Affinage

UPF1

Regulator of nonsense transcripts 1 · UniProt Q92900

Length
1129 aa
Mass
124.3 kDa
Annotated
2026-04-28
100 papers in source corpus 56 papers cited in narrative 56 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UPF1 is an ATP-dependent 5'-to-3' RNA helicase and RNP remodeling enzyme that serves as the central effector of nonsense-mediated mRNA decay (NMD) and multiple additional RNA surveillance and degradation pathways. UPF1 binds RNA promiscuously and is displaced from coding sequences by translating ribosomes, accumulating on 3' UTRs where aberrant translation termination (sensed via eRF1/eRF3 and the exon-junction complex through UPF2/UPF3) triggers SMG1-mediated phosphorylation at Ser-Gln motifs; phosphorylated UPF1 recruits SMG5–SMG7 (phospho-dependent) and SMG6 endonuclease (predominantly phospho-independent via the helicase domain) to execute mRNA degradation, while PP2A-mediated dephosphorylation resets the cycle (PMID:1748286, PMID:23832275, PMID:25184677, PMID:14636577, PMID:25013172). Its ATPase activity is essential for target discrimination—selectively releasing UPF1 from non-target mRNAs—and for processive translocation (>10 kb) that remodels entire mRNPs; dual intramolecular autoinhibition by the CH domain and C-terminal SQ domain is relieved by UPF2 binding, switching UPF1 from an RNA-clamping to an RNA-unwinding mode (PMID:26253027, PMID:26138914, PMID:21419344, PMID:23275559). Beyond NMD, UPF1 participates in Staufen-mediated decay (via STAU1/STAU2), histone mRNA decay (via SLBP/ATR), glucocorticoid receptor-mediated decay (via PNRC2), Regnase-1-mediated inflammatory mRNA decay, structure-mediated decay (with G3BP1), m6A-dependent decay (via YTHDF2), and TSN-mediated miRNA decay; it also functions as an E3 ubiquitin ligase through its RING-like CH domain to ubiquitinate MYOD and repress myogenesis, promotes R-loop formation at DNA double-strand breaks to stimulate homologous recombination, and supports telomere replication through interaction with TPP1 and DNA polymerase delta (PMID:15680326, PMID:16086026, PMID:25775514, PMID:31329944, PMID:32017897, PMID:35613594, PMID:28827400, PMID:28669802, PMID:34158508, PMID:21829167).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1991 High

    The discovery that yeast UPF1 is specifically required for rapid degradation of PTC-containing mRNAs established UPF1 as the founding factor of nonsense-mediated mRNA decay, answering whether a dedicated gene product surveils translation termination fidelity.

    Evidence Genetic deletion of UPF1 in yeast with Northern blot mRNA half-life measurement

    PMID:1748286

    Open questions at the time
    • Mechanism of PTC recognition unknown
    • Whether UPF1 acts directly on RNA or through intermediaries unclear
    • No mammalian ortholog yet identified
  2. 1995 High

    Demonstration that UPF1 co-sediments with polyribosomes and that its NMD substrates include cytoplasmically exported pre-mRNAs associated with ribosomes linked UPF1 function to ongoing translation in the cytoplasm.

    Evidence Sucrose gradient fractionation, immunofluorescence, and Northern blot in yeast UPF1 mutants

    PMID:7545033 PMID:8346213

    Open questions at the time
    • Whether UPF1 directly contacts ribosomes or RNA
    • Enzymatic activity not yet characterized
  3. 1996 High

    Identification that a UPF1 allele (mof4-1) simultaneously inactivates NMD and increases ribosomal frameshifting revealed that UPF1 modulates translation termination fidelity, not just mRNA decay.

    Evidence Frameshifting reporter assays and NMD reporter analysis with mof4-1 allele in yeast

    PMID:8896465

    Open questions at the time
    • Structural basis for dual function unknown
    • Whether this extends to mammals
  4. 2000 High

    Biochemical reconstitution of purified human UPF1 established it as an RNA-dependent ATPase and 5'-to-3' helicase whose RNA binding is modulated by ATP, providing the first enzymatic framework for how UPF1 acts on substrate RNAs.

    Evidence In vitro ATPase, helicase, and RNA-binding assays with purified recombinant human UPF1

    PMID:10999600

    Open questions at the time
    • How ATPase/helicase activities relate to NMD function in vivo
    • No structural information yet
  5. 2003 High

    Discovery that phosphorylated UPF1 recruits SMG5–SMG7 which in turn deliver PP2A for UPF1 dephosphorylation established the phosphorylation–dephosphorylation cycle as an essential regulatory mechanism for NMD, building on earlier C. elegans genetic epistasis showing SMG proteins control UPF1 phosphorylation state.

    Evidence Co-immunoprecipitation, phosphatase assays, dominant-negative overexpression in mammalian cells; Western blot phospho-isoform detection in C. elegans smg mutants

    PMID:10454541 PMID:12554878 PMID:14636577

    Open questions at the time
    • Identity of the kinase (later shown to be SMG1) not fully resolved in these studies
    • Phosphorylation sites on UPF1 not mapped
    • How phosphorylation communicates with decay machinery downstream of dephosphorylation
  6. 2005 High

    Identification of UPF1 as required for Staufen-mediated decay (SMD) and histone mRNA decay demonstrated that UPF1 is a general RNA decay effector beyond NMD, recruited by distinct adaptor proteins (STAU1, SLBP/ATR) to degrade non-PTC-containing mRNAs.

    Evidence Co-immunoprecipitation of STAU1–UPF1, RNAi knockdown with mRNA half-life measurement for SMD and histone mRNA substrates

    PMID:15680326 PMID:16086026

    Open questions at the time
    • How UPF1 is recruited in each pathway mechanistically distinct from NMD
    • Whether helicase activity is required for these non-NMD pathways
  7. 2006 High

    Crystal structures of the UPF1 helicase core and CH domain revealed the molecular architecture—two RecA-like domains with an RNA channel, and RING/U-box-related zinc-finger modules—explaining how ATP binding destabilizes RNA contacts and how the CH domain mediates UPF2 interaction.

