Affinage

NXF1

Nuclear RNA export factor 1 · UniProt Q9UBU9

Length
619 aa
Mass
70.2 kDa
Annotated
2026-06-10
89 papers in source corpus 48 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NXF1 (TAP/Mex67) is the principal nuclear export receptor for the bulk of polyadenylated mRNA, operating as a heterodimer with p15/NXT1/Mtr2 to ferry mRNP cargo through the nuclear pore complex (PMID:11073998, PMID:11780633, PMID:11780634). Its modular architecture — an RNP-type RNA-binding domain, leucine-rich repeats, an NTF2-like domain that heterodimerizes with p15, and a C-terminal UBA-like domain — couples RNA recognition to translocation: the UBA four-helix bundle and the p15-bound NTF2-like scaffold each provide synergistic FG-nucleoporin binding sites that drive directional export (PMID:11073998, PMID:11875519, PMID:12101235). Structural work shows NXF1-NXT1 forms a domain-swapped, two-fold symmetric RNA-binding platform that recognizes structured export elements such as the CTE, with the NTF2-like domain itself extending the RNA-binding surface (PMID:25628361, PMID:25618852). NXF1 is autoinhibited until the TREX subunits Aly and Thoc5 contact it and drive an open conformation that licenses mRNA binding (PMID:22893130), and it is loaded onto cargo by a diverse set of adaptors including U2AF35, SR proteins (most potently SRSF3 and SRSF7), RBM15/RBM15B, and the neuron-specific HuD, several of which couple splicing and polyadenylation to export-factor recruitment (PMID:11724776, PMID:26944680, PMID:17001072, PMID:19586903, PMID:15358174, PMID:41110461). Cargo selection is sequence-biased: NXF1 preferentially exports single-exon or A/U-rich, long-exon transcripts and cooperates with the cleavage factor CFI-68 to export long 3'-UTR isoforms, also influencing alternative polyadenylation and Pol II dynamics at gene 3' ends (PMID:30819645, PMID:32504555). Recruitment to active genes is reinforced cotranscriptionally through the UBA domain, which binds polyubiquitin and the ubiquitylated THO component Hpr1, with an FXFG/Hpr1 binding switch on the UBA controlling the handover between transcription and translocation (PMID:17056718, PMID:17475778, PMID:19401465). At the cytoplasmic face of the NPC, NXF1 mediates terminal mRNP release in a Dbp5 helicase-dependent manner (PMID:31375530, PMID:33002012). Beyond mRNA, the Mex67-Mtr2 dimer exports 60S ribosomal subunits and primary tRNAs through dedicated surfaces of its NTF2-like scaffold (PMID:17434126, PMID:22956913, PMID:29212662). A natural Nxf1 allele acts as a quantitative genetic modifier of retrotransposon-induced splicing defects, an activity recreated by a single UBA-region substitution, linking the export receptor to pre-mRNA processing fidelity (PMID:14517553, PMID:25835743). NXF1 is also exploited by numerous viruses — including HSV-1 ICP27, EBV EB2, MLV, HBV, influenza, and Ebola — as the export route for their transcripts (PMID:15767397, PMID:19019956, PMID:19369354, PMID:19793817, PMID:24478440, PMID:25360769, PMID:39384042, PMID:36040180).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2000 High

    Established the domain logic of NXF1 — how a single receptor can both grip RNA and engage the pore — by dissecting its modular architecture into RNA-binding, LRR, p15-dimerizing NTF2-like, and nucleoporin-binding UBA modules.

    Evidence Domain dissection with in vitro binding and functional export assays

    PMID:11073998

    Open questions at the time
    • Did not resolve the structural basis of FG-nucleoporin contact
    • Adaptor-mediated cargo loading not yet mapped
  2. 2001 High

    Demonstrated genetically that NXF1/p15 is the bulk mRNA export pathway in metazoa, distinguishing it from paralogs, by showing depletion blocks export of spliced and intronless poly(A)+ RNA while NXF2-4 loss does not.

    Evidence RNAi depletion in Drosophila S2 cells with poly(A)+ FISH

    PMID:11780633 PMID:11780634

    Open questions at the time
    • Did not identify which adaptors load bulk mRNA onto NXF1
    • Substrate sequence preferences unresolved
  3. 2001 Medium

    Identified the first direct splicing-to-export adaptor link by showing U2AF35 binds a distinct TAP region and helps add TAP to spliced mRNPs.

    Evidence Yeast two-hybrid, in vitro binding, co-IP, Xenopus oocyte export assays

    PMID:11724776

    Open questions at the time
    • Single lab
    • Relative contribution versus REF/ALY adaptors not quantified
  4. 2002 High

    Defined the structural and functional basis of NPC engagement, showing the UBA four-helix bundle and the p15-NTF2-like scaffold provide two synergistic FG-nucleoporin sites sufficient for directional export.

    Evidence NMR structure, mutagenesis (F617A), Xenopus oocyte export assays

    PMID:11875519 PMID:12101235

    Open questions at the time
    • Did not identify which specific nucleoporins are physiological docking sites in vivo
  5. 2003 High

    Linked NXF1 to pre-mRNA processing fidelity in vivo by identifying a natural Nxf1 allele that suppresses retrovirus-insertion-induced splicing defects.

    Evidence Positional complementation cloning and congenic mouse genetics with RNA analysis

    PMID:14517553

    Open questions at the time
    • Causal residue not yet pinpointed
    • Mechanism linking export receptor to splicing outcome unresolved
  6. 2004 High

    Identified RanBP2/Nup358 as a specific physiological NPC docking site for NXF1-p15, distinguishing it from Nup214 by reciprocal depletion phenotypes.

    Evidence RNAi in Drosophila cells with immunofluorescence and FISH

    PMID:14729961

    Open questions at the time
    • Does not establish order of nucleoporin contacts during translocation
  7. 2006 High

    Revealed cotranscriptional recruitment via the UBA domain, which binds polyubiquitin and protects the ubiquitylated THO component Hpr1, tying export-machinery loading to transcription.

