| 1997 |
TRAX was identified as a protein partner of Translin via yeast two-hybrid interaction, and found to contain 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 were identified as the protein components of the brain-enriched GS1 single-stranded DNA-binding complex, purified ~500,000-fold and identified by peptide sequencing after UV cross-linking. |
Biochemical purification, UV cross-linking, peptide sequencing |
Journal of neurochemistry |
High |
9681436
|
| 1999 |
TB-RBP (mouse Translin ortholog) forms complexes with Trax, the transitional endoplasmic reticulum ATPase, and cytoskeletal gamma actin in male germ cells; interaction with TER ATPase confirmed by in vitro binding and EM immunocytochemistry; TB-RBP colocalizes with actin in cytoplasm. |
Immunoprecipitation, in vitro binding assay, EM immunocytochemistry, confocal microscopy |
Biochemistry |
Medium |
10471275
|
| 2000 |
Translin and Trax are somatodendritically localized in neurons (Purkinje cells, hippocampal, neocortical pyramidal neurons), enriched in the cytoplasmic fraction relative to nuclear extracts, 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, forms heterodimers with TB-RBP (Translin) under reducing conditions; the Trax-TB-RBP heterodimer inhibits TB-RBP binding to RNA but enhances TB-RBP binding to specific single-stranded DNA sequences; Trax is predominantly cytoplasmic while TB-RBP shuttles between nucleus and cytoplasm using a nuclear export signal. |
In vitro binding assays, yeast two-hybrid, cell fractionation, confocal microscopy, domain mutagenesis |
The Journal of biological chemistry |
High |
11278549
|
| 2002 |
C1D (nuclear matrix protein/DNA-PK activator) interacts specifically with TRAX in a DNA damage-dependent manner; interaction in mammalian cells occurs only following gamma-irradiation; relative expression levels of TRAX and Translin affect their subcellular localization. |
Yeast two-hybrid, co-immunoprecipitation in mammalian cells, fluorescent protein imaging |
Journal of cell science |
Medium |
11801738
|
| 2002 |
Trax is a component of the native Translin/Trax RNA-binding complex in brain; both GS1 (ssDNA) and protamine-2 (RNA) probes label the same heteromeric Translin/Trax complex as demonstrated by Trax antibody supershift and cross-competition. |
Gel-shift assay, antibody supershift, cross-competition, co-transfection in HEK293T cells |
Journal of neurochemistry |
Medium |
12358744
|
| 2003 |
The Translin/Trax heteromeric complex was identified as the glucose response element binding protein (GRBP) in liver that binds the MLTF-like site within the glucose response element of the L-PK gene; the complex exists as large polymers (~240 kDa nuclear, ~420 kDa cytosolic) with a 2:1 Translin:Trax molar ratio. |
Biochemical purification to homogeneity, partial amino acid sequencing, cDNA cloning, gel-shift assay |
Biochimica et biophysica acta |
Medium |
14642810
|
| 2004 |
The subcellular localization of TRAX and TB-RBP (Translin) in male germ cells is determined by their relative expression ratios: increased TRAX:TB-RBP ratio drives nuclear localization; elevated TB-RBP levels retain TRAX in the cytoplasm; this requires direct protein-protein interaction between the two. |
Immunohistochemistry, Western blot, co-expression in COS-1 cells and TB-RBP null MEFs |
The Journal of biological chemistry |
High |
15138261
|
| 2004 |
The Translin/Trax complex recognizes clusters of G residues in RNA rather than the primary sequence of Y and H elements; high affinity binding is preserved after extensive mutation of Y and H elements as long as G clusters are retained. |
Truncation and mutagenesis of protamine-2 3'UTR combined with gel-shift binding assays |
Brain research. Molecular brain research |
Medium |
14741401
|
| 2005 |
Co-expressed recombinant human Translin and Trax form a stable soluble heteromeric complex (~430 kDa, approximately equimolar subunit ratio by MALDI-TOF-MS) that binds both single- and double-stranded DNA; Trax alone aggregates into insoluble complexes. |
Co-expression, MALDI-TOF-MS, gel-shift assay |
FEBS letters |
Medium |
15919079
|
| 2006 |
In Drosophila, translin is essential for stabilizing the Trax protein (translin null mutants show dramatic loss of Trax); conversely, trax is not required for Translin stability; this asymmetric dependency is conserved throughout evolution. |
Translin null mutant generation, trax nonsense mutant isolation, protein level analysis |