    Evidence X-ray crystallography in multiple nucleotide-bound states with site-directed mutagenesis

    PMID:16931876 PMID:17159905

    Open questions at the time
    • Structure of full-length UPF1 with RNA not available
    • CH domain autoinhibition mechanism not yet resolved
  8. 2006 High

    Demonstration that UPF1 depletion causes S-phase arrest and ATR-dependent DNA damage response, and that UPF1 associates with chromatin and DNA polymerase delta, established a DNA replication role independent of NMD.

    Evidence shRNA knockdown, cell cycle analysis, chromatin fractionation, in vitro kinase assay, co-immunoprecipitation in human cells

    PMID:12000843 PMID:16488880

    Open questions at the time
    • Whether the replication role requires helicase activity
    • Direct mechanism at replication forks unknown
  9. 2008 High

    Mapping UPF1 interactions with eRF1, eRF3, and the EJC (via UPF2 or UPF3b) provided an integrated model for how premature termination is sensed: UPF1 inhibits termination while PABPC1 stimulates it, and EJC proximity triggers SMG1-mediated phosphorylation.

    Evidence Co-immunoprecipitation, pull-down assays, reporter mRNA functional assays with mutational analysis

    PMID:18256688

    Open questions at the time
    • Kinetic parameters of competitive PABPC1/UPF1 binding not established
    • How EJC position quantitatively determines NMD efficiency
  10. 2011 High

    Crystal structures of UPF1 with and without the CH domain in an RNA-bound ATP-transition state revealed that the CH domain clamps RNA in the absence of UPF2, and UPF2 binding triggers a large conformational change that switches UPF1 from RNA clamping to unwinding mode, resolving the autoinhibition mechanism.

    Evidence X-ray crystallography in multiple states with in vitro ATPase and helicase assays

    PMID:21419344

    Open questions at the time
    • How the CH-domain conformational switch is coordinated with phosphorylation in vivo
    • Whether UPF2-independent activation routes exist
  11. 2012 High

    Discovery of a second intramolecular inhibitory mechanism—the C-terminal SQ domain directly impeding helicase domain ATPase and unwinding activities—established that UPF1 is maintained in a doubly autoinhibited state requiring multiple activating inputs.

    Evidence In vitro ATPase, helicase, and RNA-binding assays with truncation and domain mutants of recombinant UPF1

    PMID:23275559

    Open questions at the time
    • Which NMD factor(s) relieve SQ-domain inhibition in vivo
    • Structural basis for SQ-helicase domain interaction not resolved
  12. 2013 High

    Transcriptome-wide iCLIP mapping showed UPF1 binds RNA promiscuously and is displaced from coding sequences by translating ribosomes, accumulating on 3' UTRs, fundamentally revising the model from 'targeted recruitment' to 'ribosome-mediated sculpting' of UPF1 distribution.

    Evidence iCLIP at single-nucleotide resolution with translation inhibition experiments in human cells

    PMID:23832275

    Open questions at the time
    • How promiscuous binding is reconciled with NMD target specificity at the single-mRNA level
    • Kinetics of UPF1 displacement by ribosomes not measured
  13. 2014 High

    Multiple studies converged to show that UPF1 ATPase activity is the key determinant of NMD target discrimination: ATPase-dead UPF1 accumulates indiscriminately on both target and non-target mRNAs with hyperphosphorylation, whereas wild-type UPF1 selectively releases from non-targets, establishing the 'kinetic proofreading' model.

    Evidence CLIP-seq with ATPase mutants, in vitro RNA binding/release assays, FRET, transcriptome-wide phospho-UPF1 footprinting

    PMID:25184677 PMID:26253027

    Open questions at the time
    • What molecular features of NMD targets prevent ATP-dependent release
    • Whether kinetic proofreading parameters differ across transcript classes
  14. 2014 High

    Structural and biochemical dissection of how phosphorylated UPF1 recruits decay factors revealed that SMG5–SMG7 binds via 14-3-3-like phospho-dependent recognition of C-terminal SQ motifs, while SMG6 primarily uses a phosphorylation-independent interaction with the UPF1 helicase domain stalk, providing the mechanistic basis for parallel decay routes.

    Evidence In vitro reconstitution with purified proteins, crystal structure of SMG6 14-3-3-like domain, pull-down assays, mutational analysis

    PMID:25013172 PMID:25053839

    Open questions at the time
    • How SMG5–SMG7 and SMG6 pathways are coordinated or compete on a single mRNP
    • Whether all SQ sites contribute equally
  15. 2015 High

    Single-molecule experiments demonstrated UPF1 is a highly processive RNA translocase (>10 kb) capable of traversing double-stranded structures and protein obstacles, establishing that once recruited, UPF1 can remodel an entire mRNP irreversibly.

    Evidence Single-molecule magnetic tweezers with purified UPF1 and bulk helicase/ATPase assays

    PMID:26138914

    Open questions at the time
    • How processivity is regulated in the cellular context with co-factors
    • Whether other helicases (e.g., MOV10) coordinate with UPF1 processivity in vivo
  16. 2017 High

    Discovery that UPF1's CH/RING domain functions as an E3 ubiquitin ligase targeting MYOD for proteasomal degradation to repress myogenesis established a protein-level regulatory function wholly independent of RNA decay.

    Evidence Ubiquitination assays with RING domain mutants, RNAi knockdown, myogenesis differentiation assays

    PMID:28669802

    Open questions at the time
    • Full substrate repertoire of UPF1 E3 ligase activity unknown
    • Whether ubiquitin ligase and NMD functions are coordinated or mutually exclusive
  17. 2019 High

    Identification of UPF1 as required for Regnase-1-mediated inflammatory mRNA decay (RMD) showed that UPF1 unwinds stem-loop substrates prior to Regnase-1 cleavage, with SMG1-phosphorylated T28 mediating the interaction, linking UPF1 phosphorylation to inflammatory gene regulation.

    Evidence Single-molecule imaging, co-immunoprecipitation, SMG1 inhibitor treatment, phospho-site mapping

    PMID:31329944

    Open questions at the time
    • Whether all Regnase-1 substrates require UPF1
    • How T28 phosphorylation is regulated independently of canonical SQ sites
  18. 2020 High

    UPF1 and G3BP1 were shown to mediate structure-mediated decay (SRD), degrading mRNAs and circular RNAs based on overall 3' UTR secondary structure rather than specific sequence motifs, expanding UPF1's role to a general structure-sensing decay factor.

