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Showing TSNAX — TRAX is a alias.

TSNAX

Translin-associated protein X · UniProt Q99598

Length
290 aa
Mass
33.1 kDa
Annotated
2026-06-10
68 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TSNAX (TRAX) is the catalytic subunit of the heteromeric Translin/TRAX endoribonuclease (C3PO), an asymmetric octamer of six Translin and two TRAX subunits in which the TRAX subunits carry the active sites that cleave RNA within the complex's interior chamber (PMID:21552258, PMID:21552261, PMID:23353787). TRAX cannot bind nucleic acids alone and aggregates insolubly unless co-expressed with Translin, which solubilizes and stabilizes it; the two proteins assemble into a ~430 kDa heteromeric complex that recognizes G-rich RNA and single-stranded DNA, with TRAX contributing directly to binding through its B3 motif (PMID:11278549, PMID:11801738, PMID:14741401, PMID:15919079, PMID:22427937). As a Mg2+-dependent endoribonuclease, C3PO activates RISC by degrading siRNA passenger-strand cleavage products and broadly shapes small-RNA pools by degrading pre-miRNAs and processing 5' pre-tRNA fragments (PMID:19661431, PMID:21552258, PMID:22773104). Active-site mutagenesis (E126) abolishing the miRNA-degrading activity in vivo establishes that this catalytic function underlies physiological roles in adiposity, learning-induced relief of miRNA-mediated translational silencing of ACVR1C at synapses, vascular smooth-muscle stiffening via miR-181b, and neuroprotection in Huntington's disease models (PMID:28927503, PMID:32408014, PMID:34304585, PMID:35997316). The relative TRAX:Translin ratio governs subcellular partitioning—TRAX's nuclear localization signal drives nuclear import while Translin's nuclear export signal retains the complex in the cytoplasm (PMID:11278549, PMID:15138261). Beyond its RNase activity, nuclear TRAX serves as a scaffold for DNA double-strand break repair, interacting with ATM and stabilizing the MRN complex at breaks, and forming a TRAX/DISC1/GSK3β ternary complex that modulates NHEJ-mediated repair downstream of A2A adenosine receptor signaling (PMID:26096928, PMID:29298990).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 Medium

    Established TRAX as a physical partner of Translin and proposed it provides nuclear-targeting capacity that Translin lacks, opening the question of how the pair functions together.

    Evidence Yeast two-hybrid and nuclear-targeting-signal sequence analysis

    PMID:9013868

    Open questions at the time
    • NLS function inferred from sequence, not tested
    • no biochemical activity assigned to TRAX
  2. 1998 High

    Identified Translin and TRAX as the protein components of a brain-enriched single-stranded DNA-binding complex, linking the pair to nucleic acid binding.

    Evidence Biochemical purification, UV cross-linking, peptide sequencing

    PMID:9681436

    Open questions at the time
    • functional consequence of DNA binding unknown
    • no catalytic activity demonstrated
  3. 2001 High

    Defined TRAX as unable to bind nucleic acid alone and as a heterodimer partner that modulates Translin's RNA versus ssDNA binding, and showed differential subcellular distribution of the two proteins.

    Evidence In vitro RNA/DNA binding, fractionation, confocal microscopy, yeast two-hybrid

    PMID:11278549

    Open questions at the time
    • physiological substrate not identified
    • enzymatic role not yet known
  4. 2002 Medium

    Connected TRAX to DNA damage signaling by showing its interaction with C1D occurs only after gamma-irradiation, and established that TRAX:Translin expression ratio controls localization.

    Evidence Yeast two-hybrid, Co-IP in mammalian cells, fluorescence imaging

    PMID:11801738

    Open questions at the time
    • mechanism linking C1D interaction to repair unresolved
    • irradiation-dependence not mechanistically explained
  5. 2004 High

    Mechanistically defined the localization switch: TRAX carries a functional NLS, Translin a functional NES, and their interaction with relative abundance dictates nuclear versus cytoplasmic residence.

    Evidence IHC, overexpression in COS-1, Translin-null MEFs, Western blot

    PMID:14741401 PMID:15138261

    Open questions at the time
    • regulation of the TRAX:Translin ratio in vivo not defined
    • G-cluster RNA recognition not linked to a function
  6. 2005 Medium

    Showed that recombinant Translin solubilizes and stabilizes otherwise-aggregating TRAX into a stable ~430 kDa heteromeric complex, establishing assembly requirements.

    Evidence Recombinant co-expression, MALDI-TOF-MS, DNA-binding/gel-shift

    PMID:15919079

    Open questions at the time
    • precise subunit stoichiometry not yet resolved
    • no enzymatic function assigned
  7. 2006 High

    Genetic nulls in Drosophila established an asymmetric stability dependency—Translin stabilizes TRAX but not vice versa—and found no role for the pair in DSB repair in flies.

