Affinage

TDRD7

Tudor domain-containing protein 7 · UniProt Q8NHU6

Length
1098 aa
Mass
123.6 kDa
Annotated
2026-04-28
20 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TDRD7 is a Tudor domain- and LOTUS domain-containing RNA-binding scaffold protein that operates in cytoplasmic RNA granules to post-transcriptionally regulate specific mRNA targets, controlling diverse processes including lens fiber cell differentiation, spermatogenesis, autophagy, and innate antiviral defense. In the germline, TDRD7 localizes to nuage/chromatoid bodies in a DDX4/MVH-dependent manner, forms ribonucleoprotein complexes with TDRD1 and TDRD6, orchestrates chromatoid body remodeling, suppresses LINE1 retrotransposons via a pathway distinct from canonical piRNA biogenesis, and drives germ plasm reorganization and chromatin accessibility changes during primordial germ cell fate elaboration (PMID:17141210, PMID:21670278, PMID:33651978). In the lens, TDRD7 directly binds Hspb1 and Tbc1d20 mRNAs through its RNA granule complexes; loss of TDRD7 reduces HSPB1, disrupts the actin cytoskeleton, causes autophagosome accumulation through de-repression of TBC1D20, and results in cataract (PMID:21436445, PMID:32420594, PMID:33618632). TDRD7 also functions as an interferon-stimulated antiviral factor that directly interacts with and inhibits AMPK activation through a discrete AMPK-interacting domain, restricting replication of paramyxoviruses via autophagy suppression and of HSV-1 through an autophagy-independent mechanism (PMID:29381763, PMID:32273341, PMID:37712680).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2006 High

    Establishing that TDRD7 is a nuage/chromatoid body component in the male germline resolved its subcellular compartment and placed it in the Tudor domain protein network: TDRD7 localizes to nuage downstream of DDX4/MVH, forms complexes with TDRD1 and TDRD6, and its repeated Tudor domain architecture is required for germ cell differentiation.

    Evidence Co-IP, co-localization, dominant-negative domain truncations, and Mvh mutant mouse analysis

    PMID:17141210

    Open questions at the time
    • Direct RNA-binding activity of TDRD7 not yet demonstrated
    • Molecular targets and mRNAs regulated by TDRD7 in the germline unknown
    • Relationship to piRNA pathway not established
  2. 2011 High

    Two simultaneous studies revealed TDRD7's dual tissue roles: in the lens, TDRD7 localizes to distinct cytoplasmic RNA granules interacting with STAU1-RNPs and controls lens mRNAs post-transcriptionally, while in the germline, TDRD7 drives chromatoid body remodeling and suppresses LINE1 retrotransposons through a pathway independent of canonical TDRD1/TDRD9-piRNA biogenesis.

    Evidence Tdrd7 knockout mice with lens cataract and spermatogenesis failure; RNA immunoprecipitation; human mutation analysis; genetic epistasis with Tdrd6 double KO

    PMID:21436445 PMID:21670278

    Open questions at the time
    • Specific mRNA targets in the lens identified only by RIP — direct binding not confirmed by orthogonal methods
    • Mechanism of LINE1 suppression independent of piRNA biogenesis not defined
  3. 2012 Medium

    NMR characterization of three LOTUS domains in TDRD7 established that these domains constitute RNA-binding modules, providing a structural basis for TDRD7's function as an RNA-binding protein.

    Evidence NMR resonance assignments (1H, 15N, 13C) of recombinant mouse TDRD7 LOTUS domains

    PMID:22481467

    Open questions at the time
    • Full three-dimensional structures not solved
    • RNA specificity determinants within LOTUS domains not mapped
    • No mutagenesis linking specific LOTUS residues to RNA binding in vivo
  4. 2014 Medium

    Characterization of the Drosophila ortholog Tapas confirmed conserved nuage localization and physical interaction with piRNA pathway components (Aubergine, Argonaute3, Spindle-E, Vasa), and genetic epistasis with its paralog Tejas revealed partially redundant roles in piRNA-mediated transposon silencing.

    Evidence Co-immunoprecipitation pulldowns, single and double mutant analysis in Drosophila

    PMID:25287931

    Open questions at the time
    • Degree of functional conservation between Drosophila Tapas and mammalian TDRD7 not directly tested
    • Direct RNA-binding targets in Drosophila not identified
  5. 2018 High

    An unbiased shRNA screen identified TDRD7 as an interferon-stimulated antiviral factor, revealing a new function: TDRD7 inhibits AMPK activation, thereby suppressing autophagy required for paramyxovirus and RSV replication.

