Affinage

TAF15

Transcription initiation factor TFIID subunit 12 · UniProt Q16514

Length
161 aa
Mass
17.9 kDa
Annotated
2026-06-10
98 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAF15 is a multifunctional FET-family RNA/single-stranded-DNA-binding protein that couples transcription to RNA processing and, in disease, becomes the principal amyloid-forming species in frontotemporal lobar degeneration (PMID:8890175, PMID:38057661). It was first isolated as a TBP-associated factor that co-purifies with a subpopulation of TFIID and enters the RNA polymerase II preinitiation complex, binding both RNA and ssDNA through a consensus RNA-binding domain (PMID:8890175, PMID:9488465). Its RRM engages target RNAs through a non-canonical hydrogen-bonding mode that reads RNA stem-loop structure rather than sequence alone (PMID:26612539), and transcriptome-wide it binds thousands of structured, GGUA-enriched transcripts—enriched for synaptic mRNAs—where it controls RNA turnover and a specific Grin1 alternative-splicing event, while contributing minimally to global splicing (PMID:23416048, PMID:27378374). TAF15 assembles into homo- and hetero-complexes with FUS and EWSR1 via a conserved, RNA-independent N-terminal FETBM1 motif (PMID:23975937), and a fraction associates with U1 snRNP through direct contact with U1C to form a distinct U1-TAF15 snRNP (PMID:19282884, PMID:22019700). Its activity is governed by extensive post-translational modification of the RGG-rich C-terminal low-complexity domain: PRMT1-mediated arginine methylation regulating shuttling and target-gene activation (PMID:19124016), Src tyrosine phosphorylation enhancing transcriptional activation (PMID:15094065), and PKA serine phosphorylation that retunes RNA-binding specificity (PMID:38568213). The same low-complexity domain phase-separates and forms amyloid-like fibrils that bind the RNA polymerase II CTD through electrostatic contacts with heptad-position lysines (PMID:28945358, PMID:41085196). In FTLD, TAF15 low-complexity-domain residues 7–99 fold into structurally defined amyloid filaments that are identical across patients, establishing TAF15 rather than FUS as the primary pathological aggregate in FTLD-TAF15 (PMID:38057661). TAF15 also functions as a sequence-specific promoter-binding transcriptional activator in cancer and metabolic contexts, driving FASN, SOCS1, and NF-κB-dependent programs (PMID:37183512, PMID:41244301).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1996 High

    Establishing TAF15's biochemical identity answered whether it was a transcription factor, showing it is a TBP-associated factor bridging TFIID and Pol II that also binds nucleic acids.

    Evidence Biochemical co-purification with TFIID and Pol II plus RNA/ssDNA binding assays

    PMID:8890175

    Open questions at the time
    • Did not define which promoters or genes depend on TAF15
    • RNA-binding specificity unresolved
  2. 1998 High

    Mapping TAF15 and EWS contacts within TFIID addressed how FET proteins partition among basal machinery, indicating mutually exclusive incorporation into TFIID.

    Evidence In vitro binding assays and Co-IP with defined TFIID and Pol II subunits

    PMID:9488465

    Open questions at the time
    • Functional consequence of mutual exclusivity untested
    • Stoichiometry in vivo unknown
  3. 2008 Medium

    Localization and methylation studies addressed how TAF15 trafficking is controlled, identifying PRMT1 as the RGG arginine methyltransferase that governs nucleocytoplasmic shuttling and target-gene activation, and placing TAF15 in stress granules.

    Evidence Immunofluorescence/fractionation across cell types; Co-IP, in vitro methylation, gene expression after PRMT1 perturbation

    PMID:18620564 PMID:19124016

    Open questions at the time
    • Specific methylated arginines not all mapped
    • Link between methylation and stress-granule recruitment unclear
  4. 2009 High

    Discovery of a U1-TAF15 snRNP and caspase cleavage addressed how TAF15 connects to splicing machinery and apoptotic regulation, defining a non-canonical chromatin-associated U1 particle and a caspase-3/7 cleavage site.

    Evidence RNA-IP, chromatin fractionation, U1 mutagenesis; in vitro caspase cleavage with site-directed mutagenesis

    PMID:19282884 PMID:19426707

    Open questions at the time
    • Function of the U1-TAF15 snRNP not established
    • Biological role of caspase cleavage fragment unknown
  5. 2011 Medium

    FTLD fractionation and the U1C interaction addressed the disease relevance and spliceosomal coupling of TAF15, showing FET-protein insolubility in FTLD-FUS and a direct N-terminal TAF15–U1C contact.

    Evidence Post-mortem tissue immunoblot, Transportin-inhibition cell models; reciprocal Co-IP, recombinant pulldown, UV crosslinking

    PMID:21856723 PMID:22019700

    Open questions at the time
    • Whether TAF15 or FUS is the primary aggregate not yet resolved in 2011
    • Direct RNA targets in vivo incompletely defined
  6. 2012 Medium

    Domain mapping and the miR-17/CDKN1A work addressed how TAF15 controls its own localization and cell proliferation, defining a C-terminal transportin-dependent NLS and a post-transcriptional growth-control axis.

    Evidence GFP-fusion domain deletions with transportin/transcription inhibition; siRNA knockdown with gene/miRNA profiling and proliferation assays

    PMID:22771914 PMID:23128393

    Open questions at the time
    • Mechanism by which TAF15 controls miR-17 locus unknown
    • Cell-type-specific localization rules not generalized
  7. 2013 High

    CLIP-based target identification and FET heterocomplex mapping addressed what RNAs TAF15 regulates and how FET proteins assemble, defining synaptic-transcript binding, a specific Grin1 splicing role, and the RNA-independent FETBM1 interaction motif.

