Affinage

TRIM71

E3 ubiquitin-protein ligase TRIM71 · UniProt Q2Q1W2

Length
868 aa
Mass
93.4 kDa
Annotated
2026-06-10
66 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM71/LIN-41 is a conserved TRIM-NHL protein that controls developmental timing, stem cell self-renewal, and cell fate as a bifunctional post-transcriptional regulator, acting genetically downstream of let-7 miRNA and upstream of differentiation effectors (PMID:10882102, PMID:33599613). Its NHL domain is necessary and sufficient for RNA target recognition, binding structured stem-loop hairpin motifs through conserved residues defined by crystal structures of the NHL domain bound to Trincr1 and CDKN1A RNA (PMID:23125361, PMID:38036331, PMID:40180090). The position of the bound site dictates the silencing mode: 3'UTR binding drives mRNA decay while 5'UTR binding causes translational repression, a rule established by binding-site transplantation (PMID:28111013). Through this activity TRIM71 represses a broad target set including CDKN1A/p21 — which it silences via an NMD-dependent (SMG1/UPF1/SMG7) route to promote the G1-S transition — AGO2, EGR1, Rbl1/2, MBNL1, and Hmga2, thereby reinforcing stemness and shaping the transcriptome and splicing landscape (PMID:22735451, PMID:23125361, PMID:24239284, PMID:31732746, PMID:31371437, PMID:33599613, PMID:37492931). A second, RING-dependent E3 ubiquitin ligase activity targets AGO2, p53 and mutant p53, Lin28B, and RAF1 for ubiquitination, linking TRIM71 to let-7 biogenesis, apoptosis/differentiation control, and MAPK signaling (PMID:19898466, PMID:24602972, PMID:28430184, PMID:31570706, PMID:36244648). TRIM71 acts on let-7 by two routes — promoting pre-let-7 degradation with LIN28/TUT4 and repressing mature let-7 via AGO2/RISC — forming a bistable feedback loop with the miRNA (PMID:33599613, PMID:33975917). TRIM71 abundance is itself controlled by CDK-1/SCF-SEL-10 phosphodegron-dependent degradation during meiotic maturation and by Pfkp-mediated serine phosphorylation that blocks autoubiquitination (PMID:30206186, PMID:36660859). De novo NHL-domain variants cause congenital hydrocephalus by altering RNA substrate specificity — gain-of-function mutants such as R595H and R783H bind ectopic targets (β-catenin, Lsd1) and impair CDKN1A binding and P-body localization (PMID:36573342, PMID:36757932, PMID:38833623).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Established the genetic placement of LIN-41 in the heterochronic pathway, defining it as the developmental-timing effector acting downstream of let-7 and upstream of LIN-29.

    Evidence Genetic epistasis and GFP reporter imaging in C. elegans

    PMID:10882102

    Open questions at the time
    • Did not show direct miRNA-target binding
    • Molecular activity of LIN-41 protein unknown at this stage
  2. 2004 High

    Demonstrated direct let-7 binding to the lin-41 3'UTR through two complementary sites, providing the biochemical basis for the genetic repression.

    Evidence In vitro RNA binding, in vivo compensatory mutagenesis, luciferase reporters

    PMID:14729570

    Open questions at the time
    • Structural basis of the interaction not resolved
    • Did not address LIN-41's own activity as a regulator
  3. 2008 High

    Resolved the structural basis of the let-7:lin-41 interaction at LCS2 and LCS1, revealing non-canonical stem-loop features.

    Evidence NMR solution structures of the miRNA:mRNA complexes

    PMID:18296482 PMID:20660479

    Open questions at the time
    • Structures describe the miRNA-target duplex, not TRIM71 protein-RNA recognition
    • Functional consequence of conformational differences not tested
  4. 2009 High

    Revealed that LIN41 is itself an E3 ubiquitin ligase that ubiquitinates AGO2 and localizes to P-bodies, recasting it from a passive miRNA target into an active regulator of the miRNA machinery.

    Evidence In vitro ubiquitylation, reciprocal co-IP, P-body colocalization, gain/loss-of-function western blot in mouse

    PMID:19898466

    Open questions at the time
    • Did not establish RNA-binding/repressor activity
    • Physiological ubiquitination substrate scope unknown
  5. 2012 High

    Separated TRIM71's two activities, showing the NHL domain mediates RNA binding/repression while the RING domain is dispensable for mRNA silencing, and linked CDKN1A repression to ESC cell-cycle progression.

    Evidence Domain-deletion mutagenesis, reporter repression, mRNA decay assays, KD/rescue with cell cycle analysis (two studies)

    PMID:22735451 PMID:23125361

    Open questions at the time
    • RNA motif recognized by NHL not yet defined
    • Mechanism of decay vs translational repression unresolved
  6. 2013 Medium

    Extended the repressor role to reprogramming, identifying EGR1 as a translationally repressed target within the let-7/LIN-41 axis.