    Evidence High-throughput shRNA screen, knockdown/knockout/overexpression in multiple cell types, AMPK activity assays, chemical AMPK inhibition

    PMID:29381763

    Open questions at the time
    • Mechanism by which TDRD7 inhibits AMPK not determined — direct interaction not yet shown
    • Whether antiviral activity requires TDRD7's RNA-binding or Tudor domains unknown
  6. 2020 High

    Two studies deepened understanding of TDRD7's downstream targets: in the lens, TDRD7-RNP complexes directly bind Hspb1 mRNA to maintain HSPB1 protein levels and F-actin organization; separately, TDRD7 was shown to inhibit AMPK to restrict HSV-1 replication through an autophagy-independent mechanism, establishing that TDRD7's anti-AMPK activity has both autophagy-dependent and autophagy-independent antiviral outputs.

    Evidence RNA immunoprecipitation, single-molecule RNA imaging co-localization, proteomics, Xenopus Hspb1 knockdown; parallel KD/KO/OE and chemical inhibition dissecting autophagy versus AMPK in HSV-1 infection

    PMID:32273341 PMID:32420594

    Open questions at the time
    • How TDRD7 stabilizes or regulates Hspb1 mRNA (translation vs. stability) not resolved
    • Whether the RNA-binding and AMPK-inhibitory functions of TDRD7 are structurally separable not tested
  7. 2021 High

    TDRD7 was shown to promote autophagosome maturation by directly binding and suppressing Tbc1d20 mRNA, linking its RNA-granule function to autophagy regulation: TDRD7 loss de-represses TBC1D20, blocking autophagosome–lysosome fusion and causing autophagosome accumulation in lens and germ cells. In parallel, zebrafish studies demonstrated that Tdrd7 controls germ plasm disaggregation and perinuclear relocalization during PGC migration and drives chromatin accessibility changes for PGC fate elaboration.

    Evidence RIP, autophagic flux assays, TEM, MEF KO analysis; zebrafish tdrd7 mutant with live imaging, ATAC-seq, and transcriptomics

    PMID:33618632 PMID:33651978

    Open questions at the time
    • Whether TDRD7-mediated suppression of Tbc1d20 involves translational repression or mRNA decay is unclear
    • Connection between chromatin accessibility changes and specific TDRD7 molecular activities in PGCs not established
  8. 2023 High

    Domain mapping identified a specific AMPK-interacting region of TDRD7 required for both AMPK inhibition and antiviral activity, and in vivo studies showed that Tdrd7 knockout mice have increased susceptibility to respiratory virus infection, establishing the physiological relevance of TDRD7's antiviral function.

    Evidence Co-immunoprecipitation, domain deletion mutagenesis, primary cell KO analysis, in vivo mouse respiratory infection model

    PMID:37712680

    Open questions at the time
    • Structural basis of the TDRD7–AMPK interaction not resolved
    • Whether AMPK inhibition and RNA-granule/mRNA-regulatory functions of TDRD7 operate through the same or separate domains not fully delineated
    • Whether TDRD7's antiviral activity extends beyond paramyxoviruses and herpesviruses not tested systematically

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for TDRD7's dual RNA-binding and AMPK-inhibitory activities, the full catalog of regulated mRNA targets and the mechanism of their regulation (translational repression vs. mRNA stability), and how TDRD7's germline, lens, and innate immune functions are differentially deployed across cell types.
  • No high-resolution structure of full-length TDRD7 or TDRD7–AMPK complex
  • Genome-wide identification of TDRD7-bound mRNAs by CLIP or equivalent method not performed
  • Mechanism by which TDRD7 influences chromatin accessibility in PGCs is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9612973 Autophagy 3
Partners
DDX4HSPB1PRKAA1STAU1TBC1D20TDRD1TDRD6
Complex memberships
TDRD7-STAU1 RNP granulechromatoid body/nuage RNP

