Affinage

TERF1

Telomeric repeat-binding factor 1 · UniProt P54274

Length
439 aa
Mass
50.2 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TERF1 (TRF1) is a homodimeric, Myb-domain telomeric repeat-binding protein that functions as a central scaffold at chromosome ends, coordinating telomere length homeostasis, telomere replication, R-loop suppression, and chromosome segregation. TRF1 binds duplex TTAGGG repeats and bends the DNA ~120°, nucleating shelterin assembly by bridging TRF2 through TIN2; it negatively regulates telomere length by gating XPF nuclease access and suppresses TRF2-induced TERRA R-loop invasion through its N-terminal acidic domain, while also repressing homologous recombination and POLD3-dependent break-induced replication at telomeres (PMID:9130722, PMID:15316005, PMID:19124610, PMID:29358759, PMID:31934863). TRF1 telomere occupancy peaks in mitosis, driven by Plk1/Cdk1 phosphorylation at Ser-435 and stabilization by GNL3L and PinX1, and during S-phase its dynamic association is modulated by PARP1-mediated PARylation that recruits WRN/BLM helicases to resolve replication stress (PMID:18625707, PMID:16424898, PMID:19487455, PMID:36864251). Beyond telomeres, TRF1 has a telomere-independent role in mitotic fidelity: it is required for centromeric Aurora-B recruitment and proper sister-centromere cohesion, and interacts with the meiotic adaptor TERB1 via its TRFH domain, whose disruption causes male infertility with meiotic arrest (PMID:24752893, PMID:29083416).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Establishing how TRF1 recognizes telomeric DNA resolved a foundational question: TRF1 homodimerizes through its N-terminal domain, requires both Myb repeats for stable binding, and bends telomeric DNA ~120°, explaining how a single protein can organize higher-order telomeric structure.

    Evidence Yeast two-hybrid, gel-shift, and DNA-bending assays with recombinant TRF1 and deletion mutants

    PMID:9130722

    Open questions at the time
    • No structural resolution at atomic level for full-length dimer
    • Bending angle measured on linear substrates only; relevance to t-loop topology not tested
  2. 2001 High

    Identifying PinX1 as a direct TRF1-binding partner that simultaneously inhibits telomerase via its TID domain linked TRF1's telomere-capping function to active telomere-length regulation through telomerase control.

    Evidence Co-immunoprecipitation, in vitro binding, telomerase activity assays, and overexpression/knockdown in human cells

    PMID:11701125

    Open questions at the time
    • Whether PinX1 inhibits telomerase in a TRF1-dependent manner in vivo was not resolved
    • Structural basis of the trimeric TRF1–PinX1–hTERT complex unclear
  3. 2003 High

    Conditional TRF1 deletion in mouse ES cells showed it is essential for genomic stability and shelterin integrity: loss caused chromosomal fusions with retained telomeric DNA, displaced TIN2 and TRF2, but did not immediately shorten telomeres, separating TRF1's capping role from length regulation.

    Evidence Conditional knockout in mouse ES cells with telomere FISH, immunofluorescence, and chromosomal analysis

    PMID:14559908

    Open questions at the time
    • Whether fusions reflect deprotection or replication failure was unclear
    • In vivo organismal consequences not yet tested
  4. 2004 High

    Discovery that TIN2 simultaneously bridges TRF1 and TRF2 established TRF1 as an architectural pillar of the shelterin complex, explaining how TRF1 loss destabilizes TRF2 and hRap1 at telomeres.

    Evidence Mass spectrometry, Far-Western, yeast two-hybrid, and siRNA knockdown with immunofluorescence

    PMID:15316005

    Open questions at the time
    • Stoichiometry and dynamics of the TRF1–TIN2–TRF2 ternary complex not resolved
  5. 2004 High

    Demonstrating that telomere-bound TRF1 stalls replication forks in vitro and in cells revealed that TRF1 is not merely a cap but an active impediment to the replication machinery, raising the question of how cells resolve this barrier.

    Evidence SV40 replication assay in vitro with recombinant TRF1, flow cytometry and replication-focus analysis in HeLa cells

    PMID:15007108

    Open questions at the time
    • Mechanism by which replication fork stalling is overcome (helicase recruitment) not identified at this stage
  6. 2006 High

    Two advances established cell-cycle regulation of TRF1 telomere association: Xenopus TRF1 binds telomeric chromatin specifically in mitosis under Polo-like kinase control, and TRF1 can access telomeric sites within nucleosomes, forming stable ternary complexes.

    Evidence Xenopus egg extract fractionation with Plx1 immunodepletion and kinase assays; in vitro reconstitution of TRF1–nucleosome–DNA complexes

    PMID:16424898 PMID:16756990

    Open questions at the time
    • Whether nucleosomal binding is regulated by phosphorylation was untested
    • Plx1/Plk1 phosphorylation site on TRF1 not yet mapped
  7. 2008 High

    Mapping Plk1 phosphorylation of TRF1 to Ser-435 (primed by Cdk1) and showing it dramatically increases DNA binding during mitosis provided the molecular mechanism for cell-cycle-dependent telomere association first observed in Xenopus.