    Evidence Drosophila null mutants, Western blot, viability/fertility and DNA-damage assays

    PMID:17028328

    Open questions at the time
    • species-specific divergence in repair role unexplained
    • core molecular function still unidentified at this point
  8. 2009 High

    Defined the core biochemical function: C3PO is a Mg2+-dependent endoribonuclease that activates RISC by degrading siRNA passenger-strand products.

    Evidence In vitro RNAi reconstitution with Dicer-2/R2D2/Ago2, endoribonuclease assay

    PMID:19661431

    Open questions at the time
    • which subunit is catalytic not yet pinpointed
    • endogenous substrates beyond siRNA unknown
  9. 2011 High

    Crystal structures assigned the catalytic centers to TRAX within an asymmetric six-Translin/two-TRAX octamer and confirmed C3PO's requirement for hAgo2-RISC activation in mammalian cells.

    Evidence X-ray crystallography, in vitro RISC reconstitution, siRNA knockdown

    PMID:21552258 PMID:21552261

    Open questions at the time
    • mode of substrate entry into the closed barrel unclear
    • catalytic mechanism details not fully resolved
  10. 2012 High

    Identified endogenous RNA substrates by showing TRAX-containing C3PO removes 5' pre-tRNA fragments after RNase P processing, conserved from Neurospora to mammalian cells, and demonstrated direct TRAX contribution to nucleic acid binding via its B3 motif.

    Evidence Genetic nulls in Neurospora, Northern blot, MEF cells; UV cross-linking with B2/B3 mutagenesis

    PMID:22427937 PMID:22773104

    Open questions at the time
    • physiological role of tRNA fragment processing unclear
    • relative contribution of RNAi vs tRNA roles across tissues undefined
  11. 2013 High

    Structural and biochemical work clarified RNA recognition (duplex encapsulation with strand-spanning catalytic sites) and identified PLCβ as an external regulator that selectively inhibits C3PO cleavage of particular siRNAs.

    Evidence Archaeal C3PO–RNA co-crystal; fluorescence binding and in vitro hydrolysis assays

    PMID:23353787 PMID:24338081

    Open questions at the time
    • PLCβ regulation studied in only one mammalian context
    • duplex-cleavage geometry inferred from archaeal ortholog
  12. 2015 High

    Established a nuclease-independent scaffold role: nuclear TRAX interacts with ATM and stabilizes the MRN complex at DSBs, with NLS-dependent nuclear localization required to rescue repair in TRAX-null cells.

    Evidence Co-IP, TRAX-null MEFs, NLS-mutant rescue, phospho-ATM/H2AX immunoblot, apoptosis assay

    PMID:26096928

    Open questions at the time
    • whether scaffold role requires the octamer or free TRAX unclear
    • species discrepancy with Drosophila repair data unresolved
  13. 2016 High

    Deepened mechanistic understanding with a two-cation catalytic mechanism and open/closed conformational cycle, and extended TRAX function to telomere-associated transcript regulation and PLCβ-dependent PC12 differentiation.

    Evidence N. equitans C3PO structures with mutagenesis/cleavage assay; S. pombe and human transcript analysis; FRET and siRNA in PC12

    PMID:27183912 PMID:27596600 PMID:27624933

    Open questions at the time
    • catalytic details from archaeal ortholog extrapolated to human
    • TERRA regulation mechanism not fully resolved
  14. 2017 High

    Placed C3PO in a learning pathway: the complex relieves miRNA-mediated silencing of ACVR1C at synapses, required for synaptic tagging and long-term memory.

    Evidence Translin KO mice, miRNA profiling, ACVR1C Western blot, synaptic electrophysiology, behavior, pharmacology

    PMID:28927503

    Open questions at the time
    • whether nuclease activity per se drives the synaptic phenotype not isolated here
    • mechanism of activity-dependent regulation unclear
  15. 2018 High

    Refined the structural substrate-entry model (dynamic side ports, 4:4 stoichiometry in full-length Drosophila C3PO) and identified a TRAX/DISC1/GSK3β complex coupling A2A receptor signaling to NHEJ-mediated DNA repair.

    Evidence Crystallography and cryo-EM with SUMO-stoichiometry; Co-IP, NHEJ and phospho-DNA-PK assays across PC12, primary and iPSC neurons

    PMID:29298990 PMID:29860349

    Open questions at the time
    • full-length vs truncated stoichiometry differences across studies
    • how scaffold and nuclease roles are coordinated unclear
  16. 2020 High

    Demonstrated in vivo that the catalytic E126 residue of TRAX is required for the complex's miRNA-degrading activity and for the adiposity phenotype, and that developmental loss—not adult or tissue-restricted loss—drives it.