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 TDRD7 is a Tudor domain RNA-binding protein expressed in lens fiber cells that localizes to distinct cytoplasmic RNA granules (TDRD7-RGs) which interact with STAU1-ribonucleoproteins (RNPs). TDRD7 co-immunoprecipitates with specific lens mRNAs and is required for their posttranscriptional control during lens development. Co-immunoprecipitation, loss-of-function (Tdrd7 null mouse), RNA immunoprecipitation, human mutation analysis Science High 21436445
2011 TDRD7 is essential for dynamic remodeling of chromatoid bodies (cytoplasmic RNP assemblies) during spermatogenesis, including their initial establishment, RNP fusion with processing bodies/GW bodies, and structural maintenance. TDRD7 suppresses LINE1 retrotransposons independently of the piRNA biogenesis pathway in which TDRD1 and TDRD9 operate, defining a distinct TDRD pathway against retrotransposons in the male germline. Single and double knockout mouse models (Tdrd7-/-, Tdrd6-/-, double KO), immunofluorescence, co-localization analysis Proceedings of the National Academy of Sciences of the United States of America High 21670278
2006 TDRD7 (TRAP) localizes specifically to nuage/chromatoid bodies in male germ cells and forms a ribonucleoprotein complex together with TDRD1/MTR-1 and TDRD6. Its localization to nuage is downstream of MVH/DDX4, and a single Tudor domain is a structural unit sufficient for nuage localization, while the repeated architecture is functionally essential for germ cell differentiation. Co-localization experiments, Co-IP, in vivo overexpression of truncated dominant-negative forms, Mvh mutant mouse analysis Developmental biology High 17141210
2018 TDRD7 is an interferon-stimulated gene (ISG) that inhibits paramyxovirus (Sendai virus, hPIV3) and RSV replication by inhibiting autophagy. Mechanistically, TDRD7 interferes with the activation of AMP-activated protein kinase (AMPK), which is required for initiating autophagy and for efficient paramyxovirus replication. High-throughput shRNA screen, genetic knockdown/knockout and ectopic expression in multiple cell types, AMPK activity assays, chemical inhibition PLoS pathogens High 29381763
2020 TDRD7 controls the heat shock protein HSPB1 (HSP27) in lens fiber cells by directly binding Hspb1 mRNA via TDRD7-RNP complexes, as demonstrated by RNA immunoprecipitation and single-molecule RNA imaging showing co-localization of TDRD7 protein with cytoplasmic Hspb1 mRNA. Loss of TDRD7 reduces HSPB1 leading to abnormal F-actin cytoskeletal organization and fiber cell morphology defects. RNA immunoprecipitation, single-molecule RNA imaging (co-localization), RNA-seq, 2D-DIGE mass spectrometry, scanning electron microscopy, Xenopus Hspb1 knockdown Human molecular genetics High 32420594
2020 TDRD7 inhibits AMP-activated protein kinase (AMPK) and thereby restricts HSV-1 replication independently of autophagy. AMPK activity is required for HSV-1 replication after viral entry but not through its autophagy function, and TDRD7's antiviral activity depends on its ability to inhibit virus-activated AMPK. Knockdown, knockout, ectopic expression in multiple human and mouse cell types, AMPK activity assays, chemical inhibition of AMPK The Journal of biological chemistry High 32273341
2021 TDRD7 mediates autophagosome maturation by directly binding Tbc1d20 mRNA and downregulating its expression. TBC1D20 is a key regulator of autophagosome maturation; TDRD7 deficiency causes autophagosome accumulation due to failure of autophagosome-lysosome fusion, contributing to cataract and spermiogenesis defects. RNA immunoprecipitation, transcriptome analysis, autophagic flux assays, transmission electron microscopy, MEF knockout analysis Autophagy High 33618632
2023 TDRD7 directly interacts with AMPK to inhibit its activation; a specific AMPK-interacting domain of TDRD7 was identified, and deletion of this domain abolished both anti-AMPK and antiviral activities of TDRD7. TDRD7-deficient primary mouse cells show enhanced AMPK activation and viral replication, and TDRD7 knockout mice exhibit increased susceptibility to respiratory virus infection. Co-immunoprecipitation, domain deletion mutagenesis, primary cell KO analysis, in vivo mouse infection model mBio High 37712680
2021 In zebrafish, Tdrd7 regulates disaggregated perinuclear relocalization of germ plasm during primordial germ cell (PGC) migration and is required for Tdrd7-dependent reconfiguration of chromatin accessibility that drives PGC fate elaboration but not PGC migration per se. Loss-of-function in zebrafish (tdrd7 mutant), live imaging of germ plasm dynamics, ATAC-seq for chromatin accessibility, transcriptome analysis Developmental cell High 33651978
2014 The Drosophila TDRD7 ortholog Tapas (Tap) localizes to perinuclear nuage and physically interacts with piRNA pathway components Aubergine, Argonaute3, Spindle-E, and Vasa. Loss of tap causes mild reduction in germline piRNAs and increased transposon expression; combined loss with its paralog tejas causes more severe piRNA pathway defects and mis-localization of piRNA components. Co-immunoprecipitation (pulldown), genetic epistasis (single and double mutant analysis), immunofluorescence localization BMC biology Medium 25287931
2012 TDRD7 contains three LOTUS (OST-HTH) domains that function as RNA-binding domains; NMR resonance assignments for all three LOTUS domains of mouse TDRD7 were determined, providing the basis for structural characterization of RNA interaction. NMR spectroscopy (1H, 15N, 13C resonance assignments) Biomolecular NMR assignments Medium 22481467
2008 TDRD7 was identified as a scaffold protein found in complexes with proteins that regulate cytoskeleton dynamics, centrosomal movements, mRNA transport, and the protein translation apparatus. Co-immunoprecipitation, immunocytochemistry using validated monoclonal antibodies Hybridoma Low 18582216