    Evidence In vitro/in vivo kinase assays, phospho-site mutagenesis, cell-cycle-staged DNA binding assays

    PMID:18625707

    Open questions at the time
    • Whether Ser-435 phosphorylation also affects TIN2 bridging or shelterin architecture unknown
  8. 2009 High

    Two studies clarified TRF1 stability control and telomere-length regulation: GNL3L stabilizes TRF1 by blocking FBX4-mediated ubiquitylation and is required for mitotic TRF1 accumulation, while transgenic TRF1 overexpression shortens telomeres through XPF nuclease, identifying the downstream effector of TRF1-dependent length control.

    Evidence Co-IP, ubiquitylation assays, cell-cycle analysis for GNL3L; transgenic mice with XPF genetic rescue for length regulation

    PMID:19124610 PMID:19487455

    Open questions at the time
    • How TRF1 recruits or licenses XPF at telomeres remains mechanistically unresolved
    • Whether GNL3L regulation is conserved in humans not shown
  9. 2012 Medium

    PinX1 was shown to stabilize TRF1 on telomeres specifically during mitosis and to prevent its ubiquitylation-dependent degradation, converging with GNL3L as a second TRF1 stabilizer and revealing that TRF1 turnover is a key regulatory node.

    Evidence Cell-cycle fractionation, siRNA knockdown, ubiquitylation assays, co-IP

    PMID:22331467 PMID:24415760

    Open questions at the time
    • Single-lab findings; epistatic relationship between PinX1 and GNL3L not tested
    • Complex hTERT-dependent effects on TRF1 stability not fully resolved
  10. 2014 High

    TRF1 was discovered to have a telomere-independent mitotic function: its depletion abolished centromeric Aurora-B recruitment and loosened sister-centromere cohesion, causing merotelic attachments and aneuploidy—rescued by a telomere-binding-deficient TRF1 mutant.

    Evidence siRNA knockdown, immunofluorescence for Aurora-B, chromosome segregation analysis, rescue with DNA-binding mutant

    PMID:24752893

    Open questions at the time
    • How TRF1 reaches centromeres and directly promotes Aurora-B recruitment is unknown
    • Whether this role requires dimerization or post-translational modifications untested
  11. 2017 High

    Multiple regulatory inputs to TRF1 were resolved: Nek7 phosphorylation at Ser-114 protects TRF1 from FBX4-mediated degradation after oxidative damage; TNKS1 PARylates TRF1 to recruit SSBR factors; AURKB phosphorylates TRF1 at Ser-404 to promote telomere binding; and TERB1 binds TRF1's TRFH domain during meiosis, with disruption causing male infertility.

    Evidence In vitro kinase/PARylation assays, phospho-site mutagenesis, crystal structure of TRFH–TERB1, knock-in mice with meiotic analysis

    PMID:28160604 PMID:28216227 PMID:29040668 PMID:29083416

    Open questions at the time
    • Integration of multiple simultaneous phosphorylation events on a single TRF1 molecule not addressed
    • Whether Nek7, AURKB, and Plk1 modifications are mutually exclusive or cooperative is unknown
  12. 2018 High

    The discovery that TRF1's N-terminal acidic domain suppresses TRF2-induced TERRA R-loop invasion at telomeres revealed a previously unknown antagonistic interplay between the two shelterin DNA-binding subunits in controlling telomeric RNA–DNA hybrids.

    Evidence In vitro RNA invasion assays with domain mutants, in vivo TRF1 depletion with R-loop detection and telomere-loss measurement

    PMID:29358759

    Open questions at the time
    • How the acidic domain biochemically inhibits strand invasion is not structurally resolved
    • Whether R-loop suppression is coupled to replication remains untested
  13. 2020 High

    Proteomic analysis of TRF1-depleted telomeres showed wholesale telomere composition reorganization, with recruitment of HR and BIR machineries; TRF1 suppresses TERRA transcription, HR, and POLD3-dependent BIR, defining it as a master suppressor of illegitimate recombination at telomeres.

    Evidence Mass spectrometry of telomere proteome, HR/BIR assays, TERRA quantification, conditional TRF1 deletion in mouse cells

    PMID:31934863

    Open questions at the time
    • Whether recombination suppression is direct or secondary to R-loop accumulation is unresolved
  14. 2023 High

    PARP1-mediated PARylation of TRF1 during S-phase was shown to modulate TRF1's dynamic telomere association and enable recruitment of WRN and BLM helicases for replication-fork resolution, finally explaining how cells overcome the replication barrier posed by TRF1-bound telomeres.