    Evidence ChIP, in vitro binding, ubiquitin interaction assays, co-IP in yeast

    PMID:17056718

    Open questions at the time
    • Structural basis of the ubiquitin/Hpr1 selectivity not yet resolved at this stage
  8. 2006 Medium

    Expanded the adaptor repertoire to cell-type-specific and element-specific routes by identifying neuronal HuD and RBM15 as direct NXF1 adaptors for AU-rich and RTE-containing mRNAs.

    Evidence In vitro binding, ternary complex assays, yeast two-hybrid, tethering and siRNA export readouts

    PMID:15358174 PMID:17001072

    Open questions at the time
    • Single-lab interactions
    • Physiological mRNA targets in neurons not transcriptome-mapped
  9. 2007 High

    Resolved the UBA domain as a molecular switch and showed FXFG-nucleoporin and Hpr1 bind overlapping UBA sites, providing a structural logic for handing cargo from transcription to translocation.

    Evidence NMR structures of UBA alone and with FXFG peptide, mutagenesis, FRET, ChIP

    PMID:17475778 PMID:19401465

    Open questions at the time
    • Temporal sequence of switching in vivo not directly visualized
  10. 2007 High

    Established a separate Mex67-Mtr2 function in 60S ribosomal subunit export via a loop-extended electrostatic NTF2-like surface that also contacts the Nup84 complex, defining a distinct cargo channel.

    Evidence In vitro reconstitution, mutagenesis, yeast genetics, crosslinking, competition assays

    PMID:17434126 PMID:18046452 PMID:22956913

    Open questions at the time
    • This surface is absent in human TAP-p15, so the human ribosome-export route is unaddressed
  11. 2010 High

    Explained the mechanism of cargo handover, showing arginine methylation lowers REF/ALY RNA affinity to allow TAP to strip RNA from the adaptor during loading.

    Evidence MS methylation mapping, in vitro and in vivo RNA-binding assays, mutagenesis

    PMID:20129943

    Open questions at the time
    • Methyltransferase responsible and regulation of the modification not defined here
  12. 2011 High

    Defined how NXF1 itself gets into the nucleus, mapping two cooperative NLS epitopes engaged by redundant karyopherins required for export function.

    Evidence Biochemical karyopherin binding, mutagenesis, localization and export assays

    PMID:21965294

    Open questions at the time
    • Relative in vivo flux through each karyopherin pathway not quantified
  13. 2011 Medium

    Identified a nuclear quality-control brake, showing Tpr selectively restricts export of intron-retaining mRNAs through the NXF1 pathway without affecting CRM1 cargo.

    Evidence RNAi knockdown with pathway-specific CTE versus RRE reporters

    PMID:21613532

    Open questions at the time
    • Single lab
    • Direct Tpr-NXF1 contact and discrimination mechanism unresolved
  14. 2012 High

    Resolved how RNA binding is gated, showing NXF1 is autoinhibited until Aly and Thoc5 drive it open to expose its RNA-binding domain.

    Evidence Co-IP, RNA-binding assays, dual RNAi with export readout

    PMID:22893130

    Open questions at the time
    • Structure of the open versus closed state in human NXF1 not solved here
  15. 2015 High

    Provided high-resolution structural frameworks for the RNA-binding platform, showing the domain-swapped NXF1-NXT1 dimer and the NTF2-like contribution to RNA binding.

    Evidence X-ray crystallography of human NXF1-NXT1 and yeast Mex67-Mtr2, SAXS, RNA-binding assays

    PMID:25618852 PMID:25628361

    Open questions at the time
    • Full-length receptor with mobile RRM/UBA domains on cargo not captured
  16. 2015 High

    Pinpointed the genetic modifier to a single UBA-region residue (E610G), causally connecting NXF1 to alternative-splicing outcomes at retrotransposon insertions.

    Evidence CRISPR/Cas9 editing in co-isogenic mice with transcriptome-wide splicing arrays

    PMID:25835743

    Open questions at the time
    • Biochemical effect of E610G on UBA-ubiquitin/nucleoporin binding not directly measured
  17. 2015 High

    Identified TREX-2 as an mRNP concentrator at the pore entrance, showing Sac3 phenylalanine motifs engage the Mex67 NTF2-like domain like FG-nucleoporins.

    Evidence Crystal structure, in vitro reconstitution, yeast genetics and export assays

    PMID:26051714

    Open questions at the time
    • How TREX-2 hands cargo to FG-nucleoporins not directly observed
  18. 2016 High

    Defined SR proteins as principal, sequence-specific export adaptors, with SRSF3/SRSF7 co-binding mRNA adjacent to NXF1 and coupling alternative splicing and polyadenylation to export.

    Evidence iCLIP co-binding analysis, siRNA knockdown, RNA-seq

    PMID:26944680

    Open questions at the time
    • Direct SRSF-NXF1 contact interface not structurally defined
  19. 2016 Medium

    Revealed an autoregulatory neuronal isoform, sNxf1, an intron-retaining CTE-exported variant that heterodimerizes with full-length NXF1 and can substitute for NXT1 to promote translation of CTE mRNAs.

    Evidence Brain immunofluorescence, fractionation, co-IP, reporter and polyribosome assays

    PMID:27708137

    Open questions at the time
    • Single lab
    • Physiological neuronal mRNA targets and in vivo function not established
  20. 2017 High

    Extended Mex67-Mtr2 function to tRNA export, showing it cofunctions with Los1 and can substitute for it in primary tRNA nuclear export.

    Evidence Genetic inactivation, tRNA FISH, in vivo co-IP, overexpression rescue in yeast

    PMID:29212662

    Open questions at the time
    • Whether human TAP-p15 exports tRNAs is not addressed
  21. 2019 High

    Localized the essential export step spatially and temporally, showing Mex67/NXF1 acts at the NPC and is required for terminal mRNP release on the cytoplasmic face in a Dbp5-dependent manner rather than for initial docking.

