Affinage

UPF1

Regulator of nonsense transcripts 1 · UniProt Q92900

Length
1129 aa
Mass
124.3 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UPF1 is a conserved, ATP-dependent SF1-family RNA/DNA helicase that serves as the central effector of nonsense-mediated mRNA decay (NMD) and a broader set of UPF1-dependent decay pathways (PMID:7489520, PMID:10999600, PMID:8346213). Its catalytic core contains two RecA-like domains whose conformation is coupled to the nucleotide state: ATP binding and hydrolysis remodel an ssRNA-binding channel so that nucleic-acid binding in the absence of ATP gives way to release upon hydrolysis (PMID:17159905, PMID:7489520). In isolation UPF1 clamps RNA via its catalytic and regulatory N-terminal CH domain; binding of UPF2 drives a large CH-domain conformational change that switches UPF1 from an RNA-clamping mode to a processive RNA-unwinding/translocating mode, and UPF2/UPF3b cooperatively stimulate its ATPase and helicase activities within a reconstituted EJC-containing heptamer (PMID:21419344, PMID:18066079, PMID:26138914). UPF1 binds RNA in a translation-independent manner and is displaced from coding sequences by translating ribosomes, accumulating on 3' UTRs (PMID:23832275). Target discrimination is achieved kinetically: ATP-hydrolysis-driven cycles preferentially dissociate UPF1 from non-target mRNAs, and protective factors such as poly(A)-binding protein and PTBP1 promote this ATPase-dependent release, while helicase processivity itself is dispensable for decay of canonical targets (PMID:26253027, PMID:32571872, PMID:36370101). Upon aberrant termination, SMG1 kinase—scaffolded by DHX34 and regulated by SMG8/SMG9—phosphorylates UPF1 on C-terminal SQ motifs (PMID:26841701, PMID:26130714, PMID:10454541); phospho-UPF1 enriched on NMD-target 3' UTRs then recruits SMG5–SMG7 (directing PP2A-mediated dephosphorylation and decapping) and SMG6 (endonucleolytic cleavage via both phospho-dependent and phospho-independent contacts), with cyclical phosphorylation/dephosphorylation required for productive decay (PMID:25184677, PMID:14636577, PMID:25013172, PMID:12554664). ATP hydrolysis by UPF1 is additionally required for efficient ribosome release at premature termination codons (PMID:28008922). Beyond canonical NMD, UPF1 drives Staufen-mediated decay through direct STAU1/STAU2 binding that stimulates its helicase activity (PMID:15680326, PMID:23263869), G3BP1-dependent structure-mediated decay (PMID:32017897), YTHDF2-coupled m6A RNA decay (PMID:35613594), replication-dependent histone mRNA decay (PMID:25016523), and AGO-coupled miRNA turnover (PMID:19704008, PMID:28827400), and it acts as a RING-domain E3 ubiquitin ligase targeting MYOD for proteasomal degradation (PMID:28669802). In the nucleus, UPF1 associates with chromatin in S phase in an ATR-dependent manner, interacts with DNA polymerase delta and TPP1/telomerase, and promotes R-loop formation at double-strand breaks, supporting DNA replication, telomere maintenance, and repair (PMID:16488880, PMID:21829167, PMID:34158508).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1995 High

    Establishing UPF1's molecular activity: was it an enzyme, and on what substrate? Biochemical purification showed it is an ATP-dependent helicase, defining the catalytic machine at the heart of NMD.

    Evidence In vitro NTPase, helicase, and nucleic-acid binding assays with yeast Upf1p purified from extract

    PMID:7489520

    Open questions at the time
    • Substrate specificity in vivo not defined
    • Coupling of ATPase to mRNA decay not yet linked
    • No structural basis for ATP-dependent release
  2. 1993 High

    Connecting UPF1 to a cellular process: loss-of-function stabilized PTC-containing transcripts, identifying UPF1 as required for degradation of nonsense-codon-bearing mRNAs.

