| 2006 |
TDRD1/MTR-1 localizes to nuage/germinal granules (intermitochondrial cement) in male germ cells, and its intracellular localization is downstream of MVH/DDX4 (mouse vasa homologue). Targeted mutation of Tdrd1 causes male sterility with loss of intermitochondrial cement but retention of chromatoid bodies, establishing TDRD1 as essential for intermitochondrial cement formation downstream of MVH. |
Targeted gene knockout in mice, immunofluorescence localization, analysis of Mvh/Ddx4 mutants |
Proceedings of the National Academy of Sciences of the United States of America |
High |
17038506
|
| 2006 |
TDRD1/MTR-1 forms a ribonucleoprotein complex together with TDRD6 and TDRD7/TRAP at nuage in male germ cells. Their co-localization to nuage is disrupted in Mvh/Ddx4 mutants. Over-expression of truncated single Tudor domain forms acts as dominant negatives detrimental to meiotic spermatocytes, indicating the repeated Tudor domain architecture is functionally essential. |
Co-immunoprecipitation, immunofluorescence co-localization, in vivo over-expression of truncated constructs, analysis in Mvh mutant mice |
Developmental biology |
High |
17141210
|
| 2009 |
TDRD1/MTR-1 physically binds both MILI and MIWI (mouse PIWI proteins) in adult testis. Complex formation among MILI, MIWI, and TDRD1 is critical for their integrated subcellular localization; in MIWI-null round spermatids, MILI and TDRD1 localizations are altered and chromatoid body formation is impaired. |
Co-immunoprecipitation from adult mouse testes, immunofluorescence localization in MIWI-null mutants |
Genes to cells : devoted to molecular & cellular mechanisms |
High |
19735482
|
| 2011 |
Zebrafish Tdrd1 binds both Piwi proteins Ziwi and Zili via sequence-specific interactions between its Tudor domains and symmetrically dimethylated arginines (sDMAs) on Zili. Tdrd1 complexes contain piRNAs and longer RNA molecules (Tdrd1-associated transcripts, TATs) likely representing cleaved Piwi pathway targets and piRNA biogenesis intermediates. Tdrd1 is required for efficient Piwi-pathway activity and proper nuage formation. |
Co-immunoprecipitation, RNA sequencing of Tdrd1 complexes, loss-of-function analysis in zebrafish, biochemical pulldown |
The EMBO journal |
High |
21743441
|
| 2012 |
The four extended Tudor domains (TDs) of murine TDRD1 show differential binding affinity for symmetrically dimethylated arginine (sDMA)-containing peptides from MILI: TD2 and TD3 preferentially bind consecutive MILI peptides, TD4 has lower affinity, and TD1 has very weak affinity but can be restored by a single point mutation restoring the consensus aromatic cage. Crystal structure of TD3 bound to a methylated MILI peptide reveals an unexpected peptide orientation with contacts outside the aromatic cage. SAXS data show the four tandem Tudor domains adopt a flexible, elongated shape. |
Binding affinity measurements (ITC/fluorescence), pulldown with endogenous Piwi proteins, X-ray crystallography of TD3-peptide complex, NMR titration, small-angle X-ray scattering (SAXS), site-directed mutagenesis |
RNA (New York, N.Y.) |
High |
22996915
|
| 2013 |
ERG transcription factor directly activates TDRD1 transcription in prostate cancer by binding a functional ERG binding site in the TDRD1 promoter. ERG governs loss of DNA methylation at the TDRD1 promoter-associated CpG island, and demethylation of the promoter in ERG-negative cancer cells by DNA methyltransferase inhibitors induces TDRD1 expression. |
shRNA knockdown of ERG in VCaP cells, TDRD1 promoter reporter assay, mutation analysis of ERG binding site, MeDIP-Seq, bisulfite sequencing, DNMT inhibitor treatment |
International journal of cancer / PloS one |
Medium |
23319146 23555854
|
| 2023 |
In prostate cancer cells, TDRD1 interacts with multiple subunits of the snRNP biogenesis machinery. In the cytoplasm, TDRD1 binds methylated Sm proteins in a PRMT5-dependent manner; in the nucleus, TDRD1 interacts with Coilin, the scaffold protein of Cajal bodies. Ablation of TDRD1 disrupts Cajal body integrity, impairs snRNP biogenesis, and reduces prostate cancer cell proliferation. |
Mass spectrometry interactome analysis, Co-immunoprecipitation, TDRD1 ablation (knockdown/knockout) with cell proliferation and Cajal body integrity readouts |
Oncogene |
Medium |
37041411
|
| 2024 |
TDRD1 drives intermitochondrial cement (IMC) assembly via liquid-liquid phase separation. Phase separation is driven by cooperation between the tetramerized coiled-coil domain and dimethylarginine-binding Tudor domains, but is independent of the intrinsically disordered region. TDRD1 is recruited to mitochondria by MILI, then sequentially enhances mitochondrial clustering and triggers IMC assembly via phase separation to promote piRNA processing. Mice with TDRD1 phase separation deficiency show disrupted IMC assembly, impaired piRNA biogenesis, transposon de-repression, and spermatogenic arrest. This mechanism is conserved in vertebrates but not in invertebrates. |
Phase separation assays in vitro and in cells, domain mutagenesis (coiled-coil, Tudor domain mutants, IDR deletion), mouse genetic models with phase separation-deficient TDRD1, piRNA sequencing, transposon expression analysis, mitochondrial clustering assays |
Developmental cell |
High |
39029469
|
| 2022 |
TCF7L2 (Wnt pathway transcription factor) binds to and activates the TDRD1 promoter to regulate TDRD1 expression during spermatogonial stem cell (SSC) formation; this binding depends on low DNA methylation at the promoter CpG sites. Overexpression of TDRD1 promotes SSC formation while knockdown has the opposite effect, placing TDRD1 downstream of Wnt/TCF7L2 in SSC biogenesis. |
Dual-luciferase reporter assay, bisulfite sequencing, ChIP, TDRD1 overexpression and knockdown in SSC formation assay (in vitro and in vivo), flow cytometry |
Journal of cellular physiology |
Medium |
35790000
|