    Evidence FRAP/single-molecule tracking, nucleoporin-fusion rescue, superresolution microscopy, FLIM-FRET, proximity ligation

    PMID:31375530 PMID:31753862 PMID:33002012

    Open questions at the time
    • Molecular trigger that times Dbp5-driven release relative to translocation not fully resolved
  22. 2019 High

    Connected NXF1 to 3'-end processing and Pol II dynamics, showing it promotes distal polyA site usage and cooperates with CFI-68 to export long 3'-UTR transcripts.

    Evidence siRNA knockdown, RNA-seq, Pol II ChIP-seq, 3'-end sequencing, co-IP

    PMID:30819645

    Open questions at the time
    • Direct mechanism by which export coupling feeds back on Pol II termination unresolved
  23. 2020 High

    Defined cargo selection rules, showing NXF1 preferentially exports single/few-exon, long, A/U-rich transcripts whereas TREX favors spliced G/C-rich mRNAs, with short sufficient sequence elements identified.

    Evidence Quantitative RNA fractionation after depletion and massively parallel reporter assays

    PMID:32504555

    Open questions at the time
    • Adaptor(s) reading the A/U-rich determinants not fully assigned
  24. 2025 Medium

    Placed NXF1 directly in alternative-splicing-driven oncogenic control, showing it interferes with SRSF3 binding to SP4 pre-mRNA to favor the non-oncogenic isoform and suppress carcinoma proliferation.

    Evidence Mouse tumor models, co-IP and splicing assays, in vitro functional assays

    PMID:40792019

    Open questions at the time
    • Single lab
    • Generality of splicing regulation beyond SP4 not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NXF1 integrates its diverse roles — bulk export, isoform-specific selection, ribosome/tRNA export, cotranscriptional ubiquitin sensing, and reported signaling roles — into a unified regulatory program remains open.
  • The IRF5/TLR7 and CDK12-stabilization roles rest on single low-confidence studies
  • No structure of full-length receptor engaging cargo at the NPC
  • Adaptor hierarchy across cell types not quantitatively resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0060090 molecular adaptor activity 4 GO:0005215 transporter activity 3 GO:0140104 molecular carrier activity 2
Localization
GO:0005635 nuclear envelope 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-9609507 Protein localization 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
ALYREFDDX19/DBP5NXT1RBM15SRSF3SRSF7THOC5U2AF1
Complex memberships
NXF1-NXT1/p15 (Mex67-Mtr2) heterodimerTREXTREX-2