    Evidence E126A knock-in and conditional KO mice, Co-IP, miRNA profiling, body composition; plus electrophysiology of selective LTP/LTD deficits

    PMID:32408014 PMID:33172471

    Open questions at the time
    • miRNA targets driving adiposity not fully defined
    • developmental window requirement mechanism unexplained
  17. 2022 Medium

    Connected TRAX miRNA-suppressing activity to neuroprotection, with TRAX upregulation in Huntington's disease and its loss accelerating HD-like pathology via a miRNA-mRNA network including DARPP-32 and BDNF.

    Evidence AAV-shRNA TRAX knockdown in HD mice, miRNA-seq, RNA-seq, behavior, IHC, human/mouse striatal cell validation

    PMID:35997316

    Open questions at the time
    • direct miRNA substrates among the 83 not all validated as direct C3PO targets
    • therapeutic relevance untested
  18. 2025 Medium

    Defined pathway specificity through negative results: Tsnax loss in dopaminergic neurons does not affect adiposity or psychostimulant responses, while confirming the asymmetric Translin-dependence of TRAX stability in these cells.

    Evidence DAT-Cre conditional KO, immunostaining, body composition, locomotor and CPP assays

    PMID:40723911

    Open questions at the time
    • cell types responsible for the metabolic and behavioral phenotypes not identified
    • downstream miRNA targets in relevant neurons undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRAX's nuclease activity, DNA-repair scaffolding, and localization switching are coordinated within a single cell, and which endogenous substrates drive each tissue-specific phenotype, remain unresolved.
  • no integrated model linking nuclease and scaffold roles
  • tissue-specific substrate maps incomplete
  • regulation of TRAX:Translin ratio in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 7 GO:0003677 DNA binding 4 GO:0003723 RNA binding 3 GO:0016787 hydrolase activity 2 GO:0060090 molecular adaptor activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 4 GO:0005634 nucleus 3
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-73894 DNA Repair 2
Partners
ATMC1DDISC1GSK3BPLCB1TSN
Complex memberships
C3PO (Translin/TRAX complex)TRAX/DISC1/GSK3β complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 TRAX (Translin-associated factor X) was identified as a protein partner of Translin via yeast two-hybrid assay; TRAX contains bipartite nuclear targeting sequences in its N-terminal region, suggesting a role in selective nuclear transport of Translin, which lacks nuclear targeting motifs. Yeast two-hybrid assay; sequence analysis of nuclear targeting signals FEBS letters Medium 9013868
1998 Translin and TRAX are identified as the protein components of the brain-enriched GS1 single-stranded DNA-binding complex, purified ~500,000-fold by conventional chromatography and affinity column, with both proteins detected by UV cross-linking to the DNA probe. Biochemical purification, affinity chromatography, UV cross-linking, peptide sequencing Journal of neurochemistry High 9681436
1999 TB-RBP (mouse Translin) interacts with TRAX, transitional endoplasmic reticulum ATPase, and cytoskeletal gamma-actin in male germ cells and brain, as demonstrated by immunoprecipitation and in vitro binding assays; TB-RBP co-localizes with actin in the cytoplasm of male germ cells. Immunoprecipitation, in vitro binding assay, confocal microscopy Biochemistry Medium 10471275
2000 Translin and TRAX are both expressed in neurons and are highly enriched in the cytoplasmic fraction compared with nuclear extracts; immunohistochemistry shows Translin (and by implication the Translin/TRAX complex) localizes somatodendritically in Purkinje cells and hippocampal/neocortical pyramidal neurons, supporting a role in dendritic RNA processing. In situ hybridization, subcellular fractionation, immunohistochemistry Journal of neurochemistry Medium 10987859
2001 TRAX does not bind DNA or RNA on its own but forms heterodimers with TB-RBP (Translin) under reducing conditions; the heterodimer inhibits TB-RBP binding to RNA but enhances TB-RBP binding to specific single-stranded DNA sequences. TRAX is predominantly cytoplasmic, whereas TB-RBP uses a nuclear export signal to exit nuclei. In vitro RNA/DNA binding assay, cell fractionation, confocal microscopy, yeast two-hybrid The Journal of biological chemistry High 11278549
2002 The nuclear matrix protein C1D interacts specifically with TRAX in yeast and mammalian cells; however, this interaction in mammalian cells occurs only after gamma-irradiation, linking TRAX to DNA double-strand break repair signaling. Relative expression levels of TRAX and Translin affect their subcellular localization as shown by fluorescent protein imaging. Yeast two-hybrid, co-immunoprecipitation in mammalian cells, fluorescence microscopy with fluorescently tagged proteins Journal of cell science Medium 11801738