    Evidence HITS-CLIP, RNA-seq, neuronal knockdown; recombinant pulldown, mass spectrometry, FETBM1 mutagenesis

    PMID:23416048 PMID:23975937

    Open questions at the time
    • Functional significance of most bound transcripts untested
    • Whether FET heterocomplexes act in transcription or RNA processing not separated
  8. 2014 Medium

    The hnRNP M isoform-selective interaction addressed how individual FET proteins acquire distinct partnerships, showing TAF15 preferentially binds hnRNP M3/4 via its amino-terminus.

    Evidence Co-IP, recombinant pulldown, immunofluorescence co-localization

    PMID:24474660

    Open questions at the time
    • Functional outcome of the TAF15–hnRNP M complex unknown
    • Single lab without reciprocal in vivo validation
  9. 2015 High

    The RRM solution structure addressed the molecular basis of TAF15 RNA recognition, revealing a non-canonical hydrogen-bonding interface that reads RNA structure rather than sequence.

    Evidence Solution NMR, ITC, docking and molecular dynamics

    PMID:26612539

    Open questions at the time
    • In vivo relevance of structure-based recognition not tested
    • Contribution of RGG domain to RNA affinity not modeled here
  10. 2016 High

    Genome-wide binding in brain addressed TAF15's transcriptome-scale function, confirming GGUA-motif binding, 3'UTR enrichment, RNA-turnover control shared with FUS, and minimal splicing role.

    Evidence CLIP-seq, RNA Bind-N-Seq, RNA-seq, double knockout

    PMID:27378374

    Open questions at the time
    • Mechanism linking binding to turnover unresolved
    • Redundancy boundaries with FUS not fully mapped
  11. 2017 High

    LC-domain fibril and PRMT1-selectivity studies addressed how TAF15 engages the Pol II CTD and why it is hypomethylated, defining electrostatic CTD-lysine contacts and a methylation-limiting Asp in its RGG repeats.

    Evidence NMR, hydrogel fibril FRAP, CTD lysine mutagenesis; peptide polyRGG assays and 2-hybrid binding

    PMID:28945358 PMID:29193371

    Open questions at the time
    • Whether CTD-fibril binding occurs at native concentrations in cells untested
    • Consequence of reduced methylation for TAF15 function not directly shown
  12. 2018 Medium

    Src phosphorylation and Drosophila parkin work addressed signaling control and turnover of TAF15, showing tyrosine phosphorylation enhances transcriptional activation and parkin ubiquitin-ligase activity lowers TAF15 levels and toxicity.

    Evidence In vitro kinase and SH3 Co-IP with reporter assays; Drosophila Co-IP, genetic rescue, protein-level westerns

    PMID:15094065 PMID:30339961

    Open questions at the time
    • Phosphorylated residues and direct transcriptional mechanism not mapped
    • Parkin–TAF15 relationship not confirmed in mammalian neurons
  13. 2020 Medium

    GSK-3β/SCF-Slimb genetics addressed the degradation pathway controlling TAF15 toxicity, showing kinase activation and an E3 ligase complex modulate TAF15 levels and neurotoxicity.

    Evidence Transgenic Drosophila, lithium inhibition, F-box epistasis, westerns and immunohistochemistry

    PMID:32915460

    Open questions at the time
    • Direct phosphorylation of TAF15 by GSK-3β not demonstrated
    • Mammalian relevance untested
  14. 2021 Medium

    Xenopus depletion addressed TAF15's developmental role, showing it regulates a single target (fgfr4) through both intron retention and transcript-abundance control during neural development.

    Evidence Morpholino/CRISPR depletion, RNA-seq exon/abundance analysis, epistasis

    PMID:34345915

    Open questions at the time
    • Whether dual regulation generalizes beyond fgfr4 unknown
    • Ortholog-specific; mammalian developmental role untested
  15. 2022 Medium

    SRPK1, TIF1γ, and PrLD aggregation studies addressed how TAF15 modulates splicing kinases, how it is competitively regulated at TBP, and what drives its aggregation, defining SRPK1 inhibition, TIF1γ-mediated ubiquitylation/export, and an SGYS β-amyloid motif sensitized by ALS mutation E71G.

    Evidence Co-IP, kinase and splicing-reporter assays; ubiquitylation, fractionation, IL-6 reporter, EMT assays; ThT aggregation, MD, phase-separation microscopy

    PMID:35643629 PMID:36261009 PMID:36611919

    Open questions at the time
    • Physiological balance between TAF15 activator and SRPK1-inhibitor roles unclear
    • Whether SGYS-driven aggregation matches ex vivo filament core not yet linked
  16. 2023 High

    Cryo-EM of patient filaments and oncogenic transcription studies resolved the disease-defining question and expanded TAF15's promoter-bound activator role, establishing TAF15 LCD residues 7–99 as the FTLD amyloid fold and showing direct activation of FASN, SOCS1, and NF-κB programs.

    Evidence Cryo-EM of ex vivo brain filaments; CUT&Tag, luciferase, Co-IP, CRISPR KO and in vivo mouse/cell models

    PMID:37183512 PMID:38057661 PMID:41244301

    Open questions at the time
    • Trigger converting soluble TAF15 to filaments in vivo unknown
    • Sequence specificity of promoter binding not structurally defined
  17. 2024 Medium

    PKA phosphorylation and CypA stabilization addressed additional control of TAF15 RNA-binding and stability, showing PKA retunes transcript binding and CypA suppresses proteasomal degradation while promoting nuclear localization.