    Evidence mRNA binding and translational reporter assays during reprogramming

    PMID:24239284

    Open questions at the time
    • Single lab
    • Direct binding motif on EGR1 not mapped
  7. 2014 High

    Defined germline and reprogramming roles: LIN-41 controls oocyte meiotic maturation via translational repression, ubiquitinates Lin28B to promote let-7, and uses distinct mechanisms in soma vs germline.

    Evidence C. elegans null/domain mutants, immunofluorescence, epistasis; human Co-IP, in vivo ubiquitination, domain mapping

    PMID:24602972 PMID:25167051 PMID:25261698

    Open questions at the time
    • Molecular basis of germline-vs-soma mechanistic divergence unresolved
    • Lin28B ubiquitination findings single lab
  8. 2017 High

    Established the position-dependent silencing rule and the in vivo RNP composition, and added p53 ubiquitination as a route by which TRIM71 antagonizes apoptosis/differentiation.

    Evidence Ribosome profiling, RIP, binding-site transplantation; RNP purification with MS; Co-IP, ubiquitination, mouse KO with neural tube phenotype

    PMID:28111013 PMID:28430184 PMID:28576864

    Open questions at the time
    • How site position is mechanistically read out by effectors not fully defined
    • p53 ubiquitination substrate determinants partially characterized
  9. 2018 High

    Defined the SCF-SEL-10/CDK-1 phosphodegron pathway controlling LIN-41 turnover, explaining how its activity is temporally switched off at meiotic maturation.

    Evidence Phosphodegron mutagenesis and domain transplantation, CDK-1/SEL-10 genetics in C. elegans

    PMID:30206186

    Open questions at the time
    • Direct kinase phosphorylating the degrons not identified in this work
    • Conservation of this degron control in mammals untested here
  10. 2019 High

    Demonstrated that NHL recognizes structured 3'UTR hairpins to drive decay genome-wide, that CDKN1A repression operates through an NMD (SMG1/UPF1/SMG7) axis independent of miRNAs, and connected TRIM71 to splicing (MBNL1), FGF/ERK (Trincr1/SHCBP1), and mutant p53 degradation.

    Evidence RIP-seq/RNA-seq, NHL domain assays, NMD-factor knockdown, lncRNA Co-IP/rescue, mutant-p53 ubiquitination

    PMID:30911006 PMID:31371437 PMID:31570706 PMID:31732746

    Open questions at the time
    • How NMD machinery is recruited by TRIM71 not structurally defined
    • Trincr1 and mutant-p53 findings single lab
  11. 2021 High

    Resolved the dual mechanism by which TRIM71 controls let-7: translational repression of AGO2 mRNA plus LIN28/TUT4-dependent pre-let-7 degradation and RISC-dependent target stabilization, supporting a bistable switch.

    Evidence Polysome profiling, let-7 quantification, pre-let-7 processing and RISC interaction assays, rescue (two studies)

    PMID:33599613 PMID:33975917

    Open questions at the time
    • Quantitative thresholds of the bistable switch not modeled experimentally
    • Interplay between the two let-7 routes in vivo unresolved
  12. 2022 Medium

    Expanded the ligase substrate set to RAF1 and showed substrate access is competed by HDLBP, linking TRIM71 to MAPK signaling control, alongside Pfkp-mediated stabilizing phosphorylation.

    Evidence MS screen, Co-IP competition, ubiquitination/proteasome assays; in vitro kinase and autoubiquitination assays

    PMID:36244648 PMID:36660859

    Open questions at the time
    • Single-lab biochemistry for each
    • In vivo relevance of HDLBP competition and Pfkp phosphorylation not genetically established
  13. 2023 High

    Provided crystal structures of the NHL domain bound to RNA, defined the determinants of motif recognition, and showed that congenital-hydrocephalus mutations are gain-of-function that retarget TRIM71 to ectopic mRNAs (β-catenin, Lsd1) while impairing canonical CDKN1A binding.

    Evidence X-ray crystallography with mutagenesis and RIP; PAR-CLIP/RIP target ID, translation reporters, target-specific rescue; IMP1 Co-IP/RIP-seq; cochlear organoid domain mutants

    PMID:32816599 PMID:36573342 PMID:36757932 PMID:37492931 PMID:37670562 PMID:38036331 PMID:40180090

    Open questions at the time
    • Structure of the RING/E3 module and its substrate engagement not solved
    • How single NHL substitutions create new specificities mechanistically unresolved
  14. 2024 Medium

    Linked TRIM71 NHL variants causally to human congenital hydrocephalus via impaired CDKN1A binding and disrupted P-body localization, and identified an m6A/IGF2BP1-dependent mRNA-stabilizing role in liver cancer.