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 TAP/NXF1 has a modular architecture comprising an RNP-type RNA-binding domain, four leucine-rich repeats (LRR), an NTF2-like domain that mediates heterodimerization with p15/NXT1, and a UBA-like domain that mediates interaction with FG-nucleoporins at the nuclear pore complex. Domain analysis, in vitro binding assays, functional export assays Molecular and cellular biology High 11073998
2002 The C-terminal UBA-like domain of NXF1/TAP has a four-helix bundle structure and mediates FG-nucleoporin binding; mutation F617A suppresses this interaction. The NTF2-like scaffold (heterodimerized with p15) provides a second nucleoporin-binding site, and both sites act synergistically; two copies of either domain alone are sufficient for directional mRNA export independent of p15. NMR structure determination; mutagenesis; Xenopus oocyte export assays Nature structural biology / Molecular and cellular biology High 11875519 12101235
2001 Drosophila NXF1 (small bristles/sbr) and p15 are essential for nuclear export of the bulk of polyadenylated mRNAs (heat-shock and non-heat-shock, spliced and intronless) in Drosophila cells; depletion of NXF2–NXF4 has no equivalent phenotype. RNAi depletion in Drosophila S2 cells; fluorescence in situ hybridization (FISH) for poly(A)+ RNA RNA High 11780633 11780634
2004 The nucleoporin RanBP2/Nup358 (cytoplasmic filaments of the NPC) provides a major binding site for NXF1-p15 dimers; depletion of RanBP2 causes NXF1 to redistribute to the cytoplasm and blocks mRNA export, whereas depletion of CAN/Nup214 blocks export without displacing NXF1, demonstrating specificity of the RanBP2–NXF1 interaction. RNAi depletion in Drosophila cells; immunofluorescence; FISH Molecular and cellular biology High 14729961
2001 NXF1/TAP is recruited to spliced mRNPs via a direct interaction with U2AF35 (small subunit of splicing factor U2AF); a distinct region of TAP mediates this interaction, which is evolutionarily conserved across metazoa and facilitates TAP's addition to mRNA substrates. Yeast two-hybrid; in vitro binding with recombinant proteins; co-immunoprecipitation; Xenopus oocyte export assays The Journal of biological chemistry Medium 11724776
2006 The UBA domain of yeast Mex67 (NXF1 ortholog) directly interacts with polyubiquitin chains and with Hpr1 (a THO/TREX component that is regulated by ubiquitylation in a transcription-dependent manner), transiently protecting Hpr1 from proteasomal degradation and thereby recruiting the mRNA export machinery to transcribing genes. Chromatin immunoprecipitation; in vitro binding; mutagenesis; co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 17056718
2007 The yeast Mex67-Mtr2 heterodimer mediates nuclear export of 60S ribosomal subunits via a distinct loop-extended electrostatic surface on its NTF2-like scaffold that binds pre-60S particles and 5S rRNA; this surface is absent from human TAP-p15 and is separate from the mRNA export interface. Biochemical interaction assays; mutagenesis; yeast genetics; ribosome export assays Molecular cell High 17434126 22956913
2007 Mex67-Mtr2 interacts with the Nup84 complex (a structural NPC module lacking FG repeats) through the same loop surface that recruits pre-60S particles; Nup85 is the direct contact subunit. This interaction is essential for mRNA export. Chemical crosslinking; in vitro competition assays; yeast genetic suppressor analysis The EMBO journal Medium 18046452
2012 NXF1 uses an intramolecular interaction to autoinhibit its RNA-binding activity. The TREX subunits Aly and Thoc5 contact NXF1 and drive it into an open conformation that exposes its RNA-binding domain, licensing mRNA binding. Combined knockdown of Aly and Thoc5 markedly reduces NXF1-mRNA association and causes severe mRNA export block. Co-immunoprecipitation; RNA-binding assays; RNAi knockdown with mRNA export readout Nature communications High 22893130
2016 SR proteins (SRSF1-7) act as NXF1 export adaptors that bind mRNA at sites adjacent to NXF1-binding sites (co-binding). SRSF3 and SRSF7 each promote NXF1 recruitment to mRNA and couple alternative splicing and polyadenylation to NXF1-mediated export; SRSF3 is the most potent adaptor and confers sequence specificity to NXF1 binding in last exons. iCLIP (individual-nucleotide-resolution UV cross-linking and immunoprecipitation); siRNA knockdown; RNAseq Genes & development High 26944680
2015 Crystal structure (3.4 Å) of human NXF1 (RRM-LRR-NTF2-like domains) in complex with NXT1 reveals a domain-swapped dimer in which linkers between LRR and NTF2-like domains interact with NXT1, forming a 2-fold symmetric RNA-binding platform that facilitates recognition of the CTE RNA stem-loop and promotes its nuclear export. X-ray crystallography; biochemical binding assays; cell-based export assays Nucleic acids research High 25628361
2006 NXF1/TAP directly interacts with the neuronal RNA-binding protein HuD (but not the ubiquitous HuR); HuD forms a ternary complex with TAP and RNA, suggesting HuD acts as a neuron-specific adaptor for NXF1-mediated export of AU-rich element-containing mRNAs. In vitro binding with recombinant proteins; ternary complex formation assay Biochemical and biophysical research communications Medium 15358174
2006 RBM15 (OTT1) directly binds the RNA transport element RTE and interacts directly with NXF1 via its C-terminal region, functioning as a novel export adaptor that links RTE-containing mRNAs to the NXF1 export pathway. In vitro RNA binding; yeast two-hybrid; co-immunoprecipitation; tethering assay; siRNA knockdown with export readout The Journal of biological chemistry Medium 17001072
2009 RBM15B/OTT3, like its paralog RBM15, directly interacts with NXF1 and Aly/REF via its C-terminal region, associates with the splicing factor compartment and nuclear envelope, and has post-transcriptional regulatory activity, functioning as an NXF1 cofactor. Co-immunoprecipitation; subcellular localization; mutational analysis The Journal of biological chemistry Medium 19586903
2010 Arginine methylation of REF/ALY reduces its RNA-binding affinity without affecting its TAP/NXF1 interaction; this reduced RNA binding is required for efficient displacement of RNA from REF by TAP during the handover of mRNA to NXF1 for export. Mass spectrometry methylation mapping; in vitro binding assays; in vivo RNA-binding assays; mutagenesis Nucleic acids research High 20129943