    Evidence iCLIP with cAMP activation; Co-IP, MS, proteasome inhibition, fractionation

    PMID:38568213 PMID:39402372

    Open questions at the time
    • Phosphosites and direct downstream functional effects not mapped
    • CypA/TAF15 loop validated in single cancer context
  18. 2025 Medium

    Phase-separation/hnRNPA0 and prion-propagation studies addressed how the LC domain links condensate formation to transcription and disease spread, showing the C-terminal LCD is necessary and sufficient for hnRNPA0-enhanced transcription and that TAF15 fibrils seed and propagate FUS-independently.

    Evidence Domain swaps, phosphomimic and ALS mutations, transcription/phase-separation assays; recombinant fibrils, biosensor propagation, patient-brain seeding (preprint)

    PMID:41085196 PMID:bio_10.1101_2025.11.17.688886

    Open questions at the time
    • In vivo relevance of hnRNPA0 condensates untested
    • Prion-propagation evidence remains a preprint without peer review
  19. 2026 Low

    FET redundancy imaging and expanded cryo-EM addressed TAF15's homeostatic and structural disease spectrum, showing TAF15 compensates for EWSR1 loss at nascent RNA and that multiple TAF15 filament folds, including a Y38C-variant-driven fold, define FTLD-FET subtypes.

    Evidence Acute EWSR1 depletion with nanoscale imaging (preprint); cryo-EM of 17 patient brains with genetic sequencing (preprint)

    PMID:41648099 PMID:42051291

    Open questions at the time
    • EWSR1-compensation finding is imaging-based inference in a single preprint
    • Functional impact of distinct filament folds on clinical phenotype unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological trigger that converts soluble, modification-regulated TAF15 into self-propagating amyloid filaments in human neurons, and how its transcription, RNA-processing, and condensate functions are integrated, remain unresolved.
  • No defined in vivo nucleation trigger for filament formation
  • Mechanistic link between normal RNA/transcription roles and pathological aggregation unestablished
  • Therapeutic strategies targeting TAF15 aggregation untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003723 RNA binding 5 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005634 nucleus 4 GO:0005730 nucleolus 2 GO:0005829 cytosol 2 GO:0005694 chromosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 3
Partners
CYPAEWSR1FUSHNRNPA0PRMT1SRPK1TBPU1C
Complex memberships
FET heterocomplex (FUS/EWSR1/TAF15)RNA polymerase II preinitiation complexTFIIDU1-TAF15 snRNP