Genetics |
High |
17028328
|
| 2007 |
TRAX regulates GAP-43 transcription and axonal regeneration in rat retinal ganglion cells; siRNA-mediated silencing of Trax at P30 results in significant upregulation of GAP-43 transcript and protein and induces axon outgrowth. |
Proteomics identification, siRNA knockdown, transcript and protein analysis |
The European journal of neuroscience |
Medium |
17953615
|
| 2009 |
C3PO, a complex of Translin and Trax, is a Mg2+-dependent endoribonuclease that promotes RISC activation by removing siRNA passenger strand cleavage products; identified using a reconstituted Drosophila long dsRNA- and duplex siRNA-initiated RISC system with recombinant Dicer-2, R2D2, and Ago2. |
In vitro RISC reconstitution with recombinant proteins, biochemical purification, endonuclease assay |
Science |
High |
19661431
|
| 2011 |
Crystal structure of human C3PO reveals an asymmetric octamer barrel consisting of six Translin and two TRAX subunits; this asymmetric assembly is critical for endonuclease function, with cleavage occurring at the interior surface; C3PO activates human Ago2-RISC by degrading the Ago2-nicked passenger strand in a Dicer-independent mechanism. |
Crystal structure determination, in vitro RISC reconstitution with recombinant hAgo2 and C3PO, genetic depletion in mammalian cells |
Nature structural & molecular biology |
High |
21552258
|
| 2011 |
Crystal structure of Drosophila C3PO formed by truncated Translin and Trax reveals hexameric assembly; Trax adopts the translin fold, possesses catalytic centers essential for C3PO endoRNase activity, and interacts extensively with Translin; catalytic pockets of Trax subunits are located within the interior chamber; cleavage leaves 3'-hydroxyl ends; full-length octameric C3PO characterized by EM and mass spectrometry. |
Crystal structure, electron microscopy, mass spectrometry, endoRNase activity assay, mutagenesis of Trax catalytic residues |
Nature structural & molecular biology |
High |
21552261
|
| 2012 |
C3PO (Translin/Trax complex) functions as an RNase that removes 5' pre-tRNA fragments after RNase P processing of pre-tRNAs in Neurospora crassa; this tRNA processing function is conserved in mouse embryonic fibroblast cells; translin and trax mutants have elevated tRNA levels and protein translation. |
Genetic mutant analysis in Neurospora, transcript analysis, mouse embryonic fibroblast cell studies |
Nature structural & molecular biology |
High |
22773104
|
| 2012 |
Both Translin and TRAX contribute to nucleic acid binding in the heteromeric complex; UV laser cross-linking identified TRAX-specific DNA contacts; mutation of the B3 motif in TRAX most severely impaired nucleic acid binding of the heteromeric complex. |
UV-laser cross-linking with radiolabeled ssDNA, site-directed mutagenesis of B2 and B3 motifs |
PloS one |
Medium |
22427937
|
| 2013 |
Crystal structure of Archaeoglobus fulgidus C3PO-like protein reveals an octamer that entirely encapsulates a 13-bp RNA duplex in its inner cavity; Trax-like-subunit catalytic sites target opposite strands separated by 7 base pairs for cleavage, explaining the mechanism of RNA recognition and cleavage. |
Crystal structure of C3PO bound to duplex RNA |
Nature structural & molecular biology |
High |
23353787
|
| 2013 |
PLCβ binds to TRAX (the endonuclease subunit of C3PO) with high affinity; PLCβ binds approximately 5-fold more weakly to Translin than to TRAX, and ~2-fold more strongly to the assembled C3PO octamer; one PLCβ binds per C3PO octamer at an external site without altering TRAX/Translin assembly; PLCβ reduces C3PO hydrolysis rate of siRNA(GAPDH) to match that of the slowly hydrolyzed siRNA(Hsp90), providing mechanistic basis for gene-selective silencing reversal. |
Fluorescence-based binding assays, brightness/stoichiometry measurements, in vitro siRNA hydrolysis assay |
The Journal of biological chemistry |
High |
24338081
|
| 2015 |
TRAX participates in ATM/H2AX-mediated DNA double-strand break repair by interacting with ATM and stabilizing the MRN complex at DSBs; nuclear localization of TRAX (via its NLS) is required for this function; TRAX-null MEFs show impaired ATM and H2AX phosphorylation and increased p53-mediated apoptosis after UV-C or gamma-irradiation. |
Co-immunoprecipitation, TRAX-null MEF rescue with WT vs. NLS-mutant TRAX, phosphorylation assays, irradiation experiments |