    Evidence Exome sequencing with family validation, functional binding/localization assays, single-cell transcriptomics; Co-IP, RIP, m6A pharmacology

    PMID:38833623 PMID:39267787

    Open questions at the time
    • m6A-dependent stabilization mechanism single lab
    • How loss-of-binding vs gain-of-function variants converge on the same disease unresolved
  15. 2025 High

    Defined developmental in vivo target programs: TRIM71 restricts TGFβ-type signaling (Inhba/Tgfbr2) to maintain cochlear progenitors and represses Eomes to permit proper gastrulation and primitive erythropoiesis.

    Evidence Conditional/global KO mice, scRNA-seq, NHL repression assays, genetic epistasis

    PMID:39909558 PMID:40892928

    Open questions at the time
    • Eomes findings single lab
    • Relative contribution of decay vs translational repression for these targets in vivo not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRIM71's RNA-binding and E3-ligase activities are coordinated on shared substrates (e.g., AGO2 mRNA vs AGO2 protein), and how its abundance and substrate specificity are integrated by upstream signals across tissues, remains unresolved.
  • No structure of full-length TRIM71 or its RING-substrate complexes
  • Mechanism switching between mRNA stabilization and repression not defined
  • Integration of phosphorylation, degron control, and lncRNA inhibition in vivo unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0016874 ligase activity 6 GO:0045182 translation regulator activity 5 GO:0140096 catalytic activity, acting on a protein 5 GO:0140098 catalytic activity, acting on RNA 4
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 2
Partners
AGO2HDLBPIGF2BP1IMP1LIN28BP53RAF1TUT4
Complex memberships
P-bodyRISC (TRIM71-AGO2 RNP)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 C. elegans LIN-41 acts in the heterochronic pathway downstream of let-7 miRNA and upstream of LIN-29 transcription factor; let-7 mutations cause reiterated heterochronic phenotypes that are suppressed by lin-41 mutations, establishing genetic epistasis. A lin-41::GFP fusion is downregulated at the time let-7 is upregulated, and the lin-41 3'UTR contains two elements complementary to let-7. Genetic epistasis (suppressor screen, double-mutant analysis), GFP reporter fusion imaging Molecular cell High 10882102
2004 let-7 miRNA directly binds the lin-41 3'UTR in vitro via two conserved let-7 complementary sites (LCS1 and LCS2); compensatory mutations in LCS sites that match the let-7(n2853) lesion partially restore lin-41 3'UTR function in vivo, providing direct experimental evidence for miRNA-target binding. In vitro RNA-binding assay, compensatory mutation analysis in vivo, luciferase reporter assay Genes & development High 14729570
2008 NMR solution structure of the let-7 miRNA:lin-41 mRNA complex at LCS2 reveals a stem-loop with two stem regions separated by an asymmetric internal loop; three uracils form a base triple and two adenines form a base pair in the internal loop, defining structural basis of miRNA-target interaction. NMR spectroscopy with NOE restraints, torsion angle restraints, and residual dipolar couplings Nucleic acids research High 18296482
2010 NMR solution structure of the let-7:lin-41 complex at LCS1 reveals a stem-loop with non-canonical structural elements (asymmetric internal loop, adenine bulge) within the seed region; comparison with LCS2 structure shows conformational differences correlating with distinct bending between stems. NMR spectroscopy (solution-state) Nucleic acids research High 20660479
2009 Mouse LIN41 (mLin41) acts as an E3 ubiquitin ligase that mediates ubiquitylation of AGO2 in vitro and in vivo; mLin41 interacts with Dicer and Argonaute proteins (Ago1, Ago2, Ago4) via co-precipitation; it colocalizes with P-body markers, Ago2, Mov10, and Tnrc6b in cytoplasmic foci. Overexpression/depletion of mLin41 inversely changes Ago2 protein levels, implicating mLin41 in Ago2 turnover. mLin41 cooperates with Lin-28 to suppress let-7 activity. In vitro ubiquitylation assay, co-immunoprecipitation, immunofluorescence colocalization, overexpression/knockdown with western blot Nature cell biology High 19898466
2012 TRIM71 associates with AGO2 and microRNAs and represses expression of CDKN1A (p21), a CDK inhibitor; this repression requires the RING domain and specific protein domains for P-body localization. TRIM71 knockdown prolongs G1 phase and slows ESC proliferation, phenotype rescued by CDKN1A depletion, demonstrating TRIM71 promotes G1-S transition via CDKN1A repression. Co-immunoprecipitation, reporter mRNA repression assay, knockdown/rescue experiments, cell cycle analysis (FACS), P-body localization by immunofluorescence Nature communications High 22735451