    Evidence mRNA half-life and polyribosome analysis in upf1-deletion yeast

    PMID:8346213

    Open questions at the time
    • Mechanism of PTC recognition unknown
    • How helicase activity links to decay not established
  3. 1996 High

    Dissecting domain function: active-site and CH-domain mutagenesis separated ATP binding from hydrolysis in RNA release and established the Upf1–Upf2–Upf3 hierarchy, showing helicase and partner-binding functions are separable.

    Evidence Site-directed mutagenesis with in vitro ATPase/helicase/binding assays and yeast two-hybrid

    PMID:8816461 PMID:8816462

    Open questions at the time
    • Structural basis of CH-domain regulation unknown
    • How Upf2 binding alters catalysis not yet shown
  4. 1999 High

    Defining post-translational regulation: UPF1 is a phosphoprotein whose phosphorylation depends on SMG-1 and whose dephosphorylation depends on SMG-5/6/7, placing a phospho-cycle at the core of NMD control.

    Evidence Western blot mobility-shift epistasis across seven C. elegans smg mutants

    PMID:10454541

    Open questions at the time
    • Phosphosites not mapped
    • Kinase mechanism and recruitment not defined
  5. 2000 High

    Testing conservation: recombinant human UPF1 recapitulated yeast ATPase and 5'→3' helicase activity, confirming the catalytic mechanism is conserved to mammals.

    Evidence In vitro ATPase/helicase/RNA-binding assays with recombinant human UPF1

    PMID:10999600

    Open questions at the time
    • In-cell substrate engagement not addressed
  6. 2002 High

    Separating UPF1 functions: RNAi epistasis showed NMD and nonsense-mediated altered splicing are genetically distinct UPF1 activities, and UPF1 was detected in the nucleus, hinting at roles beyond cytoplasmic decay.

    Evidence siRNA double-knockdown with NMD/NAS reporters and nuclear fractionation in mammalian cells

    PMID:12228722

    Open questions at the time
    • Mechanism of nuclear UPF1 function unresolved
    • Molecular basis of NAS unknown
  7. 2003 High

    Resolving how phospho-UPF1 is decoded: SMG5/SMG7 recruit PP2A specifically to UPF1, and phospho-dependent SMG5–SMG7 complexes are mechanistically required for NMD cycles of phosphorylation/dephosphorylation.

    Evidence Reciprocal Co-IP, phosphatase assays, and dominant-negative overexpression in human and C. elegans systems

    PMID:12554664 PMID:12554878 PMID:12723973 PMID:14636577

    Open questions at the time
    • Stoichiometry and order of recruitment not resolved
    • EJC/eRF3 absent from steady-state complexes left their role unclear
  8. 2006 High

    Providing a structural mechanism: crystal structures of the human helicase core in three nucleotide states explained how ATP binding remodels the ssRNA channel to destabilize RNA binding.

    Evidence X-ray crystallography (phosphate/AMPPNP/ADP) with RNA-channel mutagenesis

    PMID:17159905

    Open questions at the time
    • CH-domain regulation not captured
    • RNA-bound state not yet solved
  9. 2006 High

    Uncovering a nuclear genome-maintenance role: UPF1 depletion caused S-phase arrest and ATR-dependent DNA-damage response, and UPF1 bound chromatin and DNA polymerase delta, linking it to replication.

    Evidence shRNA depletion, chromatin fractionation, in vitro ATR kinase assay, and Co-IP with pol delta

    PMID:12000843 PMID:16488880

    Open questions at the time
    • Direct enzymatic role at replication forks not defined
    • Relationship to cytoplasmic NMD pool unclear
  10. 2005 High

    Extending UPF1 beyond NMD: direct Staufen1 binding triggers Staufen-mediated decay independently of UPF2/UPF3, showing UPF1 is a shared effector recruited by distinct adaptors.