    Evidence PARylation assays, PARP1 inhibition/KO, telomere BrdU incorporation, co-IP for helicase recruitment, telomere fragility assessment

    PMID:36864251

    Open questions at the time
    • Whether PARP1 modifies specific TRF1 residues or domains is not mapped
    • Interplay between PARP1 and TNKS1 PARylation of TRF1 at replication forks vs. damage sites not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include how TRF1 is recruited to centromeres for its telomere-independent mitotic role, how multiple simultaneous post-translational modifications (Plk1, Cdk1, Nek7, AURKB phosphorylations; PARP1 and TNKS1 PARylation; FBX4 ubiquitylation) are coordinated on a single TRF1 dimer in real time, and what structural mechanism underlies acidic-domain-mediated R-loop suppression.
  • No structural model of full-length TRF1 dimer with post-translational modifications
  • Centromeric recruitment mechanism completely undefined
  • In vivo single-molecule dynamics of TRF1 modification states unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0000228 nuclear chromosome 6 GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 2 R-HSA-1474165 Reproduction 1
Partners
GNL3LMAPRE1PARP1PINX1TERB1TERF2TINF2TNKS
Complex memberships
Shelterin

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 TRF1 binds telomeric DNA as a homodimer, using a conserved N-terminal domain for TRF1-TRF1 dimerization, and requires both Myb repeats for stable DNA complex formation; TRF1 bends its telomeric DNA binding site to an angle of approximately -120 degrees. Yeast two-hybrid, gel shift/DNA binding assays, biochemical dimerization analysis, DNA bending assays The EMBO journal High 9130722
2001 PinX1 binds TRF1 (Pin2) directly and also binds the telomerase catalytic subunit hTERT through its TID domain, potently inhibiting telomerase activity; PinX1 overexpression shortens telomeres and induces crisis, while depletion increases telomerase activity and elongates telomeres. Co-immunoprecipitation, in vitro binding assays, overexpression and siRNA knockdown with telomere length and telomerase activity assays Cell High 11701125
2004 TIN2 directly binds both TRF1 and TRF2 simultaneously, linking the two telomeric complexes; TIN2 depletion reduces TRF2 and hRap1 at telomeres, demonstrating that TIN2 stabilizes TRF2 on telomeres through cooperative bridging. Mass spectrometry, co-immunoprecipitation, Far-Western assays, yeast two-hybrid, siRNA knockdown with chromatin immunofluorescence The Journal of biological chemistry High 15316005
2005 A single 8-oxo-guanine lesion in telomeric DNA reduces TRF1 binding by at least 50%; multiple 8-oxo-guanine lesions, abasic sites, or single-nucleotide gaps further disrupt TRF1 association with telomeric DNA. In vitro DNA binding assays with defined oxidatively damaged telomeric substrates Nucleic acids research High 15731343
2004 Telomere-bound TRF1 (and TRF2) stall replication fork progression at telomeric repeats in vitro; TRF1 overexpression in HeLa cells accumulates cells with 4N DNA content and increases overlap of replication foci with telomere signals, indicating TRF1 inhibits replication fork progression at telomeres. In vitro SV40 replication assay with recombinant TRF1/TRF2, flow cytometry, cytological analysis of replication foci Nucleic acids research High 15007108
2006 Nucleostemin (NS) interacts with TRF1 and enhances TRF1 protein degradation (but not ubiquitination), negatively regulating TRF1 stability and thereby influencing telomere length regulation. Co-immunoprecipitation, protein stability assays, NS gain/loss-of-function mouse models and MEF cultures Molecular and cellular biology Medium 17000763
2009 GNL3L (a GTP-binding protein) interacts with TRF1 in the nucleoplasm, promotes TRF1 homodimerization and telomeric association, prevents PML body recruitment of telomere-bound TRF1, and stabilizes TRF1 by inhibiting its ubiquitylation and binding to the E3 ubiquitin ligase FBX4; GNL3L-mediated TRF1 stabilization is required for mitotic increase of TRF1 and promotes metaphase-to-anaphase transition. Co-immunoprecipitation, ubiquitylation assays, protein stability assays, cell cycle analysis, knockdown experiments The Journal of cell biology High 19487455
2003 Conditional deletion of TRF1 in mouse embryonic stem cells causes growth defects, chromosomal instability, loss of TIN2 and TRF2 telomeric association, abnormal telomere signals, and accumulation of end-to-end fusions with detectable telomere signals at fusion points, without immediate telomere shortening. Conditional knockout in mouse ES cells, telomere FISH, immunofluorescence, chromosomal analysis The Journal of biological chemistry High 14559908