2012 TRIM71 promotes translational repression and mRNA decay; the NHL domain is necessary and sufficient to target TRIM71 to RNA, while the RING domain (ubiquitin ligase activity) is dispensable for mRNA repression. Rbl1 and Rbl2 are identified as TRIM71 target mRNAs in mouse ESCs. RNA-association assays, translational repression reporter assays, domain deletion mutagenesis, mRNA decay assays Nucleic acids research High 23125361
2013 LIN-41 inhibits translation of EGR1 mRNA through binding its cognate mRNA, as part of a let-7/LIN-41 pathway that controls reprogramming; LIN41 regulates a broad array of differentiation genes post-transcriptionally. Mechanistic studies including mRNA binding assays and translational reporter analysis, knockdown/overexpression during reprogramming Cell stem cell Medium 24239284
2014 Human TRIM71 ubiquitinates Lin28B and promotes its proteasomal degradation; the N-terminal RING finger motif of TRIM71 is critical for Lin28B interaction and polyubiquitination. The C-terminal ~50 amino acid stretch unique to Lin28B (vs Lin28A) is essential for TRIM71 interaction. TRIM71-mediated Lin28B degradation consequently promotes let-7 expression. Co-immunoprecipitation, in vivo ubiquitination assay, knockdown experiments, domain mapping/mutagenesis Biochimica et biophysica acta Medium 24602972
2014 C. elegans LIN-41 is a translational repressor that controls oocyte growth and meiotic maturation; lin-41 null mutants display premature pachytene cellularization, CDK-1 activation, M-phase entry, and spindle assembly. Translational derepression of CDC-25.3 (CDK-1 activator) contributes to premature M-phase entry. LIN-41 and OMA-1/2 have an antagonistic relationship controlling meiotic maturation. Genetic null mutant analysis, immunofluorescence (spindle assembly), genetic epistasis Genetics High 25261698
2014 C. elegans LIN-41 controls onset of developmental plasticity in the germline; LIN-41 is expressed in oocyte cytoplasm and mutations in its predicted RNA-association domain have only minor germline effects (unlike somatic effects), suggesting LIN-41 functions via different molecular mechanisms in germline vs soma. Structure-function analysis with domain mutations, genetic screens, oocyte phenotype analysis PLoS genetics Medium 25167051
2017 C. elegans LIN41 has two distinct mRNA-silencing activities determined by binding site position: 3'UTR binding leads to mRNA decay of targets mab-10, mab-3, and dmd-3, while 5'UTR binding of the lin-29A isoform causes translational repression. Binding site transplantation experiments demonstrated that the location of the LIN41 binding site specifies the silencing mechanism. Genome-wide ribosome profiling, RNA immunoprecipitation, in vitro binding, binding site transplantation experiments Molecular cell High 28111013
2017 LIN41/TRIM71 interacts with p53, controls p53 abundance by ubiquitination, and antagonizes p53-dependent pro-apoptotic and pro-differentiation responses during stem cell differentiation. In vivo, lack of LIN41 is associated with upregulation of Grhl3 and widespread caspase-3 activation (p53 effectors). Lin41-deficient mice display neural tube closure defects. Co-immunoprecipitation, ubiquitination assay, Lin41-inducible mouse ESCs, ubiquitin/ubiquitin-like modification proteomics, in vivo knockout analysis Cell death and differentiation High 28430184
2017 LIN-41-containing RNPs in C. elegans include essential RNA-binding proteins, the GLD-2 cytoplasmic poly(A) polymerase, the CCR4-NOT deadenylase complex, and translation initiation factors. LIN-41 represses translation of spn-4 and meg-1 mRNAs while OMA-1/2 promote their expression, defining a translational repression-to-activation switch during oocyte meiotic maturation. RNP purification, mass spectrometry protein identification, RNA sequencing of RNP-associated mRNAs, genetic analysis Genetics High 28576864
2018 C. elegans LIN-41 degradation upon meiotic maturation requires CDK-1 activity and the SCF E3 ubiquitin ligase subunit SEL-10/Fbw7/Cdc4. Two nonoverlapping protein regions (Deg-A and Deg-B) each containing phosphodegron sequences are individually necessary for LIN-41 degradation; Deg-A and Deg-B together are sufficient to confer SEL-10-dependent degradation when transplanted to a different oocyte protein. Domain deletion/transplantation experiments, CDK-1 and SEL-10 loss-of-function genetics, phosphodegron mutagenesis Genetics High 30206186