2011 The nuclear protein Tpr restricts nuclear export of intron-retaining mRNAs that traffic through the NXF1/Nxt1 pathway; Tpr knockdown increases export and translation from a CTE-containing retained-intron reporter but has no effect on CRM1-pathway (Rev/RRE) export or completely spliced mRNA export. RNAi knockdown; reporter mRNA export/expression assays (CTE vs. RRE reporters); pathway-specific readouts RNA Medium 21613532
2011 NXF1 is imported into the nucleus via redundant karyopherin pathways (importin β, karyopherin β2/transportin, importin 4, importin 11, importin α). Two NLS epitopes in NXF1's N-terminal tail (an N-terminal basic segment and an R-X2-5-P-Y motif) provide the majority of binding energy; mutation of both NLS epitopes mislocalizes NXF1 to the cytoplasm and impairs mRNA export function. Biochemical binding assays; mutagenesis; cellular localization studies; functional export assays Molecular biology of the cell High 21965294
2019 In yeast, Mex67 localizes constitutively to the NPC independently of mRNA, occupying FG-repeat binding sites; its essential export function is spatially restricted to the NPC, as a Mex67-Nup116 fusion that anchors Mex67 at the NPC rescues mex67Δ. Mex67 has little interaction with mRNA in the nucleus and receives export substrates at the NPC channel. Quantitative live-cell fluorescence microscopy (FRAP, single-molecule tracking); genetic rescue with nucleoporin fusion The Journal of cell biology High 31753862
2019 NXF1 is required for mRNA release on the cytoplasmic side of the NPC but not for initial mRNP docking to the NPC. NXF1 occupies cytoplasmic-side positions within the NPC (superresolution microscopy), and its NPC localization is RNA-independent. Dbp5 helicase activity is required for mRNP release at the cytoplasmic face, a mechanism conserved between yeast and humans. Live-cell mRNA export block assays; superresolution microscopy; FLIM-FRET within single NPCs The Journal of cell biology High 31375530
2019 NXF1 downregulation causes RNA Pol II accumulation at the 3' end of genes; NXF1 promotes usage of distal polyadenylation sites, generating long 3' UTR isoforms. NXF1 cooperates with the cleavage factor CFI-68 to facilitate nuclear export of long 3' UTR transcripts containing UGUA motifs. siRNA knockdown; RNA-seq; Pol II ChIP-seq; 3' end sequencing (APA profiling); co-immunoprecipitation Molecular cell High 30819645
2020 NXF1 is preferentially required for nuclear export of single-exon or few-exon transcripts with long exons or high A/U content, while TREX complex components preferentially facilitate export of spliced G/C-rich transcripts. Short sequence elements sufficient to confer NXF1-dependence were identified by massively parallel reporter assays. Quantitative RNA fractionation after siRNA depletion; massively parallel reporter assays; transcriptome-wide RNA localization profiling Molecular cell High 32504555
2017 Mex67-Mtr2 (TAP-p15) cofunctions with Los1 (Exportin-t) in primary tRNA nuclear export in yeast; inactivation of Mex67 or Mtr2 causes nuclear accumulation of end-matured unspliced tRNAs, and Mex67 co-immunoprecipitates with tRNAs in vivo. Mex67-Mtr2 overexpression can substitute for Los1. Genetic inactivation; FISH for tRNA localization; in vivo co-immunoprecipitation; overexpression rescue Genes & development High 29212662
2007 The UBA domain of Mex67 has a classical three-helix UBA fold plus a fourth helix (H4) that acts as a molecular switch: H4 coordinates interaction with ubiquitin-bound Hpr1, selects for polyubiquitin, and prevents binding to non-specific substrates. Deletion or mutation of H4 strengthens ubiquitin binding but decreases Hpr1 affinity and reduces cotranscriptional Mex67 recruitment and mRNA export. NMR structure; mutagenesis; fluorescence-based binding assays; chromatin immunoprecipitation Molecular biology of the cell High 17475778
2009 NMR solution structure of the Mex67 UBA domain complexed with an FXFG nucleoporin peptide shows that Hpr1 and FXFG nucleoporins bind overlapping sites on UBA-Mex67; FXFG binding prevents UBA-Mex67 from subsequently binding ubiquitin, whereas Hpr1 binding allows polyubiquitin interaction. NMR structure; FRET-based binding assays; NMR titration The Journal of biological chemistry High 19401465
2015 Crystal structure (3.3 Å) of yeast Mex67(ΔUBA):Mtr2 shows the LRR domain has a defined spatial relationship to the NTF2-like region; the NTF2-like domain of Mex67:Mtr2 contributes directly to RNA binding, extending the mRNA-binding surface. RRM and UBA domains are more mobile. X-ray crystallography; SAXS; RNA-binding assays Nucleic acids research High 25618852
2015 The TREX-2 complex (Sac3-Thp1-Sem1-Sus1-Cdc31) interacts with Mex67:Mtr2 through the Sac3 N-terminal region via phenylalanine-containing motifs that bind the Mex67 NTF2-like domain similarly to FG-nucleoporins; deletion of Sac3N causes mRNA export defects, placing TREX-2 as a concentrator of mRNPs at the NPC entrance. Crystal structure; in vitro reconstitution; yeast genetic growth and export assays Structure High 26051714
2003 A natural allele of mouse Nxf1 (Nxf1^CAST from Mus musculus castaneus) suppresses intronic endogenous retrovirus insertion-induced mutations (Pitpn^vb, Eya1^BOR) by increasing correctly spliced mRNA and decreasing aberrant alternatively processed RNA, linking the mRNA export receptor to pre-mRNA processing fidelity. Positional complementation cloning; congenic mouse genetics; RNA analysis Nature genetics High 14517553
2009 A single amino acid substitution E610G in Nxf1 (within the UBA domain region) is sufficient to recreate the quantitative genetic modifier activity of the Nxf1^CAST allele for IAP retrotransposon insertion-induced alternative splicing defects, as demonstrated by CRISPR/Cas9-mediated genome editing. CRISPR/Cas9 genome editing; genome-wide splicing-sensitive microarrays; gene-focused splicing assays PLoS genetics High 25835743
2009 Drosophila NXF1/sbr loss-of-function causes disruption of the meiotic spindle in females and formation of tripolar spindles during the first meiotic division; the sbr^5 lethal allele deletes 492 nucleotides removing residues within the NTF2-like domain. Genetic analysis of mutant alleles; cytological analysis of meiotic spindles; sequencing of sbr allele Chromosome research Medium 19779841