2008 Plk1 (Polo-like kinase 1) phosphorylates TRF1 at Ser-435 in vivo, with Cdk1 serving as a priming kinase to generate the Plk1 docking site; Plk1-mediated phosphorylation dramatically increases TRF1 telomeric DNA binding ability, which reaches a peak during mitosis. Co-immunoprecipitation, in vitro and in vivo kinase assays, phospho-site mutagenesis, cell-cycle-staged DNA binding assays, apoptosis assays The Journal of biological chemistry High 18625707
2009 TRF1 transgenic overexpression in mouse epithelium causes telomere shortening rescued by XPF nuclease deletion, indicating TRF1 negatively regulates telomere length by controlling XPF nuclease activity at telomeres; TRF1 colocalizes with spindle checkpoint proteins BubR1 and Mad2 at mouse telomeres, linking TRF1 to the mitotic spindle checkpoint. Transgenic mouse model (K5TRF1), genetic rescue with XPF knockout, telomere FISH, immunofluorescence colocalization Molecular and cellular biology High 19124610
2006 TRF1 specifically recognizes and binds telomeric binding sites within nucleosomes, forming a stable ternary TRF1-nucleosome-DNA complex; TRF1 binding to nucleosomal telomeric DNA causes alterations in nucleosome structure without dissociating histone subunits, and binding depends on orientation of sites on the nucleosome surface. In vitro reconstitution of ternary complexes, gel shift assays, nucleosome alteration assays Journal of molecular biology High 16756990
2006 Xenopus TRF1 (xTRF1) associates with telomere chromatin specifically in mitosis and dissociates upon mitotic exit; Polo-like kinase (Plx1) phosphorylates xTRF1 in vitro and its immunodepletion impairs mitotic xTRF1-chromatin association, demonstrating cell-cycle-regulated telomere binding controlled by Polo-like kinase. Xenopus egg extract cell-cycle system, chromatin fractionation, in vitro kinase assay, immunodepletion The EMBO journal High 16424898
2017 Nek7 kinase is recruited to telomeres after oxidative DNA damage in an ATM activation-dependent manner and phosphorylates TRF1 at Ser114, preventing TRF1 from binding to Fbx4 (an Skp1-Cul1-F box E3 ligase subunit), thereby blocking proteasomal degradation of TRF1 and maintaining TRF1 association with TIN2 in the shelterin complex. Co-immunoprecipitation, in vitro kinase assay, phospho-site mutagenesis, ubiquitylation assays, telomere damage assays Molecular cell High 28216227
2017 TANKYRASE1 (TNKS1) is recruited to damaged telomeres via direct interaction with TRF1's tankyrase-binding motif (TBM), and subsequently PARylates TRF1 after damage; TNKS1 PARylation of TRF1 is required to recruit repair proteins XRCC1 and polymerase β at damaged telomeres for single-strand break repair (SSBR), protecting genome stability. Co-immunoprecipitation, PARylation assays, TBM mutagenesis, telomere damage assays, recruitment of repair factors assessed by immunofluorescence Nucleic acids research High 28160604
2013 TRF1 is a direct transcriptional target of Oct3/4 in pluripotent stem cells; TRF1 is necessary for both induction and maintenance of pluripotency, and TRF1-high iPSCs show higher pluripotency capacity (teratoma and chimera formation). Knock-in eGFP-TRF1 reporter mouse, ChIP for Oct3/4 at TRF1 promoter, siRNA knockdown during reprogramming, teratoma/chimera assays Nature communications High 23735977
2014 TRF1 depletion abolishes centromeric recruitment of Aurora-B and loosens sister centromere cohesion, resulting in merotelic kinetochore attachments, lagging chromosomes, and micronuclei, causing aneuploidy; a telomere-unbound TRF1 mutant can suppress the knockdown phenotype, indicating this mitotic role is telomere-independent. siRNA knockdown of TRF1, immunofluorescence for Aurora-B centromere localization, chromosome segregation analysis, aneuploidy scoring, rescue with telomere-binding mutant Molecular and cellular biology High 24752893
2017 TERB1 interacts with TRF1 during meiotic prophase through a specific TBM motif; the crystal structure of the TRF1 TRFH domain in complex with the TERB1 TRF1-binding motif was determined; disruption of the TERB1-TRF1 interaction by point mutation in mice causes male-specific infertility with zygotene-pachytene arrest and failure of X-Y chromosome pairing. Crystal structure determination, point mutagenesis knock-in mice, meiotic chromosome analysis, immunofluorescence Nature structural & molecular biology High 29083416