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 TAF15 (hTAFII68) was identified as a novel TBP-associated factor that co-purifies with a subpopulation of TFIID complexes and also co-purifies with RNA polymerase II, entering the preinitiation complex together with Pol II. The protein contains a consensus RNA-binding domain (RNP-CS) and binds both RNA and single-stranded DNA. Biochemical co-purification, RNA/ssDNA binding assays The EMBO journal High 8890175
1998 TAF15 (hTAFII68) interacts with specific TFIID subunits and specific subunits of RNA polymerase II. In vitro binding studies showed EWS and TAF15 interact with the same TFIID subunits, suggesting their presence in the same TFIID complex is mutually exclusive. In vitro binding assays, co-immunoprecipitation from nuclear extracts Molecular and cellular biology High 9488465
2008 TAF15 is present in both the nucleus and cytoplasm of most cell types. FET proteins (including TAF15) are targeted to stress granules induced by heat shock and oxidative stress. TAF15 (and FUS) were also detected in spreading initiation centers of adhering cells. Immunofluorescence, subcellular fractionation, live-cell imaging in multiple human cell types BMC cell biology Medium 18620564
2008 Endogenous TAF15 is methylated in vivo at its RGG repeats by PRMT1. PRMT1 was identified as a TAF15-interacting protein and the major PRMT responsible for this methylation. Methylation of the RGG-containing C-terminus affects TAF15 subcellular localization (nucleus-cytoplasm shuttling) and is required for TAF15 to positively regulate expression of its target genes. Co-immunoprecipitation, in vitro methylation assay, subcellular fractionation, gene expression analysis after PRMT1 inhibition/knockdown Experimental cell research High 19124016
2009 A fraction of TAF15 specifically associates with human U1 snRNA to form a novel U1-TAF15 snRNP that is distinct from the canonical spliceosomal U1-Sm snRNP (none of the known Sm or U1-specific proteins co-precipitate). The U1-TAF15 snRNP tightly associates with chromatin in an RNA-dependent manner and accumulates in nucleolar caps upon transcriptional inhibition. The Sm-binding motif of U1 snRNA is essential for biogenesis of both U1-Sm and U1-TAF15 snRNPs. RNA immunoprecipitation, chromatin fractionation, transcription inhibition experiments, mutational analysis of U1 snRNA EMBO reports High 19282884
2011 In FTLD-FUS (but not ALS-FUS-mutation cases), all endogenous FET proteins including TAF15 and EWS shift to insoluble fractions. Cell culture experiments showed that inhibition of Transportin-mediated nuclear import recruits all endogenous FET proteins (including TAF15) into cytoplasmic stress granules, mimicking the FTLD finding. Immunoblot of post-mortem tissue fractions, cell culture experiments with Transportin inhibition, immunohistochemistry Brain : a journal of neurology Medium 21856723
2011 A fraction of nuclear TAF15 associates with the spliceosomal U1 snRNP complex, as demonstrated by co-precipitation of U1 snRNA, U1-70K, and Sm proteins. Pull-down assays showed a direct protein-protein interaction between TAF15 and U1C that required the N-terminal domain of TAF15. In vivo UV cross-linking showed TAF15 directly contacts RNA (likely Pol II transcripts). Immunoprecipitation from HeLa nuclear extracts, pull-down with recombinant proteins, UV cross-linking Biochimica et biophysica acta Medium 22019700
2012 TAF15 knockdown affects expression of genes involved in cell cycle and apoptosis, causes growth inhibition and increased apoptosis. TAF15 regulates cell cycle genes post-transcriptionally through a pathway involving miRNAs from the onco-miR-17 locus (miR-17-5p and miR-20a), which in turn control CDKN1A/p21 levels. TAF15 depletion decreases levels of miR-17-5p and miR-20a. siRNA knockdown, global gene expression profiling, miRNA quantification, cell proliferation/apoptosis assays Oncogene Medium 23128393
2012 The C-terminal RGG domain of TAF15 is responsible for shuttling between the nucleus and cytoplasm. A transportin-dependent nuclear localization signal (NLS) resides at the C-terminus. TAF15 localization was shown to depend on ongoing transcription, and independent domains engage in nucleolar capping upon transcription inhibition. TAF15 localization is differentially regulated in HeLa versus neuronal HT22 cells. Domain deletion constructs, GFP fusions, transportin inhibition assays, transcription inhibition experiments, subcellular fractionation Gene Medium 22771914
2013 TAF15 binds to conserved RNA targets in human brain and mouse neurons enriched in transcripts encoding synaptic proteins. TAF15 is required for a critical alternative splicing event of the Grin1 (NMDA receptor NR1 subunit) that controls NR1 activity and trafficking. Unlike FUS and TDP-43, TAF15 has a minimal role in general alternative splicing. HITS-CLIP, RNA-seq, siRNA knockdown in neurons, splicing analysis Cell reports High 23416048
2013 FUS, EWSR1, and TAF15 form homo- and heterocomplexes via a conserved N-terminal motif (FETBM1). This interaction is RNA- and DNA-independent and robust up to 1M NaCl. The FETBM1 motif is also required for binding of normal full-length FET proteins to their oncogenic fusion proteins. Recombinant protein pulldown, mass spectrometry, mutagenesis of FETBM1 motif FASEB journal High 23975937