2016 An NXF1 isoform (short NXF1, sNxf1), translated from an intron-10-retaining mRNA exported via a CTE element, is highly expressed in hippocampal and neocortical neurons. sNxf1 localizes to RNA granules in neurites, forms heterodimers with full-length NXF1, and can replace NXT1 to enhance expression of CTE-containing mRNA and promote its association with polyribosomes. Immunofluorescence in rodent brain; subcellular fractionation; co-immunoprecipitation; reporter expression/polyribosome profiling assays Molecular biology of the cell Medium 27708137
2007 NXF1 TAP/NXF1 directly interacts with the HSV-1 protein ICP27 via the C-terminus of ICP27 (with N-terminal contribution); this interaction is required for ICP27's cytoplasmic export and for efficient nuclear export of HSV-1 viral transcripts. Aly/REF is not required for ICP27 export despite being recruited to viral transcription sites. Co-immunoprecipitation; in vitro binding; siRNA knockdown; in situ hybridization Journal of virology / Journal of virology High 15767397 19019956 19369354
2009 The Epstein-Barr virus protein EB2 contains a CRM1-independent nuclear export signal (NES, aa 61–146) composed of arginine-rich domains that interact directly with TAP/NXF1 and mediate mRNA export; the NES fused to a heterologous protein can export MS2-tethered mRNA. Co-immunoprecipitation; tethering export assay; mutagenesis Journal of virology Medium 19793817
2014 The gammaretrovirus MLV (murine leukemia virus) contains a cis-acting cytoplasmic accumulation element (CAE) in the pol gene that binds NXF1 directly; NXF1 depletion abolishes CAE function and causes nuclear retention or degradation of both spliced and unspliced MLV RNA transcripts. siRNA knockdown; RNA immunoprecipitation; FISH; co-immunoprecipitation Journal of virology Medium 24478440
2014 HBV core protein (HBc) associates with TREX components and NXF1-p15 by co-immunoprecipitation, and interference with NXF1-p15 function causes nuclear accumulation of HBc. HBV pregenomic RNA (pgRNA) export to the cytoplasm is reduced by NXF1-p15 siRNA, demonstrating that both HBc and pgRNA use the NXF1-p15 pathway. Co-immunoprecipitation; siRNA knockdown; RT-qPCR; Northern blot PloS one Medium 25360769
2019 Mip6 (a four-RRM RNA-binding protein in yeast) directly interacts with the UBA domain of Mex67 through a loop containing tryptophan 442; Mip6 shuttles between nucleus and cytoplasm in a Mex67-dependent manner and its deletion affects export and expression levels of Msn2/4-regulated stress-response mRNAs. Structural characterization; FRET-based binding assays; PAR-CLIP; genetic knockout analysis EMBO reports Medium 31680439
2017 NXF1 interacts with IRF5 and is identified as a regulator of TLR7-dependent IRF5 transcriptional signaling; TLR7 stimulation enhances IRF5-NXF1 protein complex formation, and gain/loss-of-function experiments confirm NXF1 selectively regulates TLR7-driven IRF5 transcriptional activity. Affinity purification-mass spectrometry; RNAi screen; co-immunoprecipitation; gain/loss-of-function reporter assays Scientific reports Low 28578407
2022 NXF1 is required for export of Ebola virus (EBOV) mRNAs from cytoplasmic viral inclusion bodies (IBs). RNA binding by both NXF1 and EBOV NP is necessary for NXF1 export from IBs; NP and NXF1 interact at two separate sites (one involving the NP RNA-binding cleft), these interactions are RNA-independent. NXF1 is also required for mRNA expression from other IB-replicating viruses (Lloviu, Junín). siRNA knockdown; complementation assays; immunofluorescence; domain-mapping co-immunoprecipitation Journal of virology Medium 36040180
2020 The DEAD-box helicase Dbp5 associates in close proximity with Mex67 and Nab2 in a cellular complex at the cytoplasmic face of the NPC; anchoring Dbp5 to Nup159 is sufficient for cell viability, supporting a model where Dbp5 remodels mRNPs by locally releasing Mex67 and Nab2 at the NPC. Proximity ligation assay; genetic NUP fusion rescue experiments; co-immunoprecipitation PLoS genetics Medium 33002012
2007 In vivo BiFC analysis shows Y14 and NXF1 form a complex that accumulates preferentially within and around nuclear speckles (SC35 domains); about half of these complexes are immobile in vivo and are depleted by ATP administration, suggesting an ATP-dependent nuclear retention mechanism for a fraction of mRNAs. Bimolecular fluorescence complementation (BiFC); FRAP; FLIP; co-immunoprecipitation; ATP depletion assay The Journal of cell biology Medium 16431928
2024 NS1-BP competes with viral NS1 protein for NXF1 binding during influenza A infection, allowing NXF1 recruitment to influenza M segment mRNAs after splicing. NXF1 then binds GANP (a TREX-2 component), and the NS1/NS1-BP–GANP–NXF1 complex dissociates at the NPC to allow M1 and M2 mRNA export. Co-immunoprecipitation; biochemical competition assays; subcellular mRNA localization; siRNA knockdown The Journal of biological chemistry Medium 39384042
2025 NXF1 interacts with CDK12 kinase; NXF1 does not phosphorylate CDK12, but rather stabilizes CDK12 protein. CDK12 kinase activity recruits the EJC and THO complexes into a CDK12-NXF1 axis, linking mRNA transcription and transport. Co-immunoprecipitation; protein stability assays; kinase assays; complex interaction studies Biochemical and biophysical research communications Low 39270556
2025 NXF1 inhibits ECa cell proliferation and invasion; mechanistically, NXF1 interferes with SRSF3 binding to exon 3 of SP4 pre-mRNA, promoting the short (non-oncogenic) SP4 isoform over the long (oncogenic) isoform through an SRSF3-mediated alternative splicing mechanism. Mouse tumor models; molecular biology assays (co-IP, splicing assays); in vitro functional assays iScience Medium 40792019
2025 The HuD linker region mediates direct interaction with TAP/NXF1; this TAP/NXF1-binding domain is functionally separable from cytoplasmic localization and is required for stimulation of cap-dependent translation and neurite outgrowth, establishing a mechanistic link between the RNA export factor NXF1 and ELAV-mediated translational control. Deletion mutant analysis; co-immunoprecipitation; translation assays; neurite outgrowth assays Genes to cells Medium 41110461