2018 TRF1 counteracts TRF2-mediated telomeric R-loop (telR loop) formation: in vitro, TRF2 stimulates invasion of TERRA-like RNA into telomeric dsDNA via its N-terminal basic domain, while TRF1 suppresses this RNA invasion through its N-terminal acidic domain; in vivo, TRF1 depletion or replacement with an acidic domain deletion mutant causes TRF2-induced telR loop accumulation and telomere loss. In vitro RNA invasion assays, domain mutagenesis, in vivo TRF1 depletion, R-loop detection, telomere loss measurement Nature structural & molecular biology High 29358759
2020 TRF1 loss leads to telomere protein composition reorganization, recruitment of DNA damage response factors, PML, BRCA1, and SMC5/6 complex; mTRF1 suppresses TERRA transcription, homologous recombination, and POLD3-dependent break-induced replication at telomeres, thereby preventing illegitimate mitotic DNA recombination. Proteomic analysis of telomere composition by MS, HR and BIR assays, TERRA quantification, TRF1 deletion in mouse eLife High 31934863
2002 Pin2/TRF1 interacts with EB1 (a microtubule plus-end binding protein) both in vitro and in vivo; they co-localize at the mitotic spindle; EB1 inhibits Pin2/TRF1-mediated microtubule polymerization in vitro; inhibition of Pin2/TRF1 in ataxia-telangiectasia cells restores their mitotic spindle defect in response to microtubule disruption. Yeast two-hybrid, co-immunoprecipitation, in vitro microtubule polymerization assay, immunofluorescence colocalization, ATM-deficient cell functional assay FEBS letters Medium 11943150
2009 PinX1 regulates TRF1 subcellular localization, forcing TRF1 accumulation in the nucleolus when nucleolar PinX1 is overexpressed; nuclear PinX1 overexpression increases TRF1 binding to telomeres; PinX1 interacts with TRF1 in both nucleolus and nucleoplasm. Transfection/co-localization experiments, immunofluorescence, chromatin immunoprecipitation, mutant analysis of PinX1 domains Journal of molecular biology Medium 19265708
2012 PinX1 depletion leads to TRF1 ubiquitination and proteasomal degradation, reducing TRF1 telomere association and triggering telomere DNA damage responses; hTERT plays dual roles—its presence is required for PinX1-mediated TRF1 stabilization, but combined knockdown of PinX1 and hTERT paradoxically stabilizes TRF1. siRNA knockdown, ubiquitylation assays, co-immunoprecipitation, telomere immunofluorescence, chromosome instability analysis The Journal of biological chemistry Medium 24415760
2012 PinX1 associates with telomeres primarily during mitosis and stabilizes TRF1 on telomeres at this stage; PinX1 knockdown reduces TRF1 accumulation on telomeres during mitosis and delays mitotic entry. Endogenous PinX1 localization by cell cycle fractionation and immunofluorescence, siRNA knockdown with mitotic phenotype analysis Molecular and cellular biology Medium 22331467
2019 Condensin II subunit NCAPH2 interacts with TRF1 and co-localizes at telomeres; NCAPH2 depletion causes ATR-dependent DNA damage at telomeres, fragile telomere phenotype, and apparent sister-telomere fusions, indicating NCAPH2 promotes telomere stability through interaction with TRF1. Co-immunoprecipitation, immunofluorescence colocalization, siRNA knockdown with telomere FISH and damage marker analysis Journal of cellular physiology Medium 31026066
2017 Aurora Kinase B (AURKB) localizes to telomeres in mouse embryonic stem cells, interacts with TRF1, and phosphorylates TRF1 at Serine 404 in vitro; loss of AURKB function reduces TRF1 telomere binding, and overexpression of S404-mutant TRF1 causes fragile telomere formation. Immunofluorescence colocalization, co-immunoprecipitation, in vitro kinase assay with mass spectrometry, phospho-site mutagenesis overexpression, telomere fragility assay Nucleic acids research High 29040668
2014 TRF1 promotes Rad51-mediated telomeric D-loop formation in vitro, suggesting a role in facilitating homologous recombination-mediated replication fork restart at telomeres; TRF2 inhibits Rad51-mediated telomeric D-loop formation by occupying the telomeric template. Fluorescent D-loop assay in vitro with purified TRF1, TRF2, and Rad51 Biochemistry Medium 25115914
2023 PARP1 interacts with TRF1 and PARylates it during S-phase, modifying TRF1's DNA affinity; pharmacological or genetic inhibition of PARP1 impairs dynamic TRF1 telomere association, reduces BrdU incorporation at replicating telomeres, and impairs recruitment of WRN and BLM helicases to TRF1-containing complexes during S-phase, causing replication-dependent DNA damage and telomere fragility. Co-immunoprecipitation, PARylation assays, PARP1 inhibition/KO, telomere BrdU incorporation, protein complex analysis by co-IP, telomere fragility assessment Communications biology High 36864251