2002 Both Translin and TRAX are components of the native RNA-binding gel-shift complex (labeled by either GS1 DNA or protamine-2 RNA probes), as shown by antibody supershift and cross-competition assays; recombinant co-expressed Translin/TRAX heteromers bind both probes, establishing that the native RNA-binding complex is heteromeric. Gel-shift supershift assay, cross-competition assay, co-transfection of recombinant proteins Journal of neurochemistry Medium 12358744
2003 The Translin/TRAX heteromeric complex was identified as the glucose response element binding protein (GRBP) in rat liver, binding to the MLTF-like site within the glucose response element of the liver-type pyruvate kinase gene with high affinity in both cytosolic and nuclear fractions; the cytosolic complex has a molar ratio of Translin:TRAX of 2:1. Biochemical purification to homogeneity, partial amino acid sequencing, cDNA cloning, gel-shift/DNA-binding assay Biochimica et biophysica acta Medium 14642810
2004 The ratio of TRAX to TB-RBP (Translin) determines their subcellular localization: increased TRAX:TB-RBP ratio drives nuclear localization, whereas elevated TB-RBP levels keep TRAX cytoplasmic. TRAX contains a functional nuclear localization signal (NLS) and TB-RBP contains a functional nuclear export signal (NES); their co-localization requires protein-protein interaction between the two. Immunohistochemistry during spermatogenesis, Western blot, overexpression in COS-1 cells, TB-RBP null mouse embryonic fibroblasts The Journal of biological chemistry High 15138261
2004 The Translin/TRAX complex binds RNA with high affinity by recognizing clusters of G residues rather than specific Y or H element primary sequences; extensive mutation of Y and H elements preserves high-affinity binding as long as G-clusters are retained. Gel-shift assay with truncated and mutated RNA oligonucleotides Brain research. Molecular brain research Medium 14741401
2005 Co-expressed recombinant human Translin and TRAX form a stable heteromeric complex of ~430 kDa (estimated octameric/hexameric composition); TRAX expressed alone aggregates insolubly but is solubilized by co-expression with Translin; the complex binds single- and double-stranded DNA. Recombinant co-expression, size determination (MALDI-TOF-MS), DNA binding assay, gel-shift FEBS letters Medium 15919079
2006 In Drosophila, Translin is essential for stabilizing TRAX protein; loss of translin causes dramatic reduction of Trax levels. Conversely, loss of trax does not affect Translin stability. Drosophila translin and trax single/double mutants are viable and fertile, with no detectable role in DNA double-strand break repair, meiotic recombination, or chromosome segregation. Genetic null mutant generation, protein level analysis by Western blot, viability/fertility assays, DNA damage sensitivity assays Genetics High 17028328
2007 TRAX (Trax) regulates GAP-43 expression and axonal regeneration in rat retinal ganglion cells; siRNA-mediated knockdown of Trax during the regeneration window (P16) downregulated both Trax and GAP-43, while knockdown at P30 (post-regeneration) upregulated GAP-43 and induced axonal outgrowth, indicating Trax acts as a molecular switch for GAP-43. siRNA knockdown, quantitative RT-PCR, Western blot, proteomics identification, axon outgrowth assay The European journal of neuroscience Medium 17953615
2009 C3PO (the Translin/TRAX complex) is a Mg2+-dependent endoribonuclease that promotes RISC activation by removing siRNA passenger strand cleavage products; it was purified using a reconstituted RNAi system with Drosophila Dicer-2, R2D2, and Ago2, establishing C3PO as a key activator of the core RNAi machinery. In vitro RNAi reconstitution with recombinant proteins, biochemical purification, endoribonuclease activity assay Science High 19661431
2011 Crystal structure of human C3PO reveals an asymmetric octamer barrel consisting of six Translin and two TRAX subunits; TRAX subunits carry the catalytic centers and cleave RNA at the interior surface. Reconstitution with recombinant human Ago2 and C3PO confirmed C3PO's critical role in hAgo2-RISC activation; genetic depletion of C3PO in mammalian cells compromised RNA silencing. X-ray crystallography, in vitro RISC reconstitution with recombinant hAgo2 and C3PO, siRNA knockdown in mammalian cells Nature structural & molecular biology High 21552258
2011 Crystal structure of hexameric Drosophila C3PO (truncated Translin/TRAX) and EM/MS of octameric full-length C3PO establish that TRAX adopts the translin fold, possesses the catalytic centers essential for C3PO endoRNase activity, interacts extensively with Translin, and that catalytic pockets of TRAX are located within the interior chamber of the octameric scaffold; cleavage leaves 3'-hydroxyl ends and occurs at near-stoichiometric rates. X-ray crystallography, electron microscopy, mass spectrometry, endoRNase activity assay with active-site analysis Nature structural & molecular biology High 21552261