2019 TRIM71 represses CDKN1A/p21 mRNA via direct interaction of its NHL domain with a structural RNA stem-loop motif in the CDKN1A 3'UTR. This repression is independent of miRNA-mediated silencing and instead requires the NMD factors SMG1, UPF1, and SMG7 (TRIM71/NMD axis). RNA immunoprecipitation, NHL domain binding assay, miRNA-independent reporter assay, knockdown of NMD factors, mRNA decay assays Nucleic acids research High 31732746
2019 The lncRNA Trincr1 binds TRIM71 in the cytoplasm and represses it, leading to downregulation of SHCBP1 protein and decreased FGF/ERK signaling in mouse ESCs. Trim71 knockdown completely rescues the defects of Trincr1 knockout, placing TRIM71 downstream of Trincr1 in the FGF/ERK regulatory pathway. RNA immunoprecipitation, Co-IP, knockout/knockdown rescue experiments, phospho-ERK western blot Nature communications Medium 30911006
2019 TRIM71 functions as an E3 ubiquitin ligase for mutant p53; TRIM71 binds the transactivation domain of mutant p53 and induces its ubiquitination and proteasomal degradation, inhibiting mutant p53 GOF target gene expression. Co-immunoprecipitation, in vivo ubiquitination assay, proteasome inhibitor experiments, gene expression analysis Cell death & disease Medium 31570706
2019 TRIM71 shapes mESC transcriptome predominantly through RNA-binding activity; it binds targets through 3'UTR hairpin motifs and acts predominantly by target mRNA degradation. TRIM71 represses MBNL1, and through MBNL1 repression promotes embryonic alternative splicing patterns. CH-associated mutations in the NHL domain impair target silencing. RNA-seq, RIP-seq, domain mutant analysis, alternative splicing analysis, functional NHL mutation characterization Genes & development High 31371437
2021 TRIM71 represses AGO2 mRNA translation in mouse embryonic stem cells. Blocking this repression leads to a post-transcriptional increase of mature let-7 microRNAs, resulting in let-7-dependent stemness defects and accelerated differentiation, supporting a Trim71-let-7 bistable switch model. Polysome profiling/translation assay, let-7 quantification, knockdown/rescue experiments with stemness markers eLife High 33599613
2021 TRIM71 regulates let-7 activity via two independent mechanisms: (1) enhancement of pre-let-7 degradation through direct interaction with LIN28 and TUT4 (inhibiting let-7 maturation), and (2) repression of mature let-7 activity via RNA-dependent interaction with AGO2/RISC, directly binding and stabilizing let-7 targets. Co-immunoprecipitation, pre-let-7 processing assay, RISC interaction assay, RNA pulldown, transcriptomic analysis RNA (New York, N.Y.) High 33975917
2022 TRIM71 functions as an E3 ubiquitin ligase targeting RAF1 for ubiquitin-proteasome degradation; HDLBP competes with TRIM71 for RAF1 binding and inhibits this degradation, stabilizing RAF1 and maintaining MEKK1-induced RAF1-Ser259-dependent MAPK signaling. Mass spectrometry screen, co-immunoprecipitation, ubiquitination assay, proteasome inhibitor experiments Cellular and molecular gastroenterology and hepatology Medium 36244648
2022 The CH-causing Trim71 R783H mutation alters mRNA substrate specificity: mutant Trim71 binds and represses translation of Lsd1 (Kdm1a) mRNA (not bound by wild-type), causing accelerated stem cell differentiation and neural lineage commitment. Specific inhibition of this Lsd1 repression or slight Lsd1 increase alleviates the defects. PAR-CLIP/RIP to identify mutant-specific targets, translation reporter assay, Lsd1 rescue experiments, neural differentiation assays EMBO reports High 36573342
2023 Crystal structure of the mouse TRIM71 NHL domain in complex with a stem-loop RNA motif from Trincr1 lncRNA was solved; an adenosine base at the loop region is crucial for mTRIM71 interaction. Key conserved residues required for RNA binding were identified by mutagenesis; single-site mutations impair binding to hairpin RNAs in vitro and to CDKN1A and Rbl2 mRNAs in mESCs. CH-specific mutations similarly impair RNA target binding. X-ray crystallography (PDB structure), mutagenesis, in vitro RNA binding assay, RIP in mESCs Science bulletin High 38036331
2023 CH-associated mutations R595H and R783H in Trim71 are gain-of-function: each binds an ectopic and distinct repertoire of target mRNAs. R595H-Trim71, but not R783H-Trim71 or wild-type, binds β-catenin mRNA and represses its translation; increasing β-catenin specifically rescues R595H-Trim71 mESC differentiation defects, implicating distinct Wnt/β-catenin disruption by this mutation. PAR-CLIP/RIP for target identification, translation reporter assay, β-catenin overexpression/Wnt agonist rescue PLoS biology High 36757932