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Intracellular trafficking and proteolysis of the Arabidopsis auxin-efflux facilitator PIN2 are involved in root gravitropism. Nature cell biology 482 16489343
2008 Differential degradation of PIN2 auxin efflux carrier by retromer-dependent vacuolar targeting. Proceedings of the National Academy of Sciences of the United States of America 319 19004783
1997 TRF1 is a dimer and bends telomeric DNA. The EMBO journal 270 9130722
2001 The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell 266 11701125
2004 TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. The Journal of biological chemistry 260 15316005
1988 T cell-replacing factor (TRF)/interleukin 5 (IL-5): molecular and functional properties. Immunological reviews 229 3284812
2005 Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2. Nucleic acids research 224 15731343
2017 tRF/miR-1280 Suppresses Stem Cell-like Cells and Metastasis in Colorectal Cancer. Cancer research 219 28446464
2012 Lysine63-linked ubiquitylation of PIN2 auxin carrier protein governs hormonally controlled adaptation of Arabidopsis root growth. Proceedings of the National Academy of Sciences of the United States of America 172 22556266
1997 Transcription properties of a cell type-specific TATA-binding protein, TRF. Cell 150 9335336
2012 COP1 mediates the coordination of root and shoot growth by light through modulation of PIN1- and PIN2-dependent auxin transport in Arabidopsis. Development (Cambridge, England) 138 22912415
2019 Angiogenin generates specific stress-induced tRNA halves and is not involved in tRF-3-mediated gene silencing. The Journal of biological chemistry 133 31582561
2021 5'-tRF-GlyGCC: a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis. Genome medicine 105 33563322
2009 PINOID kinase regulates root gravitropism through modulation of PIN2-dependent basipetal auxin transport in Arabidopsis. Plant physiology 102 19363095
1997 TRF1, a mammalian telomeric protein. Trends in genetics : TIG 98 9009844
2003 Importance of TRF1 for functional telomere structure. The Journal of biological chemistry 93 14559908
2022 A novel 3'tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer. Cell death & disease 92 35585048
2006 Nucleostemin delays cellular senescence and negatively regulates TRF1 protein stability. Molecular and cellular biology 92 17000763
2004 Telomere-bound TRF1 and TRF2 stall the replication fork at telomeric repeats. Nucleic acids research 91 15007108
2011 Jasmonate modulates endocytosis and plasma membrane accumulation of the Arabidopsis PIN2 protein. The New phytologist 83 21466556
2004 Tomato TERF1 modulates ethylene response and enhances osmotic stress tolerance by activating expression of downstream genes. FEBS letters 79 15327984
2020 Glucose-TOR signaling regulates PIN2 stability to orchestrate auxin gradient and cell expansion in Arabidopsis root. Proceedings of the National Academy of Sciences of the United States of America 78 33288701
2022 A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer. Journal of hematology & oncology 75 36527118
2021 Inflammatory cytokine-regulated tRNA-derived fragment tRF-21 suppresses pancreatic ductal adenocarcinoma progression. The Journal of clinical investigation 74 34779408
2019 Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter. Nature communications 72 31797871
2013 Inactivation of plasma membrane-localized CDPK-RELATED KINASE5 decelerates PIN2 exocytosis and root gravitropic response in Arabidopsis. The Plant cell 71 23673979
2013 TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells. Nature communications 71 23735977
2021 miRge3.0: a comprehensive microRNA and tRF sequencing analysis pipeline. NAR genomics and bioinformatics 70 34308351
2009 TRF1 controls telomere length and mitotic fidelity in epithelial homeostasis. Molecular and cellular biology 70 19124610
2005 Complex regulation of Arabidopsis AGR1/PIN2-mediated root gravitropic response and basipetal auxin transport by cantharidin-sensitive protein phosphatases. The Plant journal : for cell and molecular biology 70 15807782
2018 TRF1 participates in chromosome end protection by averting TRF2-dependent telomeric R loops. Nature structural & molecular biology 64 29358759
2012 Post-translational modifications of TRF1 and TRF2 and their roles in telomere maintenance. Mechanisms of ageing and development 59 22634377
2023 tRF-Gln-CTG-026 ameliorates liver injury by alleviating global protein synthesis. Signal transduction and targeted therapy 57 37015921
2022 Alveolar macrophage-derived exosomal tRF-22-8BWS7K092 activates Hippo signaling pathway to induce ferroptosis in acute lung injury. International immunopharmacology 54 35299002
2017 Nek7 Protects Telomeres from Oxidative DNA Damage by Phosphorylation and Stabilization of TRF1. Molecular cell 52 28216227