    Evidence Genome-wide RNA decay analysis, RNAi knockdown, reporter assays with structured/unstructured 3' UTRs

    PMID:32017897

    Open questions at the time
    • How UPF1 distinguishes structured from unstructured 3' UTRs at the molecular level
    • Whether SRD and NMD can operate on the same transcript
  19. 2021 High

    Demonstration that UPF1 drives R-loop formation at DNA double-strand breaks to stimulate DNA resection and homologous recombination established a direct role for UPF1 in DNA repair beyond its previously known replication and telomere functions.

    Evidence DRIP (DNA-RNA immunoprecipitation), RNAi knockdown, HR and MMEJ repair assays, checkpoint activation assays

    PMID:34158508

    Open questions at the time
    • Whether UPF1 helicase activity is required for R-loop formation at DSBs
    • Mechanism by which UPF1 promotes R-loop formation rather than resolution
  20. 2022 High

    Characterization of the UPF1LL isoform (11-residue longer regulatory loop) showed it bypasses protective RNA-binding proteins to target transcripts normally shielded from NMD, and is preferentially active during the integrated stress response, revealing isoform-specific rewiring of mRNA surveillance.

    Evidence Biochemical RNA binding assays, transcriptome-wide analyses, stress response induction, isoform-specific analyses, crystal structure comparison

    PMID:29378013 PMID:35403729

    Open questions at the time
    • How isoform ratio is regulated across tissues and conditions
    • Whether UPF1LL has distinct roles in non-NMD decay pathways

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full mechanism by which UPF1 integrates its diverse functions—NMD target discrimination via ATPase-driven kinetic proofreading, E3 ligase activity, DNA repair, and multiple adaptor-recruited decay pathways—within a single cell remains unresolved, particularly how pathway choice is determined on individual mRNPs and how nuclear versus cytoplasmic pools are regulated.
  • No single-molecule visualization of UPF1 pathway choice on individual mRNPs in living cells
  • Structural basis for SQ-domain autoinhibition relief not resolved
  • How UPF1 nuclear functions (R-loop formation, telomere maintenance, E3 ligase) are coordinated with cytoplasmic mRNA decay roles

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0003723 RNA binding 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 10 R-HSA-392499 Metabolism of proteins 3 R-HSA-69306 DNA Replication 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1640170 Cell Cycle 1 R-HSA-1852241 Organelle biogenesis and maintenance 1 R-HSA-73894 DNA Repair 1
Partners
PNRC2SMG1SMG5SMG6SMG7STAU1STAU2UPF2
Complex memberships
SMG1C-UPF1-UPF2 complexSURF complex (SMG1-UPF1-eRF1-eRF3)UPF1-UPF2-UPF3 complex