Oncogene |
High |
26096928
|
| 2016 |
PLCβ association with TRAX is required for NGF-induced PC12 cell differentiation; PLCβ newly synthesized after NGF treatment associates with TRAX rather than Gαq, impacting RNA-induced silencing to switch cells to differentiated state; TRAX knockdown prevents differentiation. |
FRET, siRNA knockdown, Ca2+ signaling measurements, siRNA reversal assay |
The Journal of biological chemistry |
Medium |
27624933
|
| 2016 |
Crystal structures of Nanoarchaeum equitans C3PO reveal an open apo form with a substrate entryway, and closed forms with ssRNA and ssDNA captured at the inner cavity; the ssRNA complex represents the catalytic form; mutagenesis and in vitro cleavage assays establish a two-cation-assisted catalytic mechanism shared by eukaryotic C3POs. |
Crystal structure determination (apo, ssRNA-bound, ssDNA-bound), mutagenesis, in vitro cleavage assay |
Nucleic acids research |
High |
27596600
|
| 2017 |
Learning triggers the Translin/Trax RNase complex to degrade microRNAs targeting ACVR1C (activin A receptor type 1C); mice lacking translin/trax show increased disease-related microRNAs targeting ACVR1C after learning, loss of synaptic ACVR1C upregulation, and defects in synaptic tagging and long-term memory; ACVR1C inhibition phenocopies these deficits. |
Translin KO mice, microRNA profiling, synaptic tagging electrophysiology, behavioral memory tests, pharmacological ACVR1C inhibition |
eLife |
High |
28927503
|
| 2018 |
GSK3β and DISC1 are novel interacting proteins of TRAX; GSK3β binds TRAX and negatively regulates its ability to facilitate non-homologous end-joining (NHEJ) DNA repair; A2A adenosine receptor stimulation inhibits GSK3β, dissociating the TRAX/DISC1/GSK3β complex and enhancing NHEJ via DNA-PK phosphorylation at Thr2609; pharmacological GSK3β inhibition mimics A2AR effects. |
Co-immunoprecipitation, PC12 cells, primary mouse neurons, iPSC-derived human neurons, DNA repair assays, pharmacological inhibition |
Molecular psychiatry |
High |
29298990
|
| 2018 |
Cryo-EM structures of full-length Drosophila C3PO reveal a closed football-like octamer with a hollow interior; TRAX subunits form dynamic side ports (~25×30 Å) via anti-parallel α1 helices that mediate RNA substrate entry and release; stoichiometry of Drosophila C3PO is TRAX:Translin 4:4. |
Crystal structure (2.1 Å), cryo-EM structures at multiple resolutions, SUMO-tagging for stoichiometry determination |
Nucleic acids research |
High |
29860349
|
| 2019 |
The Translin/Trax RNase complex degrades miR-181b in aortic vascular smooth muscle cells; TN knockout mice show elevated miR-181b in the aorta and are protected from high-salt-induced vascular stiffness; this identifies the TN/TX complex as a physiologically relevant microRNA-degrading enzyme in the vascular system. |
TN KO mice, high-salt water model, pulse wave velocity, tensile testing, microRNA quantification |
American journal of physiology. Heart and circulatory physiology |
High |
31625778
|
| 2020 |
Introduction of the E126A mutation in TRAX (Tsnax) abolishes microRNA-degrading activity of the TN/TX complex without impairing TN or TX protein expression or their co-precipitation; mice homozygous for Tsnax(E126A) display selectively elevated microRNAs and robust adiposity phenotype identical to Tsn KO mice, demonstrating that microRNA-degrading activity drives this metabolic phenotype. |
Knock-in mutagenesis (E126A), co-precipitation, microRNA profiling, body composition analysis, conditional KO in adipocytes and hepatocytes |
Molecular metabolism |
High |
32408014
|
| 2020 |
Translin/Trax mediates a selective form of hippocampal long-term plasticity requiring postsynaptic PKA activity; translin KO mice show impaired NMDAR-dependent LTD but normal presynaptic PKA-dependent plasticity and normal mGluR-LTD, distinguishing the TN/TX pathway from FMRP. |
Translin KO mice, multiple hippocampal LTP/LTD electrophysiology paradigms, pharmacological dissection |
Molecular brain |
Medium |
33172471
|
| 2004 |
Trax co-localizes with Golgi family protein Mea2 in the Golgi complex of mid-late pachytene spermatocytes; this Golgi localization is disrupted by a truncated Mea2 lacking the N-terminal region, suggesting TRAX-Mea2 interaction requires Mea2's N-terminus. |
Immunofluorescent staining, Mea2 mutant mouse analysis |
The journal of histochemistry and cytochemistry |
Low |
15314092
|