat. Duchaine et al. showed that some STAU2 isoforms associate with ribosomes in EDTA-resistant complexes. The association is independent of translation. Reason: Ribosome binding is supported by fractionation data from Duchaine et al. Isoforms 59 kDa and 52 kDa associate with ribosomes in an EDTA-resistant manner, suggesting direct binding rather than mRNA-mediated tethering. Supporting Evidence: PMID:12140260 we also provide evidence for an interaction of some Stau2 isoforms with ribosomes |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | ACCEPT | Summary: Transferred from rat. Redundant with IBA annotation for the same term. Neuronal cell body localization is well-established. Reason: Consistent with the IBA annotation. STAU2 is found in neuronal soma. Supporting Evidence: PMID:12140260 Stau2 is found in the somatodendritic compartment of neurons |
| GO:0043198 dendritic shaft | IEA GO_REF:0000107 | ACCEPT | Summary: Transferred from rat. Consistent with dendritic localization. STAU2 is aligned along microtubule tracts in dendritic shafts. Reason: Dendritic shaft localization is directly supported by imaging data showing STAU2 aligned on microtubule tracts in dendrites. Supporting Evidence: PMID:12140260 In dendrites, Stau2 is aligned on individual tracts and colocalizes with microtubules |
| GO:0048592 eye morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. No direct evidence for STAU2 in eye morphogenesis in human. May reflect expression data or phenotype from rat. Reason: Eye morphogenesis is not part of STAU2's characterized core function. This may be a pleiotropic effect in development, potentially through mRNA localization in retinal neurons. |
| GO:0051019 mitogen-activated protein kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. MAPK binding could relate to activity-dependent regulation of STAU2 function or phosphorylation. STAU2 has multiple phosphorylation sites. Reason: STAU2 is heavily phosphorylated (multiple sites documented in UniProt), and MAPK binding may reflect regulatory interactions. Not a core molecular function. |
| GO:0051489 regulation of filopodium assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. May relate to dendritic morphogenesis through mRNA localization of cytoskeletal regulators. Reason: Likely an indirect effect of STAU2's mRNA transport function rather than a direct regulatory role in filopodium assembly. |
| GO:0051965 positive regulation of synapse assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. STAU2 delivers mRNAs to synapses, which could support synapse assembly through local translation of synaptic components. Reason: This is likely an indirect downstream effect of STAU2's mRNA transport to synapses. The Stau2-deficient mouse shows behavioral deficits consistent with impaired synaptic function, but direct regulation of synapse assembly is not demonstrated. Supporting Evidence: PMID:29496644 Stau2 contributes to novelty preference and explorative behavior |
| GO:0061003 positive regulation of dendritic spine morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. STAU2 delivers mRNAs to dendritic regions where local translation could support spine morphogenesis. Reason: Likely indirect. STAU2 transports mRNAs to dendritic regions, and local translation of structural/regulatory proteins could support spine morphogenesis. But STAU2 is not a direct morphogenetic regulator. |
| GO:0098794 postsynapse | IEA GO_REF:0000107 | ACCEPT | Summary: Transferred from rat. Consistent with STAU2's role in delivering mRNAs to synaptic sites and the demonstrated synaptic mRNA recruitment. Reason: Bauer et al. showed dynamic mRNA recruitment to synapses dependent on STAU2 and neuronal activity. Postsynaptic localization is consistent with the primary function. Supporting Evidence: PMID:31320644 the 3'-UTR mediates dynamic, sustained mRNA recruitment to synapses |
| GO:0098964 anterograde dendritic transport of messenger ribonucleoprotein complex | IEA GO_REF:0000107 | ACCEPT | Summary: Transferred from rat. Redundant with IBA annotation for the same term. This is a core function of STAU2. Reason: Consistent with the IBA annotation. Directly supported by live-cell imaging. Supporting Evidence: PMID:31320644 the Rgs4 3'-UTR causes an anterograde transport bias, which requires the Staufen2 protein |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. STAU2 delivers mRNAs to excitatory synapses. The behavioral phenotype in Stau2-deficient mice (deficits in spatial learning) is consistent with glutamatergic synapse function. Reason: STAU2 is likely present at glutamatergic synapses given its dendritic and postsynaptic localization, but specific enrichment at glutamatergic vs. other synapse types is not clearly established for the human protein. |
| GO:1900454 positive regulation of long-term synaptic depression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rat. LTD regulation could be an outcome of STAU2-mediated mRNA delivery and local translation at synapses. Reason: This is a specific downstream physiological consequence. The Stau2-deficient mouse shows altered synaptic plasticity-related behaviors, but direct evidence for LTD regulation specifically is from the rat ortholog. Supporting Evidence: PMID:29496644 Stau2GT mice displayed reduced locomotor activity in the open field and altered novelty preference in the NOR and NOL paradigms |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence data showing nucleoplasm localization. Consistent with STAU2's nucleocytoplasmic shuttling activity. Reason: Nuclear localization is well-established. STAU2 shuttles through the nucleus and a pool is present in neuronal nuclei. Supporting Evidence: PMID:15970630 A pool of Staufen2 is present in neuronal nuclei |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence showing cytosolic localization. STAU2 is a soluble cytoplasmic protein, consistent with cytosol localization. Reason: Cytosolic localization is the primary location. STAU2 is a soluble protein that assembles into RNP granules in the cytoplasm. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: STAU2 identified in NK cell membrane proteome. STAU2 has no transmembrane domain; its presence in membrane fractions likely reflects association of RNP granules with membranes or ER. Reason: STAU2 lacks transmembrane domains. Detection in membrane fractions is likely due to association of cytoplasmic RNP granules with the ER or other membrane compartments. This is a proteomics study of bulk membrane fractions. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: STAU2 identified in the mRNA interactome of HeLa cells by UV crosslinking and oligo(dT) purification. This is a genome-wide HDA confirmation of RNA binding. Reason: RNA binding is the fundamental molecular function of STAU2. The mRNA interactome capture provides high-throughput experimental confirmation. Supporting Evidence: PMID:22658674 We identify 860 proteins that qualify as RBPs |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: STAU2 identified in the mRNA-bound proteome by PAR-CLIP. Another genome-wide HDA confirmation of RNA binding. Reason: Confirms RNA binding by an independent method (PAR-CLIP vs. UV crosslinking). Supporting Evidence: PMID:22681889 Application to a human embryonic kidney cell line identified close to 800 proteins |
| GO:0003725 double-stranded RNA binding | IDA PMID:21266579 Raftlin is involved in the nucleocapture complex to induce p... | ACCEPT | Summary: STAU2 was pulled down on poly(I:C) affinity columns in a study of dsRNA-binding proteins involved in TLR3 activation. The poly(I:C) binding directly demonstrates dsRNA binding activity. Reason: Direct demonstration of dsRNA binding. poly(I:C) is a dsRNA analog, and affinity purification with poly(I:C) provides biochemical evidence of dsRNA binding. Supporting Evidence: PMID:21266579 we isolated poly(I:C)-binding proteins from CD14-negative cell lysates by sequential affinity chromatography with poly(U)- and poly(I:C)-Sepharose |
| GO:0003725 double-stranded RNA binding | TAS PMID:10585778 Identification of a novel homolog of the Drosophila staufen ... | ACCEPT | Summary: The original STAU2 identification paper described three dsRBDs. dsRNA binding is inferred from the domain architecture and sequence homology to Drosophila Staufen. Reason: The founding paper for STAU2 characterization. dsRNA binding is the canonical activity of the Staufen family proteins. Supporting Evidence: PMID:10585778 presence of three double-stranded RNA-binding domains |
| GO:0071598 neuronal ribonucleoprotein granule | ISS PMID:12140260 Staufen2 isoforms localize to the somatodendritic domain of ... | NEW | Summary: STAU2 is a component of neuronal RNA granules in dendrites, aligned on microtubule tracts. These granules are transport-competent RNP complexes that deliver mRNAs to synaptic sites. Falcon deep research corroborates that STAU2 localizes as RNP particles in the soma and dendrites. Reason: STAU2 is a well-established component of neuronal RNP granules. Duchaine et al. showed STAU2 in dendritic RNP complexes associated with microtubules. This term is more specific than the generic protein-containing complex annotation. Supporting Evidence: PMID:12140260 Stau2 is found in the somatodendritic compartment of neurons file:human/STAU2/STAU2-deep-research-falcon.md STAU2 localizes as **particles in soma and dendrites** |
| GO:0006402 mRNA catabolic process | IDA PMID:23263869 Staufen2 functions in Staufen1-mediated mRNA decay by bindin... | NEW | Summary: STAU2 participates in Staufen-mediated mRNA decay (SMD) by binding SBS-containing mRNAs and recruiting UPF1 helicase to promote mRNA degradation. STAU2 binds UPF1 ~10-fold more than STAU1. Falcon deep research corroborates that STAU2 can interact with itself and with STAU1 and promotes UPF1 helicase (but not ATPase) activity in SMD-related regulation. Reason: SMD is a well-characterized mRNA decay pathway mediated by both STAU1 and STAU2. Park et al. demonstrated STAU2 directly promotes UPF1 helicase activity for mRNA degradation. There is no specific GO term for SMD, so the parent term mRNA catabolic process is appropriate. Supporting Evidence: PMID:23263869 STAU2 binds ~10-fold more UPF1 file:human/STAU2/STAU2-deep-research-falcon.md **STAU2 can interact with itself and with STAU1** and can promote **UPF1 helicase (but not ATPase) activity** in SMD-related regulation |
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Download this section (compressed HTML)Q: What are the specific mRNA cargo differences between STAU1- and STAU2-containing RNP granules in human neurons, given that they do not colocalize?
Suggested experts: Michael A. Kiebler, Luc DesGroseillers
Q: Does STAU2 have specific roles at glutamatergic vs. GABAergic synapses, and is the positive regulation of LTD annotation from rat directly applicable to human?
Suggested experts: Michael A. Kiebler
Q: What is the functional significance of STAU2's interaction with EIF2AK2/PKR -- does STAU2 modulate innate immune dsRNA sensing, or is this merely reflecting shared dsRNA substrate recognition?
Suggested experts: Lynne E. Maquat
Experiment: Express individual STAU2 isoforms in STAU2-knockout neurons and assess dendritic mRNA transport (by MS2 live-cell imaging) and local translation (by puromycin incorporation or SunTag reporters) to determine isoform-specific functions.
Hypothesis: STAU2 has isoform-specific roles in neurons, with the 62 kDa isoform mediating mRNA transport and the 59/52 kDa isoforms mediating ribosome-associated functions.
Type: Live-cell imaging and translation reporter assays
Experiment: Measure SMD target mRNA half-lives in STAU2-knockdown vs. control neurons using actinomycin D chase experiments, comparing with UPF1 knockdown to distinguish SMD-dependent from SMD-independent effects.
Hypothesis: STAU2 participates in Staufen-mediated mRNA decay in neurons, distinct from its transport function.
Type: mRNA stability assay
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