2023 TRIM71 NHL domain crystal structure (PDB: 9JUR) confirms strong and specific binding to CDKN1A mRNA (Kd = 0.42 μM by fluorescence polarization, confirmed by EMSA), establishing the structural basis for CDKN1A mRNA repression. X-ray crystallography, fluorescence polarization binding assay, EMSA International journal of biological macromolecules High 40180090
2023 TRIM71 co-precipitates with IMP1 (an RNA-stabilizing protein), is capable of both positive and negative regulation of target RNAs depending on the target; deletion of the NHL domain impairs RNA binding. RNAs bound by CH-associated NHL point mutations cluster with RNAs bound by the NHL deletion mutant. RNA immunoprecipitation (RIP-seq), co-immunoprecipitation, NHL domain deletion analysis Cell cycle (Georgetown, Tex.) Medium 32816599
2023 TRIM71 RNA-binding activity (NHL domain) is essential for cochlear supporting cell de-differentiation into progenitor-like cells; TRIM71 re-expression increases mitotic and hair-cell-forming potential of P5 cochlear supporting cells. TRIM71 target Hmga2 is essential for supporting cell self-renewal and hair cell formation. Organoid-based assay, domain mutant (RNA-binding-deficient TRIM71), transcriptomic analysis, Hmga2 knockdown EMBO reports Medium 37492931
2023 The glycolytic enzyme Pfkp acts as a protein kinase that phosphorylates Lin41 on serine residues, stabilizing Lin41 by impeding its autoubiquitination and proteasomal degradation; this permits Lin41-mediated mRNA destabilization of ectodermal markers to favor endodermal specification in mESCs. In vitro kinase assay (Pfkp→Lin41 phosphorylation), autoubiquitination assay, mRNA stability assay, ESC differentiation assay EMBO reports Medium 36660859
2024 TRIM71 forms a protein complex with IGF2BP1, binds and stabilizes CEBPA mRNA in an m6A-dependent manner, enhancing serine/glycine metabolic pathway and promoting liver cancer progression. Co-immunoprecipitation, RIP assay, m6A inhibitor experiments, metabolic assays Theranostics Medium 39267787
2024 de novo TRIM71 NHL domain variants causing congenital hydrocephalus exhibit impaired binding to canonical target CDKN1A; other variants fail to direct subcellular localization of TRIM71 to processing bodies. Single-cell transcriptomics confirms TRIM71 expression in first-trimester neural stem cells. Functional binding assay (NHL mutants vs CDKN1A), P-body localization assay, exome sequencing with family validation, single-cell transcriptomics Brain : a journal of neurology Medium 38833623
2025 TRIM71 maintains cochlear hair cell progenitors in a proliferative/undifferentiated state by restricting TGFβ-type signaling; transcriptomic profiling of Trim71-deficient cochlear progenitor cells identifies Inhba and Tgfbr2 as TRIM71 repression targets. Loss of TRIM71 in early otic development causes premature hair cell formation. Conditional knockout mouse model, transcriptomic profiling, double-knockout genetic epistasis (Inhba-Tgfbr1 dKO) Proceedings of the National Academy of Sciences of the United States of America High 40892928
2025 TRIM71 represses Eomes mRNA (a mesodermal pioneer transcription factor) via its NHL domain; global Trim71 KO embryos display impaired primitive erythropoiesis, yolk sac vasculature defects, and strong upregulation of Eomes at gastrulation. Conditional/global knockout mouse, scRNA-seq, NHL domain binding/repression assay for Eomes mRNA Life science alliance Medium 39909558
2023 C. elegans LIN-41 regulates germline mRNAs via LIN-41 Recognition Elements (LREs); cfp-1 mRNA (encoding chromatin modifier CFP-1) was identified and validated as a LRE-dependent germline target whose LIN-41-mediated repression may facilitate transcriptional reprogramming during the oocyte-to-embryo transition. Computational-experimental analysis (LRE motif prediction + experimental validation), RIP, functional assays Nucleic acids research Medium 37670562
2016 TRIM71 ubiquitin transfer activity (E3 ligase function) is required for its tumor suppressive effects on cancer cell proliferation and invasion; overexpression of an ubiquitin transfer-deficient TRIM71 mutant has no effect on proliferation or invasion regardless of Lin28B-let-7-HMGA2 signaling status. Ubiquitin transfer-deficient mutant overexpression, cell proliferation/invasion assays, mouse tumor model Oncotarget Medium 27821801