2014 TAF15 selectively co-immunoprecipitates with the higher molecular weight hnRNP M3/4 isoforms (contrasting with FUS which prefers hnRNP M1/2). This association is mediated through direct protein-protein interactions via the amino-termini of the TET proteins, independently of RNA. Co-immunoprecipitation from HeLa nuclear extracts, recombinant protein pulldown, immunofluorescence co-localization Molecular biology reports Medium 24474660
2015 The solution NMR structure of the TAF15 RRM domain was determined. RNA binding occurs through a non-canonical mode: rather than classical stacking interactions between nitrogen bases and aromatic amino acids at RNP sites, moderate-affinity hydrogen bonding between stem-loop RNA bases and a concave face on the RRM surface primarily mediates the interaction. RNA binding depends on structural elements in the RNA rather than sequence alone. Solution NMR spectroscopy, isothermal titration calorimetry, docking, molecular dynamics simulation Scientific reports High 26612539
2016 TAF15 binds ~4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns and are enriched in 3' UTRs. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. Unlike FUS and TDP-43, TAF15 has minimal role in alternative splicing. CLIP-seq, RNA Bind-N-Seq, RNA-seq in motor neurons and neural progenitors, double KO analysis Nature communications High 27378374
2017 TAF15 low-complexity (LC) domain forms amyloid-like hydrogel fibrils that bind the CTD of RNA polymerase II. NMR and FRAP showed that heptad positions far from the acidic C-terminal tail of RNA pol II CTD bind TAF15 fibrils most avidly. Mutation of CTD lysines at heptad position 7 to consensus serines reduced TAF15 fibril binding, implicating electrostatic interactions in complex formation. NMR spectroscopy (spin relaxation, dark-state exchange saturation transfer), hydrogel fibril FRAP assay, site-directed mutagenesis of CTD lysines Biochemistry High 28945358
2017 PRMT1 shows differential interaction with RGG-boxes of TAF15 compared to FUS and EWS. The Asp residue in TAF15's YGGDR(S/G)G repeats confers poor binding to PRMT1, resulting in reduced overall methylation of TAF15 compared to other FET proteins. Peptide-based polyRGG substrate assays, novel 2-hybrid binding assay Protein science Medium 29193371
2018 TAF15 is phosphorylated on tyrosine residue(s) by v-Src kinase in vitro and in vivo. TAF15 associates with the SH3 domains of v-Src and other cell signaling proteins. Full-length v-Src stimulates TAF15-mediated transcriptional activation, while dominant-negative Src reduces it in a dose-dependent fashion. In vitro kinase assay, co-immunoprecipitation with SH3 domains, transcriptional reporter assays, dominant-negative overexpression FEBS letters Medium 15094065
2018 In a Drosophila model, parkin directly binds to TAF15. Parkin overexpression suppresses TAF15-induced toxicity (defective lifespan and locomotion), and overexpression of parkin in neuronal cells reduces TAF15 protein levels through parkin's E3 ubiquitin ligase activity. Co-immunoprecipitation in Drosophila, genetic overexpression/loss-of-function, western blot quantification of TAF15 levels Neurobiology of aging Medium 30339961
2020 GSK-3β (Shaggy) is abnormally activated in neurons of TAF15-expressing Drosophila. GSK-3β inhibition (pharmacological or genetic) reduces TAF15 protein levels and suppresses TAF15-induced neurotoxicity. The SCF-Slimb E3 ubiquitin ligase complex genetically interacts with TAF15 and is critical for GSK-3β-mediated suppression of TAF15 toxicity. Transgenic Drosophila model, pharmacological GSK-3β inhibition (lithium), genetic epistasis with F-box proteins, western blot, immunohistochemistry Journal of neurochemistry Medium 32915460
2021 In Xenopus tropicalis, Taf15 regulates dorsoanterior neural development through two distinct mechanisms on a single target fgfr4: (1) maternal+zygotic Taf15 depletion causes intron retention in fgfr4, and (2) depletion of zygotic Taf15 alone reduces total fgfr4 transcript levels, indicating both post-transcriptional and transcriptional modes of regulation. Morpholino/CRISPR depletion in Xenopus, RNA-seq for exon usage and transcript abundance, epistasis with fgfr4 and ventx2.1 Development (Cambridge, England) Medium 34345915
2022 The C-terminal RGG domain of TAF15 associates with SRPK1, downregulates SRPK1 kinase activity, partially relocalizes SRPK1 to the nucleus, and results in hypophosphorylation of SR proteins, inhibition of pre-mRNA splicing of a reporter minigene, and inhibition of Lamin B receptor phosphorylation. Co-immunoprecipitation, kinase activity assay, reporter minigene splicing assay, western blot for SR protein phosphorylation, fluorescence microscopy Cells Medium 36611919
2022 TIF1γ binds TBP in competition with TAF15 and impedes TAF15/TBP-mediated IL-6 transactivation. TIF1γ modifies TAF15 through multi-mono-ubiquitylation and drives nuclear export of TAF15. TAF15/TBP complex activity is required for IL-6 activation-induced EMT and invasion of lung adenocarcinoma cells. Co-immunoprecipitation in human cell lines, ubiquitylation assay, nuclear/cytoplasmic fractionation, luciferase reporter for IL-6 transactivation, EMT/invasion assays Cell reports Medium 36261009