2015 Telomere Restriction Fragment (TRF) Analysis. Bio-protocol 52 27500189
2021 KAI2 promotes Arabidopsis root hair elongation at low external phosphate by controlling local accumulation of AUX1 and PIN2. Current biology : CB 50 34758285
2018 Mechanistic framework for cell-intrinsic re-establishment of PIN2 polarity after cell division. Nature plants 47 30518833
2009 GNL3L stabilizes the TRF1 complex and promotes mitotic transition. The Journal of cell biology 46 19487455
2022 Evaluation of serum tRF-23-Q99P9P9NDD as a potential biomarker for the clinical diagnosis of gastric cancer. Molecular medicine (Cambridge, Mass.) 45 35690737
2016 Ethylene Response Factor TERF1, Regulated by ETHYLENE-INSENSITIVE3-like Factors, Functions in Reactive Oxygen Species (ROS) Scavenging in Tobacco (Nicotiana tabacum L.). Scientific reports 45 27435661
2021 Sphingolipids mediate polar sorting of PIN2 through phosphoinositide consumption at the trans-Golgi network. Nature communications 42 34257291
2016 Effects of Auxins on PIN-FORMED2 (PIN2) Dynamics Are Not Mediated by Inhibiting PIN2 Endocytosis. Plant physiology 42 27506239
2024 Exosome-derived tRNA fragments tRF-GluCTC-0005 promotes pancreatic cancer liver metastasis by activating hepatic stellate cells. Cell death & disease 41 38291031
2017 Telomeric TERB1-TRF1 interaction is crucial for male meiosis. Nature structural & molecular biology 41 29083416
2017 Flavonol-induced changes in PIN2 polarity and auxin transport in the Arabidopsis thaliana rol1-2 mutant require phosphatase activity. Scientific reports 40 28165500
2008 Plk1 phosphorylation of TRF1 is essential for its binding to telomeres. The Journal of biological chemistry 40 18625707
2005 Expressing TERF1 in tobacco enhances drought tolerance and abscisic acid sensitivity during seedling development. Planta 39 15871029
2020 tRFTar: Prediction of tRF-target gene interactions via systemic re-analysis of Argonaute CLIP-seq datasets. Methods (San Diego, Calif.) 37 33045361
2013 PIN2 turnover in Arabidopsis root epidermal cells explored by the photoconvertible protein Dendra2. PloS one 36 23637828
2015 Differential Roles of PIN1 and PIN2 in Root Meristem Maintenance Under Low-B Conditions in Arabidopsis thaliana. Plant & cell physiology 35 25814435
2015 Arabidopsis response to low-phosphate conditions includes active changes in actin filaments and PIN2 polarization and is dependent on strigolactone signalling. Journal of experimental botany 34 25609825
2021 Gly-tRF enhances LCSC-like properties and promotes HCC cells migration by targeting NDFIP2. Cancer cell international 33 34537070
2020 TRF1 averts chromatin remodelling, recombination and replication dependent-break induced replication at mouse telomeres. eLife 32 31934863
2017 A generic Transcriptomics Reporting Framework (TRF) for 'omics data processing and analysis. Regulatory toxicology and pharmacology : RTP 31 29113939
2003 Role of Pin2/TRF1 in telomere maintenance and cell cycle control. Journal of cellular biochemistry 31 12682905
2002 Involvement of the telomeric protein Pin2/TRF1 in the regulation of the mitotic spindle. FEBS letters 31 11943150
2022 tRF-19-W4PU732S promotes breast cancer cell malignant activity by targeting inhibition of RPL27A (ribosomal protein-L27A). Bioengineered 30 35030975
2014 TRF1 ensures the centromeric function of Aurora-B and proper chromosome segregation. Molecular and cellular biology 30 24752893
2022 The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway. Journal of translational medicine 29 35287671
2006 The human telomeric protein TRF1 specifically recognizes nucleosomal binding sites and alters nucleosome structure. Journal of molecular biology 29 16756990
2021 Nitrate triggered phosphoproteome changes and a PIN2 phosphosite modulating root system architecture. EMBO reports 28 34357701
2024 tRF-33-P4R8YP9LON4VDP inhibits gastric cancer progression via modulating STAT3 signaling pathway in an AGO2-dependent manner. Oncogene 26 38783100
2017 Tankyrase1-mediated poly(ADP-ribosyl)ation of TRF1 maintains cell survival after telomeric DNA damage. Nucleic acids research 26 28160604
2016 Trypanosoma brucei TIF2 and TRF Suppress VSG Switching Using Overlapping and Independent Mechanisms. PloS one 25 27258069
2023 PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment. Communications biology 24 36864251
2014 The prion-like domain in the exomer-dependent cargo Pin2 serves as a trans-Golgi retention motif. Cell reports 24 24656818
2023 Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer. Cancers 23 36765853
2022 The biological behavior of tRNA-derived fragment tRF-Leu-AAG in pancreatic cancer cells. Bioengineered 23 35442152
2023 Targeting choroidal vasculopathy via up-regulation of tRNA-derived fragment tRF-22 expression for controlling progression of myopia. Journal of translational medicine 22 37355654