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Molecular cell 586 10882102
2004 The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3'UTR. Genes & development 374 14729570
2009 The let-7 target gene mouse lin-41 is a stem cell specific E3 ubiquitin ligase for the miRNA pathway protein Ago2. Nature cell biology 190 19898466
2013 The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes. Cell stem cell 189 24239284
2005 Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 139 16247770
2012 Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation. Nature communications 131 22735451
2008 The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure. Cell cycle (Georgetown, Tex.) 110 19098426
2012 The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function. Nucleic acids research 104 23125361
2007 Human TRIM71 and its nematode homologue are targets of let-7 microRNA and its zebrafish orthologue is essential for development. Molecular biology and evolution 75 17890240
2014 The TRIM-NHL protein LIN-41 and the OMA RNA-binding proteins antagonistically control the prophase-to-metaphase transition and growth of Caenorhabditis elegans oocytes. Genetics 69 25261698
2017 LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms. Molecular cell 63 28111013
2014 The TRIM-NHL protein LIN-41 controls the onset of developmental plasticity in Caenorhabditis elegans. PLoS genetics 60 25167051
2017 The ubiquitin ligase LIN41/TRIM71 targets p53 to antagonize cell death and differentiation pathways during stem cell differentiation. Cell death and differentiation 54 28430184
2017 LIN-41 and OMA Ribonucleoprotein Complexes Mediate a Translational Repression-to-Activation Switch Controlling Oocyte Meiotic Maturation and the Oocyte-to-Embryo Transition in Caenorhabditis elegans. Genetics 53 28576864
2013 LIN-41/TRIM71: emancipation of a miRNA target. Genes & development 52 23512656
2005 Analysis of the regulation of lin-41 during chick and mouse limb development. Developmental dynamics : an official publication of the American Association of Anatomists 52 16245339
2019 A TRIM71 binding long noncoding RNA Trincr1 represses FGF/ERK signaling in embryonic stem cells. Nature communications 44 30911006
2019 The mRNA repressor TRIM71 cooperates with Nonsense-Mediated Decay factors to destabilize the mRNA of CDKN1A/p21. Nucleic acids research 41 31732746
2015 Co-existence of intact stemness and priming of neural differentiation programs in mES cells lacking Trim71. Scientific reports 41 26057209
2014 The ubiquitin ligase human TRIM71 regulates let-7 microRNA biogenesis via modulation of Lin28B protein. Biochimica et biophysica acta 40 24602972
2019 Ubiquitin ligase TRIM71 suppresses ovarian tumorigenesis by degrading mutant p53. Cell death & disease 39 31570706
2006 Novel gain-of-function alleles demonstrate a role for the heterochronic gene lin-41 in C. elegans male tail tip morphogenesis. Developmental biology 38 16806150
2019 The RNA hairpin binder TRIM71 modulates alternative splicing by repressing MBNL1. Genes & development 36 31371437
2015 Lin41/Trim71 is essential for mouse development and specifically expressed in postnatal ependymal cells of the brain. Frontiers in cell and developmental biology 36 25883935
2008 Regulation of the Drosophila lin-41 homologue dappled by let-7 reveals conservation of a regulatory mechanism within the LIN-41 subclade. Developmental dynamics : an official publication of the American Association of Anatomists 34 18069688
2006 Cloning and regulation of the vertebrate homologue of lin-41 that functions as a heterochronic gene in Caenorhabditis elegans. Developmental dynamics : an official publication of the American Association of Anatomists 33 16477647
2013 The stem cell E3-ligase Lin-41 promotes liver cancer progression through inhibition of microRNA-mediated gene silencing. The Journal of pathology 32 23097274
2019 NANOG and LIN28 dramatically improve human cell reprogramming by modulating LIN41 and canonical WNT activities. Biology open 30 31806618
2021 Repressing Ago2 mRNA translation by Trim71 maintains pluripotency through inhibiting let-7 microRNAs. eLife 28 33599613
2016 TRIM71 suppresses tumorigenesis via modulation of Lin28B-let-7-HMGA2 signaling. Oncotarget 24 27821801
2021 TRIM71 Deficiency Causes Germ Cell Loss During Mouse Embryogenesis and Is Associated With Human Male Infertility. Frontiers in cell and developmental biology 23 34055789
2010 NMR structure of the let-7 miRNA interacting with the site LCS1 of lin-41 mRNA from Caenorhabditis elegans. Nucleic acids research 23 20660479
2008 Solution structure of a let-7 miRNA:lin-41 mRNA complex from C. elegans. Nucleic acids research 23 18296482
2021 The stem cell-specific protein TRIM71 inhibits maturation and activity of the prodifferentiation miRNA let-7 via two independent molecular mechanisms. RNA (New York, N.Y.) 21 33975917
2019 Trim71/lin-41 Links an Ancient miRNA Pathway to Human Congenital Hydrocephalus. Trends in molecular medicine 21 30975633