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export. Genes & development 241 26944680
2000 TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture. Molecular and cellular biology 173 11073998
2012 TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export. Nature communications 168 22893130
2001 NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila. RNA (New York, N.Y.) 144 11780633
2007 Nuclear export of ribosomal 60S subunits by the general mRNA export receptor Mex67-Mtr2. Molecular cell 130 17434126
2006 Ubiquitin-associated domain of Mex67 synchronizes recruitment of the mRNA export machinery with transcription. Proceedings of the National Academy of Sciences of the United States of America 115 17056718
2020 Gene Architecture and Sequence Composition Underpin Selective Dependency of Nuclear Export of Long RNAs on NXF1 and the TREX Complex. Molecular cell 114 32504555
2004 RanBP2/Nup358 provides a major binding site for NXF1-p15 dimers at the nuclear pore complex and functions in nuclear mRNA export. Molecular and cellular biology 90 14729961
2002 Nuclear export of mRNA by TAP/NXF1 requires two nucleoporin-binding sites but not p15. Molecular and cellular biology 86 12101235
2005 ICP27 recruits Aly/REF but not TAP/NXF1 to herpes simplex virus type 1 transcription sites although TAP/NXF1 is required for ICP27 export. Journal of virology 85 15767397
2010 Individual influenza A virus mRNAs show differential dependence on cellular NXF1/TAP for their nuclear export. The Journal of general virology 84 20071484
2011 The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA (New York, N.Y.) 69 21613532
2007 Fragile X mental retardation protein FMRP and the RNA export factor NXF2 associate with and destabilize Nxf1 mRNA in neuronal cells. Proceedings of the National Academy of Sciences of the United States of America 66 17548835
2002 Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1. Nature structural biology 63 11875519
2012 Role of Mex67-Mtr2 in the nuclear export of 40S pre-ribosomes. PLoS genetics 60 22956913
2006 In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential localization within and around SC35 domains. The Journal of cell biology 59 16431928
2001 U2AF participates in the binding of TAP (NXF1) to mRNA. The Journal of biological chemistry 58 11724776
2010 Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1. Nucleic acids research 55 20129943
2006 RNA-binding motif protein 15 binds to the RNA transport element RTE and provides a direct link to the NXF1 export pathway. The Journal of biological chemistry 53 17001072
2015 The principal mRNA nuclear export factor NXF1:NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA. Nucleic acids research 50 25628361
2008 Efficient nuclear export of herpes simplex virus 1 transcripts requires both RNA binding by ICP27 and ICP27 interaction with TAP/NXF1. Journal of virology 50 19019956
2009 The cellular RNA export receptor TAP/NXF1 is required for ICP27-mediated export of herpes simplex virus 1 RNA, but the TREX complex adaptor protein Aly/REF appears to be dispensable. Journal of virology 49 19369354
2009 The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the nuclear export receptor NXF1. The Journal of biological chemistry 49 19586903
2001 Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development. RNA (New York, N.Y.) 49 11780634
2007 A versatile interaction platform on the Mex67-Mtr2 receptor creates an overlap between mRNA and ribosome export. The EMBO journal 46 18046452
2019 The mRNA Export Receptor NXF1 Coordinates Transcriptional Dynamics, Alternative Polyadenylation, and mRNA Export. Molecular cell 45 30819645
2019 The RNA export factor Mex67 functions as a mobile nucleoporin. The Journal of cell biology 40 31753862
2011 Perturbation of U2AF65/NXF1-mediated RNA nuclear export enhances RNA toxicity in polyQ diseases. Human molecular genetics 39 21725067
2024 HnRNPA2B1 ISGylation Regulates m6A-Tagged mRNA Selective Export via ALYREF/NXF1 Complex to Foster Breast Cancer Development. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 38 38626369
2013 The nuclear mRNA export receptor Mex67-Mtr2 of Trypanosoma brucei contains a unique and essential zinc finger motif. Molecular microbiology 37 23560737
2009 Epstein-Barr virus protein EB2 contains an N-terminal transferable nuclear export signal that promotes nucleocytoplasmic export by directly binding TAP/NXF1. Journal of virology 37 19793817
2017 Sharing the load: Mex67-Mtr2 cofunctions with Los1 in primary tRNA nuclear export. Genes & development 35 29212662
2019 Imaging within single NPCs reveals NXF1's role in mRNA export on the cytoplasmic side of the pore. The Journal of cell biology 34 31375530
2007 XIST RNA exhibits nuclear retention and exhibits reduced association with the export factor TAP/NXF1. Chromosoma 33 17333237
2014 Nuclear export of human hepatitis B virus core protein and pregenomic RNA depends on the cellular NXF1-p15 machinery. PloS one 32 25360769
2009 Varicella-zoster virus IE4 protein interacts with SR proteins and exports mRNAs through the TAP/NXF1 pathway. PloS one 32 19924249
2003 A natural allele of Nxf1 suppresses retrovirus insertional mutations. Nature genetics 32 14517553
2016 An NXF1 mRNA with a retained intron is expressed in hippocampal and neocortical neurons and is translated into a protein that functions as an Nxf1 cofactor. Molecular biology of the cell 31 27708137
2014 Murine leukemia virus uses NXF1 for nuclear export of spliced and unspliced viral transcripts. Journal of virology 31 24478440
2010 Export of adenoviral late mRNA from the nucleus requires the Nxf1/Tap export receptor. Journal of virology 29 21123381
2014 HIV-1 Rev protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment. Nucleic acids research 28 24753416
2015 Structural Characterization of the Chaetomium thermophilum TREX-2 Complex and its Interaction with the mRNA Nuclear Export Factor Mex67:Mtr2. Structure (London, England : 1993) 27 26051714
2020 NXF1 and CRM1 nuclear export pathways orchestrate nuclear export, translation and packaging of murine leukaemia retrovirus unspliced RNA. RNA biology 26 31918596
2016 ORC interacts with THSC/TREX-2 and its subunits promote Nxf1 association with mRNP and mRNA export in Drosophila. Nucleic acids research 26 27016737
2004 TAP/NXF1, the primary mRNA export receptor, specifically interacts with a neuronal RNA-binding protein HuD. Biochemical and biophysical research communications 26 15358174
2002 An element in the 3' untranslated region of human LINE-1 retrotransposon mRNA binds NXF1(TAP) and can function as a nuclear export element. RNA (New York, N.Y.) 24 12003494