Evidence

Reading pass · 56 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Yeast UPF1 gene product is required for rapid turnover of mRNAs containing a premature translational termination codon (nonsense-mediated mRNA decay), acting specifically in response to a premature termination signal without affecting wild-type mRNA stability. Genetic loss-of-function (upf1 deletion) with mRNA half-life measurement by Northern blot Genes & development High 1748286
1993 In yeast lacking UPF1 function, pre-mRNAs (CYH2, RP51B, MER2) are stabilized and associate with ribosomes in the cytoplasm, indicating UPF1 normally degrades cytoplasmically exported pre-mRNAs that contain early in-frame nonsense codons. Genetic loss-of-function (upf1 mutant) combined with sucrose gradient fractionation and Northern blot analysis Proceedings of the National Academy of Sciences of the United States of America High 8346213
1995 Yeast UPF1 co-localizes with polyribosomes in the cytoplasm, suggesting it associates with translating ribosomes to carry out nonsense-mediated mRNA decay. Immunofluorescence microscopy and sucrose gradient fractionation with epitope-tagged UPF1 Molecular biology of the cell High 7545033
1996 The mof4-1 allele of yeast UPF1 both inactivates NMD and increases the efficiency of -1 ribosomal frameshifting, demonstrating UPF1 modulates translation termination fidelity and frameshifting efficiency in addition to mRNA decay. Genetic allele characterization, frameshifting reporter assays, NMD reporter mRNA analysis The EMBO journal High 8896465
1997 Human HUPF1 is a cytoplasmic protein of ~130 kDa with NTPase and RNA helicase consensus motifs including putative zinc finger motifs shared with yeast UPF1, and is detected in cytoplasm but not nucleus by immunofluorescence. cDNA cloning, Western blot, immunofluorescence Nucleic acids research Medium 9064659
1999 C. elegans SMG-2 (UPF1 ortholog) is a phosphoprotein; its phosphorylation state is regulated by other SMG proteins — SMG-1, -3, -4 are required for phosphorylation while SMG-5, -6, -7 loss causes accumulation of hyperphosphorylated SMG-2, establishing a phosphorylation cycle central to NMD. Western blot with phospho-isoform detection in smg mutant backgrounds; antibody generation Molecular and cellular biology High 10454541
2000 Human UPF1 possesses RNA-dependent ATPase activity and 5'-to-3' helicase activity; its RNA-binding activity is modulated by ATP, demonstrating conservation of enzymatic activities from yeast to human. In vitro biochemical assays with purified recombinant human UPF1: ATPase assay, helicase assay, RNA-binding assay RNA (New York, N.Y.) High 10999600
2002 Human RENT1/hUPF1 is required for both nonsense-mediated mRNA decay (NMD) and nonsense-mediated altered splicing (NAS), and enters the nucleus where it may influence early mRNA biogenesis; NMD and NAS are genetically separable functions of hUPF1 as UPF2 knockdown blocks NMD but not NAS. RNAi knockdown in mammalian cells, reporter mRNA analysis, subcellular fractionation Science (New York, N.Y.) High 12228722
2002 Human UPF1 (delta helicase) physically interacts with the 66-kDa third subunit of DNA polymerase delta in vivo, suggesting a role in DNA replication. Immunoprecipitation from cell extracts Nucleic acids research Medium 12000843
2003 Phosphorylated human UPF1 forms a complex with hSMG-5 and hSMG-7, which also associates with protein phosphatase 2A (PP2A), resulting in dephosphorylation of UPF1; overexpression of hSMG-5 mutants that retain P-UPF1 binding but cannot induce dephosphorylation impairs NMD, demonstrating that the UPF1 phosphorylation/dephosphorylation cycle is required for NMD. Co-immunoprecipitation, phosphatase assays, dominant-negative overexpression Molecular cell High 14636577
2003 Human hSmg5/7a functions in dephosphorylation of UPF1 by targeting protein phosphatase 2A to UPF1, and co-purifies with UPF1, UPF2, UPF3X, SMG1, and the catalytic subunit of PP2A. Co-immunoprecipitation, phosphatase assays, Western blot RNA (New York, N.Y.) High 12554878
2005 Mammalian Staufen1 (STAU1) binds directly to UPF1 and recruits it to specific mRNA 3' UTRs to elicit mRNA decay (Staufen-mediated decay, SMD); this pathway is distinct from canonical NMD as it does not require UPF2, UPF3X, or pre-mRNA splicing, and targets natural mRNAs including ARF1 mRNA. Co-immunoprecipitation, RNA immunoprecipitation, RNAi knockdown, mRNA half-life measurement Cell High 15680326
2005 Regulated degradation of replication-dependent histone mRNAs requires UPF1 (and ATR kinase); UPF1 couples histone mRNA decay to DNA replication status. RNAi knockdown with histone mRNA half-life measurement by Northern blot Nature structural & molecular biology High 16086026
2005 CBP80 (cap-binding protein) interacts with UPF1 and promotes the interaction of UPF1 with UPF2 during the pioneer round of translation; this interaction augments NMD efficiency but not SMD. Co-immunoprecipitation, RNAi knockdown, reporter mRNA assays Nature structural & molecular biology High 16186820
2006 Crystal structure of the human UPF1 helicase core reveals two RecA-like domains with additional protruding domains; structural comparison and mutational analysis identify an ssRNA-binding channel and conformational changes coupled to ATP binding/hydrolysis that explain how ATP destabilizes RNA binding. X-ray crystallography in three nucleotide-bound states, site-directed mutagenesis The EMBO journal High 17159905
2006 Crystal structure of the cysteine-histidine-rich (CH) domain of human UPF1 at 3 Å resolution reveals a unique arrangement of three zinc-binding motifs in two tandem modules related to RING-box and U-box domains; mutational analysis identifies residues mediating interaction with UPF2. X-ray crystallography, site-directed mutagenesis, binding assays RNA (New York, N.Y.) High 16931876