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Mutations in the RNA granule component TDRD7 cause cataract and glaucoma. Science (New York, N.Y.) 165 21436445
2011 Tudor domain containing 7 (Tdrd7) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis. Proceedings of the National Academy of Sciences of the United States of America 128 21670278
2006 Tudor-related proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: domain composition, intracellular localization, and function in male germ cells in mice. Developmental biology 127 17141210
2017 Loss-of-function mutations in TDRD7 lead to a rare novel syndrome combining congenital cataract and nonobstructive azoospermia in humans. Genetics in medicine : official journal of the American College of Medical Genetics 84 31048812
2018 A new mechanism of interferon's antiviral action: Induction of autophagy, essential for paramyxovirus replication, is inhibited by the interferon stimulated gene, TDRD7. PLoS pathogens 56 29381763
2014 The Tudor domain protein Tapas, a homolog of the vertebrate Tdrd7, functions in the piRNA pathway to regulate retrotransposons in germline of Drosophila melanogaster. BMC biology 43 25287931
2021 Germ cell differentiation requires Tdrd7-dependent chromatin and transcriptome reprogramming marked by germ plasm relocalization. Developmental cell 33 33651978
2021 TDRD7 participates in lens development and spermiogenesis by mediating autophagosome maturation. Autophagy 29 33618632
2020 The Tudor-domain protein TDRD7, mutated in congenital cataract, controls the heat shock protein HSPB1 (HSP27) and lens fiber cell morphology. Human molecular genetics 28 32420594
2020 The interferon-inducible protein TDRD7 inhibits AMP-activated protein kinase and thereby restricts autophagy-independent virus replication. The Journal of biological chemistry 19 32273341
2021 Genome-Wide Analysis of Differentially Expressed miRNAs and Their Associated Regulatory Networks in Lenses Deficient for the Congenital Cataract-Linked Tudor Domain Containing Protein TDRD7. Frontiers in cell and developmental biology 17 33665188
2015 Gonad specific genes in Atlantic salmon (Salmon salar L.): characterization of tdrd7-2, dazl-2, piwil1 and tdrd1 genes. Gene 17 25668702
2014 RNA granule component TDRD7 gene polymorphisms in a Han Chinese population with age-related cataract. The Journal of international medical research 13 24435515
2019 Comparative studies on duplicated tdrd7 paralogs in teleosts: Molecular evolution caused neo-functionalization. Comparative biochemistry and physiology. Part D, Genomics & proteomics 12 31059868
2021 Recapitulating Evolutionary Divergence in a Single Cis-Regulatory Element Is Sufficient to Cause Expression Changes of the Lens Gene Tdrd7. Molecular biology and evolution 6 32853335
2012 (1)H, (15)N and (13)C resonance assignments for the three LOTUS RNA binding domains of Tudor domain-containing protein TDRD7. Biomolecular NMR assignments 5 22481467
2023 Interferon-stimulated gene TDRD7 interacts with AMPK and inhibits its activation to suppress viral replication and pathogenesis. mBio 4 37712680
2014 Comparative quantification of plasma TDRD7 mRNA in cataract patients by real-time polymerase chain reaction. Korean journal of ophthalmology : KJO 4 25120344
2021 Early germline differentiation in bivalves: TDRD7 as a candidate investigational unit for Ruditapes philippinarum germ granule assembly. Histochemistry and cell biology 1 33770286
2008 Generation and characterization of monoclonal antibodies to TDRD7 protein. Hybridoma (2005) 1 18582216