2022 The SGYS motif within the TAF15 prion-like domain (PrLD) is a critical segment for amyloid fibril formation. ALS-associated mutation E71G in the T2 segment (Y56GQSQSGYSQSYGGYENQ73) significantly enhances aggregation. The T2 peptide with strong β-amyloid-forming tendency can induce liquid-to-solid phase transition of TAF15-PrLD protein. The SGYS motif maintains a stable β-sheet through intermolecular hydrogen bonds and π-π stacking. Thioflavin T aggregation assay, molecular dynamics simulation, mutagenesis, phase separation microscopy Biophysical journal Medium 35643629
2023 Cryo-EM structures of TAF15 amyloid filaments extracted from FTLD-FUS patient brains were determined. The filament fold is formed from residues 7–99 in the low-complexity domain (LCD) of TAF15, was identical among four individuals, and the same fold was found in motor cortex and brainstem of two individuals with upper/lower motor neuron pathology. This establishes TAF15 (not FUS) as the primary amyloid-forming protein in FTLD-FUS (now FTLD-TAF15). Cryo-electron microscopy of ex vivo amyloid filaments from post-mortem human brain Nature High 38057661
2023 TAF15 directly binds the promoter region of FASN to facilitate its transcription, promoting lipid steatosis. TAF15 also interacts with p65 (NF-κB subunit) and activates NF-κB signaling, increasing proinflammatory cytokine secretion and triggering M1 macrophage polarization. Both effects were shown in hepatocyte-specific AAV-knockdown and overexpression mouse models of NASH. CUT&Tag, dual-luciferase reporter assay, co-immunoprecipitation, immunofluorescence, hepatocyte-specific AAV knockdown/overexpression in mice Liver international Medium 37183512
2023 TAF15 in tumor-associated macrophages transcriptionally activates SOCS1, thereby inhibiting the JAK2/STAT1 signaling pathway and suppressing M1 macrophage polarization, promoting M2 polarization and ICC progression. CUT&Tag, dual-luciferase reporter assay, CRISPR-Cas9 TAF15 knockout in THP-1 cells, in vitro co-culture, in vivo M2pepLNP-siTAF15 treatment JHEP reports Medium 41244301
2024 TAF15 is a nuclear substrate of PKA. PKA-mediated phosphorylation of TAF15 alters its binding to target transcripts related to mRNA maturation, splicing, and protein-binding functions, as shown by iCLIP experiments comparing phosphorylated vs. unphosphorylated TAF15. iCLIP (crosslinking immunoprecipitation), PKA substrate identification, cAMP pathway activation Cellular and molecular life sciences Medium 38568213
2024 CypA interacts with TAF15, stabilizes it by suppressing proteasomal degradation, and promotes its nuclear localization. TAF15 in turn positively regulates STAT5A. This forms a CypA/TAF15/STAT5A/miR-514a-3p feedback loop driving EMT in ovarian cancer. Co-immunoprecipitation, mass spectrometry, proteasome inhibition assay, subcellular fractionation, western blot Oncogene Medium 39402372
2025 TAF15's C-terminal low-complexity (LC) domain undergoes phase separation and mediates dynamic interactions with hnRNPA0, which enhances TAF15's transcriptional activity. Domain-swapping with FUS showed the C-terminal LC domain is both necessary and sufficient for hnRNPA0 responsiveness. Phosphomimic mutations in the C-terminal LC domain disrupt hnRNPA0 interaction. ALS-linked mutations in TAF15 impair phase separation, reduce hnRNPA0 binding, and eliminate transcriptional enhancement. Domain-swap experiments, phosphomimic mutagenesis, ALS-linked point mutations, transcriptional reporter assays, phase separation microscopy FASEB journal Medium 41085196
2009 TAF15 is specifically cleaved by caspases-3 and -7 at the consensus sequence 106DQPD/Y110. Site-directed mutagenesis confirmed this as the sole caspase-3/7 cleavage site. TAF15 was cleaved at more than one site in staurosporine-treated Jurkat cells, suggesting additional proteolytic regulation in apoptosis. In vitro caspase cleavage assay, site-directed mutagenesis, cell-based apoptosis assay Biochemical and biophysical research communications Medium 19426707
2025 TAF15 forms amyloid fibrils under physiological conditions that propagate in a prion-like fashion between cells. Patient-derived TAF15 aggregates from aFTLD-U brains seed aggregation and transmit serially between cells. Seeding is specific to TAF15 and does not cross-seed with FUS. Computational and peptide mapping identified multiple aggregation-prone regions in the TAF15 low-complexity domain that coincide with ex vivo filament core hotspots. Recombinant fibril formation, single-fluorophore biosensor for cellular propagation, patient brain extract seeding, peptide aggregation mapping, computational prediction bioRxivpreprint Medium bio_10.1101_2025.11.17.688886
2026 Acute depletion of EWSR1 induces compensatory reorganization of both FUS and TAF15 to closely resemble EWSR1's organization with nascent RNA, demonstrating functional redundancy within the FET family for homeostatic regulation of nascent RNA levels. Nanoscale imaging showed TAF15 redistributes to enhance clustering with newly synthesized RNA upon EWSR1 loss. Acute EWSR1 depletion, nanoscale fluorescence imaging, nascent RNA labeling bioRxivpreprint Low 42051291
2026 All three proposed subtypes of FTLD-FET (aFTLD-U, NIFID, BIBD) are characterized by TAF15 amyloid filaments (not FUS filaments). Four distinct TAF15 filament folds were identified among NIFID cases and distinct folds for BIBD cases. A TAF15 Y38C variant was found in one BIBD case whose filament fold cannot incorporate wild-type TAF15 despite heterozygosity, suggesting this variant drives TAF15 filament assembly. Cryo-EM structure determination from post-mortem brain tissue of 17 individuals; genetic sequencing bioRxivpreprint Medium 41648099