2015 Domain organization within the nuclear export factor Mex67:Mtr2 generates an extended mRNA binding surface. Nucleic acids research 23 25618852
2007 Coordination of Hpr1 and ubiquitin binding by the UBA domain of the mRNA export factor Mex67. Molecular biology of the cell 23 17475778
2011 Evolutionary development of redundant nuclear localization signals in the mRNA export factor NXF1. Molecular biology of the cell 22 21965294
2009 ICP27 phosphorylation site mutants display altered functional interactions with cellular export factors Aly/REF and TAP/NXF1 but are able to bind herpes simplex virus 1 RNA. Journal of virology 22 20015986
2009 Structural requirements for the ubiquitin-associated domain of the mRNA export factor Mex67 to bind its specific targets, the transcription elongation THO complex component Hpr1 and nucleoporin FXFG repeats. The Journal of biological chemistry 21 19401465
2010 Head-to-tail intramolecular interaction of herpes simplex virus type 1 regulatory protein ICP27 is important for its interaction with cellular mRNA export receptor TAP/NXF1. mBio 20 21060739
2019 The general mRNA exporters Mex67 and Mtr2 play distinct roles in nuclear export of tRNAs in Trypanosoma brucei. Nucleic acids research 19 31392978
2001 Retroviral constitutive transport element evolved from cellular TAP(NXF1)-binding sequences. Journal of virology 18 11356964
2014 Gammaretroviral pol sequences act in cis to direct polysome loading and NXF1/NXT-dependent protein production by gag-encoded RNA. Retrovirology 17 25212909
2007 Formation of a Tap/NXF1 homotypic complex is mediated through the amino-terminal domain of Tap and enhances interaction with nucleoporins. Molecular biology of the cell 14 17978099
2020 Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm7 complex. eLife 13 33095156
2014 MLV requires Tap/NXF1-dependent pathway to export its unspliced RNA to the cytoplasm and to express both spliced and unspliced RNAs. Retrovirology 13 24597485
2008 A genetic screen in Saccharomyces cerevisiae identifies new genes that interact with mex67-5, a temperature-sensitive allele of the gene encoding the mRNA export receptor. Molecular genetics and genomics : MGG 13 19034519
2022 Evidence for Viral mRNA Export from Ebola Virus Inclusion Bodies by the Nuclear RNA Export Factor NXF1. Journal of virology 12 36040180
2020 URH49 exports mRNA by remodeling complex formation and mediating the NXF1-dependent pathway. Biochimica et biophysica acta. Gene regulatory mechanisms 11 31917363
2009 Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing. PLoS genetics 11 19436707
2004 Conserved nuclear export sequences in Schizosaccharomyces pombe Mex67 and human TAP function in mRNA export by direct nuclear pore interactions. The Journal of biological chemistry 11 14963046
2024 Cellular NS1-BP protein interacts with the mRNA export receptor NXF1 to mediate nuclear export of influenza virus M mRNAs. The Journal of biological chemistry 9 39384042
2020 Dbp5 associates with RNA-bound Mex67 and Nab2 and its localization at the nuclear pore complex is sufficient for mRNP export and cell viability. PLoS genetics 9 33002012
2017 RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling. Scientific reports 9 28578407
2015 Nxf1 natural variant E610G is a semi-dominant suppressor of IAP-induced RNA processing defects. PLoS genetics 8 25835743
2015 Structural characterization of the principal mRNA-export factor Mex67-Mtr2 from Chaetomium thermophilum. Acta crystallographica. Section F, Structural biology communications 8 26144233
2009 Dm nxf1/sbr gene affects the formation of meiotic spindle in female Drosophila melanogaster. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 8 19779841
2019 Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress-dependent mRNAs. EMBO reports 7 31680439
2020 Germline heterozygous mutations in Nxf1 perturb RNA metabolism and trigger thrombocytopenia and lymphopenia in mice. Blood advances 6 32236527
2014 Recombinant expression, purification and preliminary characterization of the mRNA export factor MEX67 of Saccharomyces cerevisiae. Protein expression and purification 5 25462802
2010 Interchromatin granule clusters of the scorpionfly oocytes contain poly(A)+ RNA, heterogeneous ribonucleoproteins A/B and mRNA export factor NXF1. Cell biology international 5 20658966
2015 Intranuclear binding in space and time of exon junction complex and NXF1 to premRNPs/mRNPs in vivo. The Journal of cell biology 4 26459599
2010 Alternative transcripts expressed by small bristles, the Drosophila melanogaster nxf1 gene. Gene 4 20214956
2016 Cytoplasmic localization of SBR (Dm NXF1) protein and its zonal distribution in the ganglia of Drosophila melanogaster larvae. Invertebrate neuroscience : IN 3 27389771
2025 Allostery and inter-domain dynamics in NXF1: An insight into viral CTE-RNA binding. International journal of biological macromolecules 2 39988168
2025 MIR4726EccDNA drives bortezomib resistance in multiple myeloma by enhancing MIR4726-5p/NXF1/NKIRAS2 axis dependent autophagy. Cell communication and signaling : CCS 2 40682103
2025 NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicing. iScience 2 40792019
2023 Mutations in the NXF-1:NXT-1 mRNA export complex affect gene-expression driven by the hsp-16.41 promoter. microPublication biology 2 37583452
2015 [THE ROLE OF sbr/Dm nxf1 GENE DURING SYNCYTIAL PERIODS OF DEVELOPMENT IN DROSOPHILA MELANOGASTER]. Tsitologiia 2 26349247
2010 [Spermatogenesis in Drosophila melanogaster: the role of the basic transport receptor of the mRNA (Dm NXF1)]. Tsitologiia 2 20799623
2007 Schizosaccharomyces pombe nup97, which Genetically Interacts with mex67, is essential for growth and involved in mRNA export. Journal of microbiology (Seoul, Korea) 2 17846589
2021 The RNA-Binding Protein SBR (Dm NXF1) Is Required for the Constitution of Medulla Boundaries in Drosophila melanogaster Optic Lobes. Cells 1 34068524
2026 Division of labor in trypanosome RNA processing and export through expanded Mex67 paralogs. Nucleic acids research 0 41495905
2026 An elevated level of the mRNA exporter Mex67-Mtr2 in nuclear mRNPs impairs nuclear mRNA export. Nucleic acids research 0 41574433
2025 Assessment of the preventive effect of knockdown of cellular genes NXF1, PRPS1PRPS1 and NAA10 in influenza infection in an in vitro model. Voprosy virusologii 0 40233338
2025 The TAP/NXF1-Binding Region of HuD Is Required for Translation and Neuronal Differentiation. Genes to cells : devoted to molecular & cellular mechanisms 0 41110461
2024 Interaction of CDK12 with NXF1 is a new node for the linking mechanism between transcription and transportation of mRNA. Biochemical and biophysical research communications 0 39270556

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