2012 TRAX (within the C3PO complex) functions as an RNase that removes 5' pre-tRNA fragments after processing by RNase P; this tRNA processing role was demonstrated in Neurospora crassa (where C3PO does not significantly contribute to RNAi) and extended to mouse embryonic fibroblast cells, identifying tRNA precursor fragments as endogenous RNA substrates of C3PO. Genetic mutant analysis (translin/trax nulls), Northern blot for tRNA intermediates, complementation assay, mouse embryonic fibroblast cell experiments Nature structural & molecular biology High 22773104
2012 TRAX within the heteromeric Translin/TRAX complex directly contributes to nucleic acid binding; UV laser cross-linking identified both Translin and TRAX as binding to ssDNA; mutagenesis of the B3 motif in TRAX most severely impaired nucleic acid binding activity of the heteromeric complex. UV laser cross-linking with radiolabeled ssDNA, SDS-PAGE identification, site-directed mutagenesis of B2 and B3 motifs PloS one Medium 22427937
2013 Crystal structure of an archaeal C3PO-like octamer (Archaeoglobus fulgidus) in complex with duplex RNA shows the octamer entirely encapsulating a single 13-bp RNA duplex inside its cavity; Trax-like subunit catalytic sites target opposite strands of the duplex for cleavage separated by 7 base pairs, providing mechanistic insight into RNA recognition and cleavage. X-ray crystallography of archaeal C3PO–RNA co-crystal Nature structural & molecular biology High 23353787
2013 PLCβ binds ~5-fold more weakly to Translin than to TRAX and ~2-fold more strongly to the intact C3PO octamer; one PLCβ binds per C3PO octamer at an external site without altering TRAX/Translin assembly; PLCβ inhibits C3PO hydrolysis of siRNA(GAPDH) (which C3PO cleaves faster) to a rate comparable to siRNA(Hsp90), explaining selective gene silencing reversal. Fluorescence-based binding assays, in vitro RNA hydrolysis assay, brightness studies, microarray analysis in PLCβ1-overexpressing cells The Journal of biological chemistry Medium 24338081
2015 TRAX participates in ATM/H2AX-mediated DNA repair by interacting with ATM and stabilizing the MRN complex at double-strand breaks; TRAX nuclear localization (via its NLS) is required for this function, as a NLS-lacking variant fails to rescue DNA repair deficiency in TRAX-null MEFs; TRAX-null MEFs show reduced ATM and H2AX phosphorylation after UV-C or gamma-irradiation and higher p53-mediated apoptosis. Co-immunoprecipitation (TRAX with ATM and MRN complex), TRAX-null MEFs, rescue with WT vs NLS-mutant TRAX, phospho-ATM/H2AX immunoblotting, apoptosis assay Oncogene High 26096928
2016 Crystal structures of Nanoarchaeum equitans C3PO in apo, ssRNA-bound, and ssDNA-bound forms reveal: the apo form adopts an open conformation with a substrate entry way; RNA/DNA complexes form a closed football shape; the ssRNA-bound structure identifies a two-cation-assisted catalytic mechanism; mutagenesis and in vitro cleavage assays confirm catalytic residues, establishing mechanistic details shared by eukaryotic C3POs. X-ray crystallography (three structures), site-directed mutagenesis, in vitro RNA cleavage assay Nucleic acids research High 27596600
2016 PLCβ association with TRAX (rather than with Gαq) is required for PC12 cell differentiation by nerve growth factor; newly synthesized PLCβ binds TRAX and impacts RNA-induced silencing; downregulation of either PLCβ1 or TRAX prevents differentiation, whereas downregulation of Gαq at constant PLCβ does not affect differentiation. FRET, siRNA knockdown of PLCβ1/TRAX/Gαq, Ca2+ signaling assay, siRNA-reversal assay, Western blot during differentiation time course The Journal of biological chemistry Medium 27624933
2016 Translin and TRAX have reciprocal and opposing effects on telomere-associated transcript regulation in fission yeast: mutation of tfx1+ (Trax) elevates sub-telomeric transcripts, whereas Tsn1 (Translin) represses TERRA levels; for some sub-telomeric transcripts, Trax effects depend on Translin. Human Translin and Trax also control telomere-associated transcript levels in human cells. Transcript analysis in S. pombe tfx1 and tsn1 mutants, human cell experiments Oncotarget Medium 27183912
2017 Translin/trax complex is required for learning-induced relief of microRNA-mediated translational silencing; mice lacking translin/trax show increased hippocampal microRNAs targeting ACVR1C after learning, fail to upregulate ACVR1C protein at synapses, and display deficits in synaptic tagging and long-term memory that are phenocopied by ACVR1C inhibition. Translin KO mice, microRNA profiling, Western blot for ACVR1C, synaptic tagging electrophysiology, behavioral memory assays, pharmacological ACVR1C inhibition eLife High 28927503