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 hTAF(II)68, a novel RNA/ssDNA-binding protein with homology to the pro-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II. The EMBO journal 299 8890175
2008 The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC cell biology 275 18620564
2011 FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutations. Brain : a journal of neurology 245 21856723
1998 EWS, but not EWS-FLI-1, is associated with both TFIID and RNA polymerase II: interactions between two members of the TET family, EWS and hTAFII68, and subunits of TFIID and RNA polymerase II complexes. Molecular and cellular biology 227 9488465
2011 Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 146 21438137
2016 Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. Nature communications 140 27378374
1999 Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma. Cancer research 115 10537274
2010 Dr. Jekyll and Mr. Hyde: The Two Faces of the FUS/EWS/TAF15 Protein Family. Sarcoma 113 21197473
2002 Recurrent rearrangement of the Ewing's sarcoma gene, EWSR1, or its homologue, TAF15, with the transcription factor CIZ/NMP4 in acute leukemia. Cancer research 100 12359745
1999 Identification of a novel fusion gene involving hTAFII68 and CHN from a t(9;17)(q22;q11.2) translocation in an extraskeletal myxoid chondrosarcoma. Oncogene 85 10602520
1998 Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes. Gene 85 9795213
2008 PRMT1 mediated methylation of TAF15 is required for its positive gene regulatory function. Experimental cell research 80 19124016
1999 Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11). Oncogene 65 10602519
2020 lncRNA LINC00665 Stabilized by TAF15 Impeded the Malignant Biological Behaviors of Glioma Cells via STAU1-Mediated mRNA Degradation. Molecular therapy. Nucleic acids 57 32464546
1996 Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins. Genomics 57 8954779
2009 Human U1 snRNA forms a new chromatin-associated snRNP with TAF15. EMBO reports 56 19282884
2012 TAF15 is important for cellular proliferation and regulates the expression of a subset of cell cycle genes through miRNAs. Oncogene 53 23128393
2024 Insights into Molecular Diversity within the FUS/EWS/TAF15 Protein Family: Unraveling Phase Separation of the N-Terminal Low-Complexity Domain from RNA-Binding Protein EWS. Journal of the American Chemical Society 49 38492239
2019 TRPM2-AS promotes cancer cell proliferation through control of TAF15. The international journal of biochemistry & cell biology 43 31887411
2021 LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers. Laboratory investigation; a journal of technical methods and pathology 42 33875793
2020 LncRNA PITPNA-AS1 boosts the proliferation and migration of lung squamous cell carcinoma cells by recruiting TAF15 to stabilize HMGB3 mRNA. Cancer medicine 42 32871048
2019 USF1-induced upregulation of LINC01048 promotes cell proliferation and apoptosis in cutaneous squamous cell carcinoma by binding to TAF15 to transcriptionally activate YAP1. Cell death & disease 42 30931936
2023 TAF15 amyloid filaments in frontotemporal lobar degeneration. Nature 41 38057661
2013 A conserved N-terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 39 23975937
2012 Domains involved in TAF15 subcellular localisation: dependence on cell type and ongoing transcription. Gene 38 22771914
2013 Identification of in vivo, conserved, TAF15 RNA binding sites reveals the impact of TAF15 on the neuronal transcriptome. Cell reports 37 23416048
2017 Lysines in the RNA Polymerase II C-Terminal Domain Contribute to TAF15 Fibril Recruitment. Biochemistry 36 28945358
2019 NR4A3 fusion proteins trigger an axon guidance switch that marks the difference between EWSR1 and TAF15 translocated extraskeletal myxoid chondrosarcomas. The Journal of pathology 30 31020999
2011 Identification of the TAF15-ZNF384 fusion gene in two new cases of acute lymphoblastic leukemia with a t(12;17)(p13;q12). Cancer genetics 29 21504714
2022 TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex. Cell reports 26 36261009
2016 α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15. Scientific reports 26 27181033
2011 mRNA and protein levels of FUS, EWSR1, and TAF15 are upregulated in liposarcoma. Genes, chromosomes & cancer 26 21344536
2023 CircDNAJC11 interacts with TAF15 to promote breast cancer progression via enhancing MAPK6 expression and activating the MAPK signaling pathway. Journal of translational medicine 25 36895010
2011 A fraction of the transcription factor TAF15 participates in interactions with a subset of the spliceosomal U1 snRNP complex. Biochimica et biophysica acta 24 22019700
2021 LncRNA APOA1-AS facilitates proliferation and migration and represses apoptosis of VSMCs through TAF15-mediated SMAD3 mRNA stabilization. Cell cycle (Georgetown, Tex.) 22 34382908
2023 m6A-enriched lncRNA LINC00839 promotes tumor progression by enhancing TAF15-mediated transcription of amine oxidase AOC1 in nasopharyngeal carcinoma. The Journal of biological chemistry 20 37257820
2023 TAF15 exacerbates nonalcoholic steatohepatitis progression by regulating lipid metabolism and inflammation via FASN and p65 NF-κB. Liver international : official journal of the International Association for the Study of the Liver 19 37183512
2023 Epigallocatechin gallate prevents cardiomyocytes from pyroptosis through lncRNA MEG3/TAF15/AIM2 axis in myocardial infarction. Chinese medicine 18 38057891
2022 LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway. Cancer gene therapy 18 35228660
2021 STAT1 mediated long non-coding RNA LINC00504 influences radio-sensitivity of breast cancer via binding to TAF15 and stabilizing CPEB2 expression. Cancer biology & therapy 18 34908514
2004 Stimulation of hTAFII68 (NTD)-mediated transactivation by v-Src. FEBS letters 18 15094065
2020 TAF15 contributes to the radiation-inducible stress response in cancer. Oncotarget 17 32676166
2010 Diagnostic and therapeutic potential of a human antibody cloned from a cancer patient that binds to a tumor-specific variant of transcription factor TAF15. Cancer research 17 20048082
2022 Exosomes from artesunate-treated bone marrow-derived mesenchymal stem cells transferring SNHG7 to promote osteogenesis via TAF15-RUNX2 pathway. Regenerative medicine 16 36184881
2022 Long non-coding RNA SNHG4 enhances RNF14 mRNA stability to promote the progression of colorectal cancer by recruiting TAF15 protein. Apoptosis : an international journal on programmed cell death 15 36482019
2020 miR-182-5p inhibits the pathogenic Th17 response in experimental autoimmune uveitis mice via suppressing TAF15. Biochemical and biophysical research communications 15 32736708
2023 TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression. Regenerative therapy 13 37496731
2015 Structural delineation of stem-loop RNA binding by human TAF15 protein. Scientific reports 13 26612539
2023 TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway. Scientific reports 12 37037864
2022 LncRNA HOTTIP facilitates osteogenic differentiation in bone marrow mesenchymal stem cells and induces angiogenesis via interacting with TAF15 to stabilize DLX2. Experimental cell research 12 35644412
2022 LncRNA MIR9-3HG enhances LIMK1 mRNA and protein levels to contribute to the carcinogenesis of lung squamous cell carcinoma via sponging miR-138-5p and recruiting TAF15. Pathology, research and practice 12 35933883