2006 UPF1 is required for S phase progression and genome stability; shRNA-mediated depletion of UPF1 causes human cells to arrest early in S phase, inducing ATR-dependent DNA-damage response. A fraction of hyperphosphorylated UPF1 associates with chromatin in an ATR-dependent manner, and ATR phosphorylates UPF1 both in vitro and in vivo. UPF1 physically interacts with DNA polymerase delta. shRNA knockdown, cell cycle analysis, chromatin fractionation, in vitro kinase assay, co-immunoprecipitation Current biology : CB High 16488880
2008 UPF1 binds to eRF1 and the GTPase domain of eRF3 (in both GTP- and GDP-bound states) and inhibits translation termination, while PABPC1 stimulates it; UPF1 can interact with the EJC through either UPF2 or UPF3b to become phosphorylated and activate NMD, providing an integrated model for mammalian NMD. Co-immunoprecipitation, pull-down assays, reporter mRNA functional assays, mutational analysis The EMBO journal High 18256688
2008 The RNA editing enzyme ADAR1 and hUPF1 interact and are found associated within nuclear RNA-splicing complexes; RNAi-mediated down-regulation of ADAR1 upregulates genes that are also down-regulated by hUPF1, suggesting a regulatory connection between A-to-I editing and UPF1-mediated decay. Co-immunoprecipitation, RNAi knockdown, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 18362360
2009 Yeast UPF1 stimulates proteasome-mediated degradation of aberrant polypeptides (PTC products) derived from PTC-containing mRNAs, indicating UPF1 coordinates both mRNA and protein quality control. Western blot, pulse-chase analysis in upf1 mutant yeast EMBO reports Medium 19798102
2010 UPF1 association with CBP80 promotes NMD at two distinct steps: formation of the SURF complex (SMG1-UPF1-eRF1-eRF3) at a PTC, and subsequent association of SMG1 and UPF1 with an exon-junction complex; preventing UPF1-CBP80 interaction inhibits both steps and reduces UPF1 binding to PTC-containing mRNA. Co-immunoprecipitation, RNAi knockdown, reporter mRNA assays, mutational analysis Molecular cell High 20691628
2011 Crystal structures of Upf1 (with and without the CH domain) captured in ATP transition state with ADP:AlF4- and RNA reveal that in isolation Upf1 clamps RNA in a channel formed by catalytic and regulatory domains; upon UPF2 binding, the CH domain undergoes a large conformational change that causes the helicase domain to bind RNA less extensively and triggers helicase activity, switching UPF1 from RNA-clamping to RNA-unwinding mode. X-ray crystallography in multiple states, in vitro ATPase and helicase assays Molecular cell High 21419344
2011 Human UPF1 interacts with telomeric factor TPP1 and with telomerase; this interaction is mediated by ATR. UPF1 is present at telomeres during S and G2/M phases, and its ATPase activity is required to prevent telomeric defects that stem predominantly from inefficient telomere leading-strand replication. Co-immunoprecipitation, chromatin immunoprecipitation, cell cycle analysis, ATPase mutant analysis The EMBO journal High 21829167
2011 In yeast, two distinct Upf1-bound complexes exist: Upf1-23 (Upf1, Upf2, Upf3) and Upf1-decapping (containing decapping enzyme, Nmd4, Ebs1); Nmd4 and Ebs1 are globally required for NMD and RNA degradation mediated by the Upf1 C-terminal helicase region. Affinity purification coupled with mass spectrometry (112 experiments), genetic analysis The EMBO journal High 30275269
2012 The C-terminal SQ domain of UPF1 directly interacts with the helicase domain to impede ATP hydrolysis and RNA unwinding, providing a second intramolecular inhibitory mechanism in addition to the CH domain; UPF1 is thus maintained in an inactive state by two intramolecular inhibition mechanisms in the absence of binding partners. Biochemical assays (ATPase, helicase, RNA-binding) with truncation and domain mutants of recombinant UPF1 Nucleic acids research High 23275559
2012 STAU2, the paralog of STAU1, directly interacts with UPF1 (~10-fold more than STAU1) and promotes UPF1 helicase activity (but not ATPase activity) to reduce half-life of SMD target mRNAs; STAU2 changes the conformation of RNA-bound UPF1. Co-immunoprecipitation, in vitro helicase/ATPase assays, tethering assays, FRET, RNAi knockdown Proceedings of the National Academy of Sciences of the United States of America High 23263869
2012 hUPF1 participates in RNA silencing by interacting with hAGO1 and hAGO2 and colocalizing in processing bodies; UPF1 depletion reduces the amount of target mRNAs bound to hAGO2, suggesting UPF1 facilitates RISC binding to targets. Co-immunoprecipitation, RNA immunoprecipitation, RNAi knockdown, reporter assays Molecular and cellular biology Medium 19704008
2013 UPF1 preferentially associates with 3' UTRs in translationally active cells but redistributes toward coding sequences (CDS) upon translation inhibition, indicating UPF1 binds RNA in a translation-independent manner and is displaced from CDS by translating ribosomes, with NMD triggering occurring after UPF1 binding. iCLIP (individual-nucleotide-resolution UV crosslinking and immunoprecipitation), RNA immunoprecipitation, translation inhibition experiments Nature structural & molecular biology High 23832275
2013 SMG1 (PI3K-related kinase) directly phosphorylates UPF1 upon PTC recognition during initial round of translation; phosphorylated UPF1 recruits SMG-5/SMG-7 complex to induce decapping-mediated decay, and recruits SMG-6 endonuclease for endo-cleavage. Kinase assays, co-immunoprecipitation, RNAi knockdown Genes to cells : devoted to molecular & cellular mechanisms High 23356578
2014 Phosphorylated UPF1 (p-UPF1) provides a reliable marker of cellular NMD targets, being enriched on NMD target 3' UTRs along with SMG5 and SMG7; ATPase/helicase-deficient UPF1 manifests disregulated hyperphosphorylation and elevated RNA binding, while wild-type UPF1 uses ATP hydrolysis-dependent release from non-specific RNA to identify NMD targets. Transcriptome-wide footprinting, DNA oligonucleotide-directed mRNA cleavage, immunoprecipitation of UPF1 variants, FRET experiments Genes & development High 25184677