2018 GSK3β and DISC1 are novel interacting proteins of TRAX; TRAX/DISC1/GSK3β form a ternary complex. A2A adenosine receptor (A2AR) stimulation inhibits GSK3β, dissociates the TRAX/DISC1/GSK3β complex, and facilitates NHEJ-mediated DNA repair by enhancing DNA-PK activation (phospho-Thr2609). GSK3β negatively regulates TRAX's ability to promote NHEJ repair; pharmacological GSK3β inhibition also releases TRAX for oxidative DNA damage repair. Co-immunoprecipitation (TRAX with GSK3β and DISC1), phospho-DNA-PK assay, NHEJ assay, PC12 cells, primary mouse neurons, iPSC-derived human neurons, pharmacological inhibitors Molecular psychiatry High 29298990
2018 Crystal and cryo-EM structures of full-length Drosophila C3PO reveal a 'Dynamic Side Port' model: the apo mutant (E126Q) adopts a half-barrel in crystal but a closed football in cryo-EM; TRAX α1 helices form wide dynamic side ports (~25×30 Å) for RNA substrate entry and release; SUMO-C3PO stoichiometry confirms TRAX:Translin is 4:4 in full-length Drosophila C3PO. X-ray crystallography (E126Q mutant), cryo-EM (three structures), stoichiometry analysis via SUMO-tagging Nucleic acids research High 29860349
2019 The translin/trax (TN/TX) complex degrades miR-181b in vascular smooth muscle cells (VSMCs); deletion of TN in mice elevates aortic miR-181b levels and prevents high-salt-induced vascular stiffening as assessed by pulse wave velocity and tensile testing. TN knockout mice, high-salt hypertension model, miRNA quantification, pulse wave velocity, tensile testing American journal of physiology. Heart and circulatory physiology Medium 31625778
2019 Drosophila C3PO (dmC3PO) promotes accumulation of esi-2.1 siRNA passenger strand and loss of dmC3PO de-represses the endogenous slicer target mus308; loss of dmC3PO also increases miR-bantam abundance, indicating dmC3PO regulates both endogenous siRNA and miRNA pathways. dmC3PO loss-of-function (depletion), small RNA quantification, target gene de-repression assay Acta biochimica et biophysica Sinica Low 30576408
2020 Introduction of the E126A mutation in TRAX (Tsnax) abolishes the microRNA-degrading activity of the TN/TX complex (without affecting TN or TX protein levels or their co-precipitation) and phenocopies the robust adiposity of Tsn knockout mice; selective deletion of Tsn or Tsnax from adipocytes or hepatocytes does not recapitulate the adiposity, and global conditional deletion in adulthood is also insufficient, indicating developmental inactivation of the TN/TX microRNA-degrading enzyme is required. Active-site mutagenesis (E126A knock-in), conditional KO mice (adipocyte-specific, hepatocyte-specific), co-immunoprecipitation, miRNA profiling, body composition analysis Molecular metabolism High 32408014
2020 Translin/trax is selectively required for postsynaptic PKA-dependent persistent hippocampal LTP and NMDAR-dependent LTD, but not for presynaptic PKA-dependent plasticity or mGluR-LTD; translin KO mice exhibit selective plasticity deficits distinct from those of FMRP KO mice. Translin KO mice, hippocampal slice electrophysiology (LTP, LTD with pharmacological dissection of PKA pathways), behavioral memory assays Molecular brain Medium 33172471
2021 The translin/trax RNase complex degrades premature miR-181b (pre-miR-181b), increasing VSMC stiffness; this represents a mechanistic link between C3PO's pre-miRNA degrading activity and vascular function. Translin/trax complex activity assay on pre-miRNA substrate, VSMC stiffness measurements Hypertension Low 34304585
2022 TRAX is upregulated in HD patient and mouse model brains; TRAX downregulation enhances 83 microRNAs (including miR-330-3p and miR-496a-3p) and alters corresponding mRNA networks including DARPP-32 and BDNF; disruption of this TRAX-mediated miRNA-mRNA axis accelerates HD-like symptoms (motor deficits, mHTT aggregates, shortened neurite outgrowth), indicating TRAX provides neuroprotection by suppressing a subset of microRNAs. AAV-shRNA knockdown of TRAX in HD mice, miRNA-sequencing, RNA-sequencing, behavioral assays, immunohistochemistry, biochemical validation in mouse and human striatal cells Movement disorders Medium 35997316
2025 Conditional knockout of Tsnax (TX/TRAX) in dopaminergic neurons (using DAT-Cre) does not affect adiposity, locomotor responses to cocaine or amphetamine, or amphetamine conditioned place preference; Tsn deletion abolished TX protein expression in DA neurons (asymmetric dependency), while Tsnax deletion did not affect TN levels in these cells. Conditional KO mice (DAT-Cre), immunostaining, body composition analysis, locomotor assays, conditioned place preference Biomolecules Medium 40723911