2022 HDLBP Promotes Hepatocellular Carcinoma Proliferation and Sorafenib Resistance by Suppressing Trim71-dependent RAF1 Degradation. Cellular and molecular gastroenterology and hepatology 20 36244648
2024 TRIM71 mutations cause a neurodevelopmental syndrome featuring ventriculomegaly and hydrocephalus. Brain : a journal of neurology 15 38833623
2024 Oncofetal TRIM71 drives liver cancer carcinogenesis through remodeling CEBPA-mediated serine/glycine metabolism. Theranostics 15 39267787
2020 mRBPome capture identifies the RNA-binding protein TRIM71, an essential regulator of spermatogonial differentiation. Development (Cambridge, England) 15 32188631
2018 Multiple Mechanisms Inactivate the LIN-41 RNA-Binding Protein To Ensure a Robust Oocyte-to-Embryo Transition in Caenorhabditis elegans. Genetics 14 30206186
2016 LIN-41 inactivation leads to delayed centrosome elimination and abnormal chromosome behavior during female meiosis in Caenorhabditis elegans. Molecular biology of the cell 11 26764090
2021 daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71. PLoS genetics 10 34780472
2020 TRIM71 binds to IMP1 and is capable of positive and negative regulation of target RNAs. Cell cycle (Georgetown, Tex.) 10 32816599
2023 Circ_0007429/miR-637/TRIM71/Ago2 axis participates in the regulation of proliferation, migration, invasion, apoptosis, and aerobic glycolysis of HCC. Molecular carcinogenesis 9 36920046
2023 Molecular mechanism governing RNA-binding property of mammalian TRIM71 protein. Science bulletin 9 38036331
2023 Glycolytic Pfkp acts as a Lin41 protein kinase to promote endodermal differentiation of embryonic stem cells. EMBO reports 8 36660859
2023 Different congenital hydrocephalus-associated mutations in Trim71 impair stem cell differentiation via distinct gain-of-function mechanisms. PLoS biology 8 36757932
2023 TRIM71 reactivation enhances the mitotic and hair cell-forming potential of cochlear supporting cells. EMBO reports 8 37492931
2022 A congenital hydrocephalus-causing mutation in Trim71 induces stem cell defects via inhibiting Lsd1 mRNA translation. EMBO reports 7 36573342
2025 TRIM71 bound hsa-miR-30b-5p restores mitochondrial function in a cellular model of Parkinson's disease. Free radical biology & medicine 3 40398685
2023 Gain-of-function mutations in Trim71 linked to congenital hydrocephalus. PLoS biology 3 36757939
2025 Impaired primitive erythropoiesis and defective vascular development in Trim71-KO embryos. Life science alliance 2 39909558
2024 Mitochondrial E3 ligase TRIM71 affects mitochondrial complex assembly and sensitizes dopaminergic neuronal cells to apoptosis in Parkinson's Disease (PD). The international journal of biochemistry & cell biology 2 39522935
2023 Post-transcriptional repression of CFP-1 expands the regulatory repertoire of LIN-41/TRIM71. Nucleic acids research 2 37670562
2021 Brain-wide identification of LIN-41 (TRIM71) protein-expressing neurons by NeuroPAL. microPublication biology 2 35622497
2025 Human tripartite motif-containing protein 71 NCL-1/HT2A/LIN-41 domain crystal structure and its potential natural inhibitors. International journal of biological macromolecules 1 40180090
2025 The RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development. Proceedings of the National Academy of Sciences of the United States of America 1 40892928
2021 Methylglyoxal influences development of Caenorhabditis elegans via lin-41-dependent pathway. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 1 33901606
2017 When LIN41 Comes to a Fork in the Road, It Takes BOTH Paths: Translational Repression OR mRNA Decay, Depending on the Target Site Position. Molecular cell 1 28157501
2026 Structural basis and pathological function of TRIM71: An analysis based on the TRIM-NHL subfamily. Biochemical pharmacology 0 42119823
2026 West Nile Virus inhibits type I interferon response via TRIM71 in human microglial cells. Antiviral research 0 42177918
2026 TRIM71 suppresses cervical cancer progression by inhibiting Nectin4-mediated Wnt/β-catenin signaling. Biology direct 0 42237330
2025 The RNA-binding protein TRIM71 is essential for hearing in humans and mice and regulates the timing of auditory sensory organ development. bioRxiv : the preprint server for biology 0 40501610
2024 Protocol for differential analysis of Trim71-associated protein complexes in mouse embryonic stem cells by mass spectrometry using Perseus. STAR protocols 0 39116200
2023 Reactivation of the progenitor gene Trim71 enhances the mitotic and hair cell-forming potential of cochlear supporting cells. bioRxiv : the preprint server for biology 0 36711735
2018 Bioinformat-Eggs: An Educational Primer for Use with "LIN-41 and OMA Ribonucleoprotein Complexes Mediate a Translational Repression-to-Activation Switch Controlling Oocyte Meiotic Maturation and the Oocyte-to-Embryo Transition in Caenorhabditis elegans". Genetics 0 29967060

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