2014 The ATPase cycle of UPF1 is required for target mRNA discrimination during NMD; ATPase mutations lead to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. Translation and termination codon-proximal PABP depend on UPF1 ATPase activity to limit non-target association. UPF1 preferentially releases from non-target mRNAs in an ATPase-dependent manner in vitro. CLIP-seq with ATPase mutant UPF1, in vitro RNA binding/release assays, RNAi knockdown Molecular cell High 26253027
2014 A short C-terminal segment of phosphorylated UPF1 (containing the last two Ser-Gln motifs) is recognized by the SMG5-SMG7 heterodimer (14-3-3-like proteins) via phospho-dependent interaction; SMG6 interacts with UPF1 through a dominant phosphorylation-independent interaction between SMG6's low-complexity region and the UPF1 helicase domain and C-terminal tail, in addition to a weak phospho-dependent interaction. In vitro reconstitution with purified proteins, crystal structure of SMG6 14-3-3-like domain, pull-down assays, mutational analysis Nucleic acids research High 25013172
2014 SMG6 requires a novel phosphorylation-independent interaction with the stalk region of the UPF1 helicase domain (and contribution from SQ domain) for NMD; this interaction is critical for SMG6 endonuclease function in NMD. In vivo and in vitro binding assays, tethering assays, NMD factor knockdowns Nucleic acids research High 25053839
2014 The electron microscopy structures of SMG1C-UPFs complexes show that UPF2 binds SMG1C at the FRB domain in an UPF1-independent manner, and can be transferred to UPF1 within SMG1C, inducing UPF2-dependent conformational changes required to activate UPF1 within an SMG1C-UPF1-UPF2 complex. Electron microscopy, in vivo and in vitro interaction analyses, competition experiments, mutational analysis Structure (London, England : 1993) High 25002321
2014 MOV10 is a 5'-to-3' RNA helicase that interacts with UPF1 and binds to 3' UTRs upstream of predicted secondary structures; MOV10 knockdown increases mRNA half-lives of MOV10-bound and UPF1-regulated transcripts, suggesting MOV10 functions as an RNA clearance factor that resolves structures and displaces proteins from 3' UTRs to facilitate UPF1-mediated mRNA degradation. In vitro RNA unwinding assay, PAR-CLIP of MOV10 and UPF1, RNAi knockdown, mRNA half-life measurement Molecular cell High 24726324
2014 Upon inhibition of DNA replication, hyperphosphorylated UPF1 (phosphorylated by ATR and DNA-PK) competes with CTIF for SLBP binding on histone mRNPs, releasing CTIF and eIF3 from the histone mRNP; hyperphosphorylated UPF1 then recruits PNRC2 and SMG5 to trigger decapping and 5'-to-3' degradation of histone mRNAs. Co-immunoprecipitation, mRNA half-life measurement, RNAi knockdown, kinase identification Nucleic acids research High 25016523
2015 Human UPF1 is a highly processive RNA translocase (>10 kb processivity) that can translocate through double-stranded structures and protein-bound sequences, demonstrating RNP remodeling activity; once recruited to NMD target mRNAs, UPF1 can scan the entire transcript to irreversibly remodel the mRNP. Single-molecule magnetic tweezers, bulk helicase/ATPase assays Nature communications High 26138914
2015 Glucocorticoid receptor (GR), preloaded on the 5' UTR of target mRNA, recruits UPF1 through PNRC2 in a ligand-dependent manner to elicit rapid mRNA degradation (GMD); GMD is mechanistically distinct from NMD and SMD despite sharing UPF1 and PNRC2, and targets chemokine CCL2 mRNA to regulate monocyte chemotaxis. Co-immunoprecipitation, RNA immunoprecipitation, RNAi knockdown, tethering assays, mRNA half-life measurement, microarray Proceedings of the National Academy of Sciences of the United States of America High 25775514
2016 ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon; ATPase mutants accumulate 3' RNA decay fragments harboring a ribosome stalled during premature termination. This function requires ATP-binding, RNA-binding, and NMD cofactors UPF2 and UPF3. ATPase mutant analysis, ribosome sedimentation, mRNA decay intermediate analysis in yeast Nature communications High 28008922
2016 UPF1 hyperphosphorylation (at multiple Ser-Gln sites with no single site essential) increases its affinity for downstream decay machinery proportional to time of residence on target mRNA; this feedback mechanism ensures timely degradation of targets and becomes increasingly important when downstream NMD factors are depleted. Mutational analysis of phosphorylation sites, NMD reporter assays, factor depletion experiments Nature communications High 27511142
2016 GC-rich sequence motifs embedded in high GC-content regions of 3' UTRs are required for UPF1-mediated mRNA decay; reporter gene experiments demonstrate GC-rich motifs in UPF1 targets are indispensable for their degradation. BRIC-seq (RNA stability measurement), CLIP-seq, reporter gene assays with mutant 3' UTRs Genome research High 27940950
2016 The RNA helicase DHX34 functions as a scaffold bridging UPF1 and SMG1: DHX34 binds UPF1 through its core domain and SMG1 through its C-terminal domain, forming a trimeric SMG1-DHX34-UPF1 complex that promotes UPF1 phosphorylation and NMD. Electron microscopy of SMG1-DHX34 complex, truncation analysis, co-immunoprecipitation, NMD reporter assays Nature communications High 26841701
2017 UPF1 acts as an E3 ubiquitin ligase via its RING domain to promote ubiquitination and proteasomal degradation of MYOD protein (a master regulator of myogenesis), thereby repressing skeletal muscle differentiation; this is a protein decay function independent of its mRNA decay role. RNAi knockdown, overexpression, ubiquitination assay, RING domain mutant analysis, myogenesis assays Molecular cell High 28669802