2021 lncRNA PAPPA-AS1 Induces the Development of Hypertrophic Scar by Upregulating TLR4 through Interacting with TAF15. Mediators of inflammation 11 34285657
2017 Differential interaction of PRMT1 with RGG-boxes of the FET family proteins EWS and TAF15. Protein science : a publication of the Protein Society 11 29193371
2023 Extraskeletal Myxoid Chondrosarcomas: The Uncommon Clinicopathologic Manifestations and Significance of TAF15::NR4A3 Fusion. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 10 36948401
2023 TAF15::NR4A3 gene fusion identifies a morphologically distinct subset of extraskeletal myxoid chondrosarcoma mimicking myoepithelial tumors. Genes, chromosomes & cancer 10 37057757
2023 lncRNA GMDS-AS1 restrains lung adenocarcinoma progression via recruiting TAF15 protein to stabilize SIRT1 mRNA. Epigenomics 10 37309595
2022 Octreotide ameliorates hepatic ischemia-reperfusion injury through SNHG12/TAF15-mediated Sirt1 stabilization and YAP1 transcription. Toxicology and applied pharmacology 10 35307376
2016 Mixed Phenotype Acute Leukemia with t(12;17)(p13;q21)/TAF15-ZNF384 and Other Chromosome Abnormalities. Cytogenetic and genome research 10 27607436
2014 Selective interactions of hnRNP M isoforms with the TET proteins TAF15 and TLS/FUS. Molecular biology reports 10 24474660
2011 Characterization and expression analysis in the developing embryonic brain of the porcine FET family: FUS, EWS, and TAF15. Gene 10 22143032
2022 YY1-induced lncRNA XIST inhibits cartilage differentiation of BMSCs by binding with TAF15 to stabilizing FUT1 expression. Regenerative therapy 9 35402663
2024 CypA/TAF15/STAT5A/miR-514a-3p feedback loop drives ovarian cancer metastasis. Oncogene 8 39402372
2022 Identification of a novel translocation producing an in-frame fusion of TAF15 and ETV4 in a case of extraosseous Ewing sarcoma revealed in the prenatal period. Virchows Archiv : an international journal of pathology 8 35527322
2018 An Adult Patient with Early Pre-B Acute Lymphoblastic Leukemia with t(12;17)(p13;q21)/ZNF384-TAF15. In vivo (Athens, Greece) 8 30150451
2023 NDRG1 promotes endothelial dysfunction and hypoxia-induced pulmonary hypertension by targeting TAF15. Precision clinical medicine 7 37885911
2021 The atypical RNA-binding protein Taf15 regulates dorsoanterior neural development through diverse mechanisms in Xenopus tropicalis. Development (Cambridge, England) 6 34345915
2024 TAF15 inhibits p53 nucleus translocation and promotes HCC cell 5-FU resistance via post-transcriptional regulation of UBE2N. Journal of physiology and biochemistry 5 39446246
2022 The SGYS motif of TAF15 prion-like domain is critical to amyloid fibril formation. Biophysical journal 5 35643629
2018 Genetic activation of parkin rescues TAF15-induced neurotoxicity in a Drosophila model of amyotrophic lateral sclerosis. Neurobiology of aging 5 30339961
2024 Phosphorylation of the compartmentalized PKA substrate TAF15 regulates RNA-protein interactions. Cellular and molecular life sciences : CMLS 4 38568213
2022 circVMA21 combining with TAF15 stabilizes SOCS3 mRNA to relieve septic lung injury through regulating NF-κB activation. Molecular immunology 4 36162226
2022 Reduced oxidative stress suppresses neurotoxicity in the Drosophila model of TAF15-associated proteinopathies. Molecular brain 4 36411469
2022 SR Protein Kinase 1 Inhibition by TAF15. Cells 4 36611919
2009 TAF15 and the leukemia-associated fusion protein TAF15-CIZ/NMP4 are cleaved by caspases-3 and -7. Biochemical and biophysical research communications 4 19426707
2025 Targeting PRMT1-mediated methylation of TAF15 to protect against myocardial infarction by inhibiting ferroptosis via the GPX4/NRF2 pathway. Clinical epigenetics 3 40696470
2024 Promotive actions of lncRNA EBLN3P involved in cervical cancer progression via interacting with miR-29c-3p and TAF15 to modify RCC2. Archives of biochemistry and biophysics 3 38555043
2024 TAF15 downregulation contributes to the benefits of physical training on dendritic spines and working memory in aged mice. Aging cell 3 38874013
2024 RNF144A-AS1 stabilizes TAF15 and promotes malignant biological behaviors of skin cutaneous melanoma. Molecular and cellular biochemistry 3 38878223
2024 circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD. Endocrine journal 2 38811189
2020 SCF-Slimb is critical for Glycogen synthase kinase-3β-mediated suppression of TAF15-induced neurotoxicity in Drosophila. Journal of neurochemistry 2 32915460
2015 Sequence-specific resonance assignments of human TAF15-RRM and TAF15-RRM-RanBP2. Biomolecular NMR assignments 2 24659459
2025 Phase Separation of TAF15 C-Terminal LC Domain Enables RNA-Binding Protein-Mediated Transcriptional Regulation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41085196
2025 TAF15::ZNF384 Mixed Phenotype Acute Leukemia With Complex Karyotype: Case Report With B-ALL Induction, Blinatumomab Bridging to Allogeneic Transplant and Literature Review. Clinical case reports 1 41158816
2024 Knockdown of LncRNA-HAGLR restrains the viability and motility of pancreatic cancer via miR-625-5p/TAF15 axis in vitro and in vivo. Heliyon 1 39309830
2026 The circ_0042103/TAF15/NER axis regulates inflammation and DNA damage in pulpitis. Stem cell research & therapy 0 41530875
2026 Mechanistic study of fibroblast-derived extracellular vesicle miR-25-3p targeting TAF15 to inhibit NF-κB activation and alleviate knee osteoarthritis progression in mice. Joint bone spine 0 41620072
2026 Distinct TAF15 amyloid filament folds define multiple subtypes of FTLD-TAF15. bioRxiv : the preprint server for biology 0 41648099
2026 TAF15 promotes the healing of diabetic foot ulcers by mediating the transcriptional activation of APOE through CEBPB to regulate PTX3. Molecular genetics and genomics : MGG 0 41805994
2026 Molecular Complexities of Dementia: PAISA Mutations and Targeting TAF2N as Therapeutic Avenues. Current gene therapy 0 41820211
2026 Physiological and pathological functions of TAF15 in neurodegenerative diseases and cancers. Journal of advanced research 0 42049092
2026 FUS and TAF15 safeguard the critical functions of the ribonucleoprotein network formed by EWSR1 and newly synthesized RNA. bioRxiv : the preprint server for biology 0 42051291
2026 M6A-modified lncRNA HULC promotes osteosarcoma progression by stabilizing GLUT1 mRNA through interaction with TAF15. Cellular oncology (Dordrecht, Netherlands) 0 42184047
2026 RNA-Binding Protein TAF15 Suppresses Toxicity in a Yeast Model of FUS Proteinopathy. Journal of fungi (Basel, Switzerland) 0 42187823
2025 A guide to selecting high-performing antibodies for TAF15 (UniProt ID: Q92804) for use in western blot, immunoprecipitation, and immunofluorescence. F1000Research 0 40182019
2025 TAF15 mediates ROP16-induced apoptosis and cell cycle arrest in lung cancer. Parasites & vectors 0 40684184
2025 [Clinical features of acute B lymphoblastic leukemia with TAF15::ZNF384 fusion gene]. Zhonghua yi xue za zhi 0 40873094
2025 TAF15 in tumor-associated macrophages enhances protumorigenic polarization and promotes cholangiocarcinoma progression. JHEP reports : innovation in hepatology 0 41244301
2025 The cancer-testis lncRNA LINC01940 promotes gastric cancer malignant progression and chemoresistance by enhancing ribosome biogenesis via TAF15-mediated NOL11 SUMOylation. Cellular & molecular biology letters 0 41402710

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