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of general psychiatry 263 16275808
2009 C3PO, an endoribonuclease that promotes RNAi by facilitating RISC activation. Science (New York, N.Y.) 188 19661431
2011 Structure of C3PO and mechanism of human RISC activation. Nature structural & molecular biology 117 21552258
2000 Chromosomal location and genomic structure of the human translin-associated factor X gene (TRAX; TSNAX) revealed by intergenic splicing to DISC1, a gene disrupted by a translocation segregating with schizophrenia. Genomics 89 10945471
1997 Isolation and characterization of a cDNA encoding a Translin-like protein, TRAX. FEBS letters 89 9013868
2011 Multimeric assembly and biochemical characterization of the Trax-translin endonuclease complex. Nature structural & molecular biology 58 21552261
2009 Association of DISC1 and TSNAX genes and affective disorders in the depression case-control (DeCC) and bipolar affective case-control (BACCS) studies. Molecular psychiatry 56 19255581
2000 Somatodendritic localization of Translin, a component of the Translin/Trax RNA binding complex. Journal of neurochemistry 55 10987859
2001 Trax (translin-associated factor X), a primarily cytoplasmic protein, inhibits the binding of TB-RBP (translin) to RNA. The Journal of biological chemistry 52 11278549
2002 DNA damage-dependent interaction of the nuclear matrix protein C1D with Translin-associated factor X (TRAX). Journal of cell science 49 11801738
2009 A 1q42 deletion involving DISC1, DISC2, and TSNAX in an autism spectrum disorder. American journal of medical genetics. Part A 47 19606485
1996 Evaluation of the FACScount, TRAx CD4 and Dynabeads methods for CD4 lymphocyte determination. Journal of immunological methods 46 8814325
1999 Protein-protein interactions between the testis brain RNA-binding protein and the transitional endoplasmic reticulum ATPase, a cytoskeletal gamma actin and Trax in male germ cells and the brain. Biochemistry 45 10471275
2005 Association study of the DISC1/TRAX locus with schizophrenia in a Japanese population. Schizophrenia research 40 16039834
2004 The relative levels of translin-associated factor X (TRAX) and testis brain RNA-binding protein determine their nucleocytoplasmic distribution in male germ cells. The Journal of biological chemistry 40 15138261
1993 The Escherichia coli K-12 F plasmid gene traX is required for acetylation of F pilin. Journal of bacteriology 39 8444800
2008 The Translin/Trax RNA binding complex: clues to function in the nervous system. Biochimica et biophysica acta 38 18424275
2014 Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing. Carcinogenesis 37 25239642
2018 GSK3β negatively regulates TRAX, a scaffold protein implicated in mental disorders, for NHEJ-mediated DNA repair in neurons. Molecular psychiatry 32 29298990
1998 Identification of translin and trax as components of the GS1 strand-specific DNA binding complex enriched in brain. Journal of neurochemistry 30 9681436
2017 Learning induces the translin/trax RNase complex to express activin receptors for persistent memory. eLife 29 28927503
2006 Functional characterization of Drosophila Translin and Trax. Genetics 28 17028328
2012 The translin-TRAX complex (C3PO) is a ribonuclease in tRNA processing. Nature structural & molecular biology 25 22773104
2002 Trax is a component of the Translin-containing RNA binding complex. Journal of neurochemistry 25 12358744
1995 Comparison of CD4 cell count by a simple enzyme-linked immunosorbent assay using the TRAx CD4 test kit and by flow cytometry and hematology. Clinical and diagnostic laboratory immunology 25 7719901
2018 The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions. Journal of biomedical science 23 30285728
2005 Cloning and characterization of the Schizosaccharomyces pombe homologs of the human protein Translin and the Translin-associated protein TRAX. Nucleic acids research 23 16043634
2015 A central role of TRAX in the ATM-mediated DNA repair. Oncogene 22 26096928
2013 Catalytic domain of plasmid pAD1 relaxase TraX defines a group of relaxases related to restriction endonucleases. Proceedings of the National Academy of Sciences of the United States of America 22 23904483
2007 Functional characterisation of the Schizosaccharomyces pombe homologue of the leukaemia-associated translocation breakpoint binding protein translin and its binding partner, TRAX. Biochimica et biophysica acta 20 18062930
1995 Characterization of traX, the F plasmid locus required for acetylation of F-pilin subunits. Journal of bacteriology 20 7768788
2007 Translin-associated factor-X (Trax) is a molecular switch of growth-associated protein (GAP)-43 that controls axonal regeneration. The European journal of neuroscience 19 17953615
2016 Phospholipase Cβ-TRAX Association Is Required for PC12 Cell Differentiation. The Journal of biological chemistry 18 27624933
2005 Co-expressed recombinant human Translin-Trax complex binds DNA. FEBS letters 18 15919079