2017 UPF1 helicase activity promotes Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) in cells by dissociating miRNAs from their mRNA targets, making miRNAs susceptible to TSN-mediated degradation; ~50% of candidate TumiD miRNA targets are augmented by UPF1. In vitro TSN assay without UPF1, cellular knockdown of UPF1, miRNA sequencing, AGO2-loaded miRNA experiments Genes & development High 28827400
2017 UPF1 and its interaction with STAU2 are necessary for assembly of stalled polysomes in rat hippocampal neurons and for mGluR-LTD; UPF1 regulates transport and local translation of STAU2-granule mRNAs critical for synaptic plasticity. Neuronal RNAi knockdown, polysome fractionation, synaptic plasticity assays (mGluR-LTD), live imaging The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 28821679
2018 A conserved regulatory loop in the UPF1 helicase core modulates catalytic activity; two alternatively spliced mammalian isoforms differ only in regulatory loop length, with UPF1 isoform 1 (longer loop) showing ~2-fold higher translocation and ATPase activities; crystal structure of isoform 1 helicase core in apo state reveals structural basis for differential activity. X-ray crystallography, single-molecule magnetic tweezers, biochemical ATPase/helicase assays Nucleic acids research High 29378013
2018 HTLV-1 Tax protein interacts with the central helicase core domain of UPF1, plugging the RNA channel to reduce UPF1 affinity for nucleic acids; Tax freezes RNA-bound UPF1 making it less sensitive to ATP and causing translocation defects, thereby inhibiting NMD. Single-molecule magnetic tweezers, co-immunoprecipitation, RNA binding assays, NMD reporter assays Nature communications High 29382845
2019 UPF1 is required to unwind stem-loops in Regnase-1 target inflammatory mRNAs prior to Regnase-1 endonucleolytic cleavage (Regnase-1-mediated mRNA decay, RMD); Regnase-1 physically associates with UPF1 through two points: its RNase domain binds SMG1-phosphorylated T28 of UPF1, and an intrinsically disordered segment binds the UPF1 RecA domain to enhance helicase activity. Single-molecule imaging, co-immunoprecipitation, RNAi knockdown, small-molecule SMG1 inhibition, phospho-site mapping Nucleic acids research High 31329944
2019 UPF1-mediated 3' UTR-length-dependent mRNA decay requires canonical miRNA targeting; UPF1 and SMG7 cooperate with AGO2 to recruit the CCR4-NOT deadenylase complex for miRNA-mediated mRNA destabilization (UPF1/SMG7-dependent miRNA-mediated decay). Transcriptome-wide mRNA analysis in miRNA-deficient cells with UPF1 RNAi, AGO2 immunoprecipitation, SMG7-deadenylase interaction mutant analysis Nature communications High 31519907
2019 UPF1 directly interacts with STAU1 and inhibits the STAU1-promoted replacement of nuclear cap-binding complex (CBC) by eIF4E at the 5' end of mRNAs; hyperphosphorylated UPF1 (induced by ionizing radiation) increases this inhibitory association and blocks CBC replacement. Co-immunoprecipitation, transcriptome-wide analysis, tethering assays, RNAi knockdown Nucleic acids research High 31361897
2020 UPF1 and G3BP1 mediate a structure-dependent RNA decay pathway that degrades mRNAs based on overall 3' UTR secondary structure (independent of specific sequences); depletion of either protein increases steady-state levels of mRNAs with highly structured 3' UTRs as well as structured circular RNAs. Genome-wide RNA decay analysis, RNAi knockdown, reporter assays with structured/unstructured 3' UTRs, orientation reversal controls Molecular cell High 32017897
2020 UPF1 is required for aggresome formation when the ubiquitin-proteasome system is overwhelmed; hyperphosphorylated UPF1 enables selective targeting of misfolded polypeptide aggregates to the aggresome via the CTIF-eEF1A1-DCTN1 complex, and UPF1 increases frequency and fidelity of CTIF aggregate movement toward the aggresome. Single-particle imaging, immunofluorescence, RNAi knockdown, aggresome formation assays, co-immunoprecipitation Nature communications High 32561765
2020 C9orf72 arginine-rich dipeptide repeats (poly-GR, poly-PR) inhibit UPF1-dependent RNA decay (including NMD) primarily by causing global translational repression rather than by directly inhibiting UPF1; overexpression of UPF1, but not its NMD-deficient mutants, enhances survival of neurons treated by R-DPRs. NMD reporter assays, RNAi knockdown, translation assays, neuronal survival assays with UPF1 mutants Nature communications High 32620797
2021 UPF1 drives formation of R loops and DNA-RNA hybrids at DNA double-strand breaks (DSBs), stimulating DNA resection, homologous recombination, microhomology-mediated end joining, and DNA damage checkpoint activation; R loop formation is independent of DNA resection. R loop detection assays (DRIP), RNAi knockdown, DNA repair assays (HR, MMEJ), checkpoint activation assays Nature communications High 34158508
2022 UPF1 interacts with YTHDF2 (m6A reader protein) through a specific interaction with YTHDF2 N-terminal residues 101-168 to trigger rapid degradation of m6A-containing RNAs; this decay depends on UPF1 ATPase/helicase activities and UPF1 interaction with PNRC2. Co-immunoprecipitation, RNAi knockdown, mRNA stability assay, transcriptome-wide analysis, mutational analysis Cell reports High 35613594
2022 An alternative mammalian-specific isoform of UPF1, UPF1LL (with an 11-residue longer regulatory loop), can bypass protective RNA-binding proteins PTBP1 and hnRNP L to bind and downregulate transcripts with long 3' UTRs normally shielded from NMD; UPF1LL activity is enhanced (while canonical NMD is abolished) upon integrated stress response activation, enabling NMD rewiring. Biochemical RNA binding assays, transcriptome-wide analyses, stress response induction, isoform-specific analyses The EMBO journal High 35403729