2023 Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2. Journal of cellular and molecular medicine 21 37488774
2019 Condensin II subunit NCAPH2 associates with shelterin protein TRF1 and is required for telomere stability. Journal of cellular physiology 21 31026066
2009 Human PinX1 mediates TRF1 accumulation in nucleolus and enhances TRF1 binding to telomeres. Journal of molecular biology 21 19265708
2006 Cell-cycle-dependent Xenopus TRF1 recruitment to telomere chromatin regulated by Polo-like kinase. The EMBO journal 21 16424898
2023 Hyperglycemia-regulated tRNA-derived fragment tRF-3001a propels neurovascular dysfunction in diabetic mice. Cell reports. Medicine 20 37757825
2022 tRNA-derived fragment tRF-1001: A novel anti-angiogenic factor in pathological ocular angiogenesis. Molecular therapy. Nucleic acids 20 36381574
2020 Mucosal immunity and tRNA, tRF, and tiRNA. Journal of molecular medicine (Berlin, Germany) 20 33200232
2024 Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB. Journal of Zhejiang University. Science. B 19 38725342
2022 tRNA-derived fragment tRF-Glu49 inhibits cell proliferation, migration and invasion in cervical cancer by targeting FGL1. Oncology letters 19 36039056
2021 The AtCRK5 Protein Kinase Is Required to Maintain the ROS NO Balance Affecting the PIN2-Mediated Root Gravitropic Response in Arabidopsis. International journal of molecular sciences 19 34205973
2017 Aurora Kinase B, a novel regulator of TERF1 binding and telomeric integrity. Nucleic acids research 19 29040668
2017 Excessive Cellular S-nitrosothiol Impairs Endocytosis of Auxin Efflux Transporter PIN2. Frontiers in plant science 19 29218054
2012 PinX1 localizes to telomeres and stabilizes TRF1 at mitosis. Molecular and cellular biology 19 22331467
2024 o8G Site-Specifically Modified tRF-1-AspGTC: A Novel Therapeutic Target and Biomarker for Pulmonary Hypertension. Circulation research 18 38747146
2021 Abscisic acid employs NRP-dependent PIN2 vacuolar degradation to suppress auxin-mediated primary root elongation in Arabidopsis. The New phytologist 18 34618941
2024 tRF-His-GTG-1 enhances NETs formation and interferon-α production in lupus by extracellular vesicle. Cell communication and signaling : CCS 17 38972975
2021 Electrophysiological study of Arabidopsis ABCB4 and PIN2 auxin transporters: Evidence of auxin activation and interaction enhancing auxin selectivity. Plant direct 17 34816076
2021 Circulatory exosomal tRF-Glu-CTC-005 and tRF-Gly-GCC-002 serve as predictive factors of successful microdissection testicular sperm extraction in patients with nonobstructive azoospermia. Fertility and sterility 17 34955241
2014 PinX1, a telomere repeat-binding factor 1 (TRF1)-interacting protein, maintains telomere integrity by modulating TRF1 homeostasis, the process in which human telomerase reverse Transcriptase (hTERT) plays dual roles. The Journal of biological chemistry 17 24415760
2024 Activated neutrophil membrane-coated tRF-Gly-CCC nanoparticles for the treatment of aortic dissection/aneurysm. Journal of controlled release : official journal of the Controlled Release Society 16 39672274
2022 Potential "Therapeutic" Effects of Tocotrienol-Rich Fraction (TRF) and Carotene "Against" Bleomycin-Induced Pulmonary Fibrosis in Rats via TGF-β/Smad, PI3K/Akt/mTOR and NF-κB Signaling Pathways. Nutrients 16 35268069
2022 tRNA-derived small RNA 3'U-tRFValCAC promotes tumour migration and early progression in ovarian cancer. European journal of cancer (Oxford, England : 1990) 16 36599181
2019 Biophysical characterization of the insertion of two potent antimicrobial peptides-Pin2 and its variant Pin2[GVG] in biological model membranes. Biochimica et biophysica acta. Biomembranes 16 31682816
2014 TRF1 and TRF2 differentially modulate Rad51-mediated telomeric and nontelomeric displacement loop formation in vitro. Biochemistry 16 25115914
2024 Transfer RNA derived fragment, tRF-Glu-CTC, aggravates the development of neovascular age-related macular degeneration. Theranostics 15 38389841
2020 NRT1.1-Mediated Nitrate Suppression of Root Coiling Relies on PIN2- and AUX1-Mediated Auxin Transport. Frontiers in plant science 15 32582237
2025 TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis. Clinical epigenetics 14 39838504
2023 Boron supply restores aluminum-blocked auxin transport by the modulation of PIN2 trafficking in the root apical transition zone. The Plant journal : for cell and molecular biology 14 36721978
2022 tRNA-derived fragment tRF-1020 ameliorates diabetes-induced retinal microvascular complications. Journal of cellular and molecular medicine 14 36128646
2021 The Diverse Transformer (Trf) Protein Family in the Sea Urchin Paracentrotus lividus Acts through a Collaboration between Cellular and Humoral Immune Effector Arms. International journal of molecular sciences 14 34206148