2012 Identification of nucleic acid binding sites on translin-associated factor X (TRAX) protein. PloS one 17 22427937
2014 DISC1-TSNAX and DAOA genes in major depression and citalopram efficacy. Journal of affective disorders 16 25043320
2019 Deletion of the microRNA-degrading nuclease, translin/trax, prevents pathogenic vascular stiffness. American journal of physiology. Heart and circulatory physiology 15 31625778
2013 Structural basis for duplex RNA recognition and cleavage by Archaeoglobus fulgidus C3PO. Nature structural & molecular biology 15 23353787
2013 Hydrolysis rates of different small interfering RNAs (siRNAs) by the RNA silencing promoter complex, C3PO, determines their regulation by phospholipase Cβ. The Journal of biological chemistry 15 24338081
2009 Translin-associated factor X gene (TSNAX) may be associated with female major depressive disorder in the Japanese population. Neuromolecular medicine 15 19760522
2017 Multiple Pathways Mediate MicroRNA Degradation: Focus on the Translin/Trax RNase Complex. Advances in pharmacology (San Diego, Calif.) 13 29413516
2020 Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity. Molecular brain 12 33172471
2004 High affinity binding of the Translin/Trax complex to RNA does not require the presence of Y or H elements. Brain research. Molecular brain research 12 14741401
2018 Trax: A versatile signaling protein plays key roles in synaptic plasticity and DNA repair. Neurobiology of learning and memory 10 30017897
2020 Genetic inactivation of the translin/trax microRNA-degrading enzyme phenocopies the robust adiposity induced by Translin (Tsn) deletion. Molecular metabolism 9 32408014
2017 Regulation of the activity of the promoter of RNA-induced silencing, C3PO. Protein science : a publication of the Protein Society 9 28714243
2016 Translin and Trax differentially regulate telomere-associated transcript homeostasis. Oncotarget 9 27183912
2016 Structural basis for single-stranded RNA recognition and cleavage by C3PO. Nucleic acids research 9 27596600
2001 Masking of the Translin/Trax complex by endogenous RNA. FEBS letters 9 11389888
2010 Analysis of nucleic acid binding by a recombinant translin-trax complex. Biochemical and biophysical research communications 8 20450889
2021 Degradation of Premature-miR-181b by the Translin/Trax RNase Increases Vascular Smooth Muscle Cell Stiffness. Hypertension (Dallas, Tex. : 1979) 7 34304585
1996 Comparison of absolute CD4+ lymphocyte counts determined by enzyme immunoassay (TRAx CD4 test kit) and flow cytometry. Clinical and diagnostic laboratory immunology 7 8807198
2020 Translin-Trax: Considerations for Oncological Therapeutic Targeting. Trends in cancer 6 32460000
2018 Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins. Annals of the New York Academy of Sciences 6 29740830
2003 Identification of Translin/Trax complex as a glucose response element binding protein in liver. Biochimica et biophysica acta 6 14642810
1997 Helper T-lymphocyte count. TRAx CD4 test kit versus conventional flow cytometry. Archives of pathology & laboratory medicine 6 9302928
2004 Co-localization of Trax and Mea2 in Golgi complex of pachytene spermatocytes in the mouse. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 5 15314092
2000 Genomic structure and chromosomal localization of the gene encoding TRAX, a Translin-associated factor X. Journal of human genetics 4 11043515
2025 Analyzing, visualizing, and annotating tRNA-derived RNAs using tRAX and tDRnamer. Methods in enzymology 3 39952700
2019 Opposite effects of Drosophila C3PO on gene silencing mediated by esi-2.1 and miRNA-bantam. Acta biochimica et biophysica Sinica 3 30576408
2018 Structural insights into Drosophila-C3PO complex assembly and 'Dynamic Side Port' model in substrate entry and release. Nucleic acids research 3 29860349
2011 Lack of association between translin-associated factor X gene (TSNAX) and methamphetamine dependence in the Japanese population. Progress in neuro-psychopharmacology & biological psychiatry 3 21683752
2023 The associations between cognitive functions and TSNAX genetic variations in patients with schizophrenia. Pharmacology, biochemistry, and behavior 2 37030547
2022 TRAX Provides Neuroprotection for Huntington's Disease Via Modulating a Novel Subset of MicroRNAs. Movement disorders : official journal of the Movement Disorder Society 2 35997316
2025 Viral and Immune Factors Associated With COVID-19 Outcome in the C3PO Trial of Convalescent Plasma. The Journal of infectious diseases 1 40037339
2025 RNAi Regulator C3PO Promotes Arbovirus Infection in Insect Vectors. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41173802
2025 Conditional Deletion of Translin/Trax in Dopaminergic Neurons Reveals No Impact on Psychostimulant Behaviors or Adiposity. Biomolecules 0 40723911
2014 [Association study of LIS1 and TSNAX genes with bipolar disorder in Chinese Han population]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 24928020

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