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay. Cell 422 15680326
1991 The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Genes & development 416 1748286
2003 Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Molecular cell 278 14636577
2008 Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways. The EMBO journal 259 18256688
1993 Stabilization and ribosome association of unspliced pre-mRNAs in a yeast upf1- mutant. Proceedings of the National Academy of Sciences of the United States of America 236 8346213
2011 Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2. Molecular cell 233 21419344
2002 Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. Science (New York, N.Y.) 221 12228722
2020 Structure-Mediated RNA Decay by UPF1 and G3BP1. Molecular cell 215 32017897
2013 Global analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decay. Genome research 214 23766421
1999 SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast. Molecular and cellular biology 199 10454541
2005 Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1. Nature structural & molecular biology 178 16086026
2006 The human RNA surveillance factor UPF1 is required for S phase progression and genome stability. Current biology : CB 175 16488880
2006 UPF1 is required for nonsense-mediated mRNA decay (NMD) and RNAi in Arabidopsis. The Plant journal : for cell and molecular biology 168 16813578
2019 UPFront and center in RNA decay: UPF1 in nonsense-mediated mRNA decay and beyond. RNA (New York, N.Y.) 166 30655309
2014 MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs. Molecular cell 158 24726324
2000 Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay. RNA (New York, N.Y.) 155 10999600
2014 A post-translational regulatory switch on UPF1 controls targeted mRNA degradation. Genes & development 142 25184677
2016 Upregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101-3p and interacting with UPF1 in hepatocellular carcinoma. Cancer letters 139 27702662
2006 Structural and functional insights into the human Upf1 helicase core. The EMBO journal 138 17159905
2013 Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3' UTRs. Nature structural & molecular biology 136 23832275
2003 Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. RNA (New York, N.Y.) 135 12554878
2012 Identification of hundreds of novel UPF1 target transcripts by direct determination of whole transcriptome stability. RNA biology 133 23064114
1997 Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein. Nucleic acids research 130 9064659
2005 CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nature structural & molecular biology 125 16186820
2015 Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities. Nature communications 120 26138914
1995 The majority of yeast UPF1 co-localizes with polyribosomes in the cytoplasm. Molecular biology of the cell 118 7545033
2014 The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma. Nature medicine 106 24859531
2015 Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1. Proceedings of the National Academy of Sciences of the United States of America 104 26056265
2010 UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps. Molecular cell 95 20691628
2015 Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity. Molecular cell 93 26253027
2014 Phospho-dependent and phospho-independent interactions of the helicase UPF1 with the NMD factors SMG5-SMG7 and SMG6. Nucleic acids research 89 25013172
2008 Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation. RNA (New York, N.Y.) 87 18369187
2006 Arabidopsis UPF1 RNA helicase for nonsense-mediated mRNA decay is involved in seed size control and is essential for growth. Plant & cell physiology 77 16540482
2006 Crystal structure of the UPF2-interacting domain of nonsense-mediated mRNA decay factor UPF1. RNA (New York, N.Y.) 77 16931876
2011 Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication. The EMBO journal 74 21829167
2014 A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD. Nucleic acids research 73 25053839
2006 Specific inhibition of nonsense-mediated mRNA decay components, SMG-1 or Upf1, rescues the phenotype of Ullrich disease fibroblasts. Molecular therapy : the journal of the American Society of Gene Therapy 72 16807116
2012 Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity. Proceedings of the National Academy of Sciences of the United States of America 71 23263869
2012 The human T-lymphotropic virus type 1 tax protein inhibits nonsense-mediated mRNA decay by interacting with INT6/EIF3E and UPF1. Journal of virology 70 22553336
2017 The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 69 28942451
2016 A GC-rich sequence feature in the 3' UTR directs UPF1-dependent mRNA decay in mammalian cells. Genome research 69 27940950
2014 Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD. Structure (London, England : 1993) 69 25002321
2016 The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 68 26759305
2016 Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay. Nature communications 66 27511142
2010 Expression proteomics of UPF1 knockdown in HeLa cells reveals autoregulation of hnRNP A2/B1 mediated by alternative splicing resulting in nonsense-mediated mRNA decay. BMC genomics 65 20946641
2014 Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis. Gene therapy 64 25354681
2012 Tight intramolecular regulation of the human Upf1 helicase by its N- and C-terminal domains. Nucleic acids research 62 23275559
2013 Role of SMG-1-mediated Upf1 phosphorylation in mammalian nonsense-mediated mRNA decay. Genes to cells : devoted to molecular & cellular mechanisms 60 23356578
2011 Nonsense-mediated mRNA decay factors, UPF1 and UPF3, contribute to plant defense. Plant & cell physiology 60 22025558
2009 Upf1 stimulates degradation of the product derived from aberrant messenger RNA containing a specific nonsense mutation by the proteasome. EMBO reports 60 19798102
2021 Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis. ASN neuro 58 33906483
2015 Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation. Proceedings of the National Academy of Sciences of the United States of America 58 25775514
1996 Mof4-1 is an allele of the UPF1/IFS2 gene which affects both mRNA turnover and -1 ribosomal frameshifting efficiency. The EMBO journal 57 8896465
2020 LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2. Molecular oncology 55 31919993
2015 HIV-1 Recruits UPF1 but Excludes UPF2 to Promote Nucleocytoplasmic Export of the Genomic RNA. Biomolecules 52 26492277
2006 The double life of UPF1 in RNA and DNA stability pathways. Cell cycle (Georgetown, Tex.) 49 16861888
2016 ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons. Nature communications 48 28008922
2022 UPF1 promotes rapid degradation of m6A-containing RNAs. Cell reports 47 35613594
2019 Translation-dependent unwinding of stem-loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs. Nucleic acids research 47 31329944
2017 Sen1 has unique structural features grafted on the architecture of the Upf1-like helicase family. The EMBO journal 47 28408439
2007 Caenorhabditis elegans SMG-2 selectively marks mRNAs containing premature translation termination codons. Molecular and cellular biology 47 17562857
2020 C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression. Nature communications 46 32620797
2018 The UPF1 interactome reveals interaction networks between RNA degradation and translation repression factors in Arabidopsis. The Plant journal : for cell and molecular biology 46 29983000
2018 Nonsense-mediated mRNA decay involves two distinct Upf1-bound complexes. The EMBO journal 46 30275269
2021 UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair. Nature communications 44 34158508
2017 The RNA Surveillance Factor UPF1 Represses Myogenesis via Its E3 Ubiquitin Ligase Activity. Molecular cell 43 28669802
2012 Arabidopsis plants having defects in nonsense-mediated mRNA decay factors UPF1, UPF2, and UPF3 show photoperiod-dependent phenotypes in development and stress responses. Journal of integrative plant biology 43 22353561
2012 Up-frameshift protein 1 (UPF1): multitalented entertainer in RNA decay. Drug discoveries & therapeutics 41 22622014
2008 The editing enzyme ADAR1 and the mRNA surveillance protein hUpf1 interact in the cell nucleus. Proceedings of the National Academy of Sciences of the United States of America 41 18362360
2016 The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation. Nature communications 40 26841701
2020 GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation. eLife 39 33006314
2018 A conserved structural element in the RNA helicase UPF1 regulates its catalytic activity in an isoform-specific manner. Nucleic acids research 37 29378013
2020 The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1. Theranostics 34 32802196
2022 Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway. Cellular and molecular gastroenterology and hepatology 33 35863742
2014 The mRNP remodeling mediated by UPF1 promotes rapid degradation of replication-dependent histone mRNA. Nucleic acids research 33 25016523
2019 UPF1 inhibits the hepatocellular carcinoma progression by targeting long non-coding RNA UCA1. Scientific reports 32 31040354
2012 Evidence that the Upf1-related molecular motor scans the 3'-UTR to ensure mRNA integrity. Nucleic acids research 32 22554850
2021 UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer. Cell death & disease 31 34021129
2019 LncRNA DANCR aggravates the progression of ovarian cancer by downregulating UPF1. European review for medical and pharmacological sciences 31 31858532
2018 HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition. Nature communications 31 29382845
2022 An alternative UPF1 isoform drives conditional remodeling of nonsense-mediated mRNA decay. The EMBO journal 30 35403729
2020 UPF1-Mediated RNA Decay-Danse Macabre in a Cloud. Biomolecules 30 32635561
2017 UPF1 helicase promotes TSN-mediated miRNA decay. Genes & development 30 28827400
2018 The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level. Retrovirology 29 29954456
2022 UPF1/circRPPH1/ATF3 feedback loop promotes the malignant phenotype and stemness of GSCs. Cell death & disease 28 35871061
2020 Nonsense-mediated mRNA decay factor UPF1 promotes aggresome formation. Nature communications 28 32561765
2002 Identification of delta helicase as the bovine homolog of HUPF1: demonstration of an interaction with the third subunit of DNA polymerase delta. Nucleic acids research 28 12000843
2019 UPF1/SMG7-dependent microRNA-mediated gene regulation. Nature communications 26 31519907
2009 Human UPF1 participates in small RNA-induced mRNA downregulation. Molecular and cellular biology 26 19704008
2022 UPF1 contributes to the maintenance of endometrial cancer stem cell phenotype by stabilizing LINC00963. Cell death & disease 25 35318304
2020 Targeting of viral RNAs by Upf1-mediated RNA decay pathways. Current opinion in virology 24 33341474
2019 LncRNA PVT1 aggravates the progression of glioma via downregulating UPF1. European review for medical and pharmacological sciences 23 31696483
2014 Characterization of phosphorylation- and RNA-dependent UPF1 interactors by quantitative proteomics. Journal of proteome research 23 24762188
2021 UPF1: From mRNA Surveillance to Protein Quality Control. Biomedicines 22 34440199
2017 UPF1 Governs Synaptic Plasticity through Association with a STAU2 RNA Granule. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 28821679
2012 Biochemical characterization of the RNA helicase UPF1 involved in nonsense-mediated mRNA decay. Methods in enzymology 22 22713324
2013 Phosphorylation of the N- and C-terminal UPF1 domains plays a critical role in plant nonsense-mediated mRNA decay. The Plant journal : for cell and molecular biology 21 24118551
2012 UPF1 involvement in nuclear functions. Biochemical Society transactions 21 22817733
2011 Interactions between Upf1 and the decapping factors Edc3 and Pat1 in Saccharomyces cerevisiae. PloS one 21 22065998
2019 Staufen1 and UPF1 exert opposite actions on the replacement of the nuclear cap-binding complex by eIF4E at the 5' end of mRNAs. Nucleic acids research 20 31361897