    Evidence Co-IP for direct binding, tethering for sufficiency, and siRNA knockdown of natural target Arf1

    PMID:15680326

    Open questions at the time
    • Mechanism distinguishing SMD from NMD targets unknown
    • Whether helicase activity is required not yet shown
  11. 2007 High

    Defining cofactor activation: reconstitution of an EJC–UPF complex showed UPF2/UPF3b cooperatively stimulate UPF1 ATPase and helicase activity, providing a biochemical basis for activation upon target engagement.

    Evidence In vitro reconstitution of a recombinant heptameric complex with ATPase/helicase assays

    PMID:18066079

    Open questions at the time
    • Relevance to EJC-independent NMD not addressed
    • In-cell assembly order not defined
  12. 2007 High

    Ordering recognition relative to phosphorylation: SMG-2/UPF1 selectively marks PTC-containing mRNPs in a phosphorylation-independent manner, placing target recognition upstream of the phospho-cycle.

    Evidence mRNP immunoprecipitation/RT-PCR of endogenous substrates across C. elegans smg mutants

    PMID:17562857

    Open questions at the time
    • Molecular feature defining a PTC-mRNP not identified
    • How marking triggers phosphorylation unclear
  13. 2011 High

    Revealing the regulatory conformational switch: structures with transition-state analog and RNA showed UPF1 clamps RNA via the CH domain until Upf2 binding switches it to an unwinding mode, explaining cofactor-gated activation.

    Evidence X-ray crystallography (ADP:AlF4-/RNA) with ATPase/helicase assays plus Upf2

    PMID:21419344

    Open questions at the time
    • Timing of the switch on real targets not resolved
    • Link between mode-switch and decay output not yet quantified
  14. 2011 High

    Anchoring the nuclear role at telomeres: UPF1 binds TPP1 and telomerase in an ATR-stimulated, cell-cycle-staged manner, and its ATPase activity prevents leading-strand telomere replication defects.

    Evidence Co-IP, ChIP, staged fractionation, ATPase-mutant complementation, and telomere FISH

    PMID:21829167

    Open questions at the time
    • Whether UPF1 acts catalytically at telomeres unknown
    • Substrate nucleic acid at telomeres not defined
  15. 2013 High

    Establishing the spatial logic of binding: CLIP-seq showed translation-independent RNA binding with displacement from CDS by ribosomes and 3' UTR accumulation, framing how UPF1 surveys transcripts.

    Evidence iCLIP-seq with translation inhibition in human cells; yeast two-hybrid/binding identifying Rps26 contact

    PMID:23801788 PMID:23832275

    Open questions at the time
    • What converts 3' UTR occupancy into a decay decision not resolved by binding maps alone
  16. 2014 High

    Identifying the cellular NMD-target marker and the role of late factors: phospho-UPF1 marks NMD-target 3' UTRs, and distinct SMG5–SMG7 versus dual-mode SMG6 interactions explain phospho-dependent dephosphorylation/decapping versus endonucleolysis.

    Evidence Transcriptome-wide footprinting, oligo-directed cleavage, FRET, mutant IP, crystallography of SMG6 14-3-3-like domain, and tethering assays

    PMID:25013172 PMID:25053839 PMID:25184677

    Open questions at the time
    • Switch between SMG6 endonucleolytic and SMG5/7 deadenylation/decapping branches not fully resolved
    • How phospho-pattern selects branch unclear
  17. 2014 Medium

    Extending UPF1 to replication-coupled histone mRNA turnover: hyperphosphorylated UPF1 displaces CTIF/eIF3 from SLBP and recruits PNRC2/SMG5 to drive decapping, linking DNA-replication stress kinases to mRNA decay.

    Evidence Co-IP, competitive binding, knockdown, and mRNA stability assays

    PMID:25016523

    Open questions at the time
    • Single-lab mechanism
    • Direct role of ATR/DNA-PK phosphosites not mapped on UPF1
  18. 2015 High

    Quantifying the motor and defining kinetic proofreading: UPF1 is a highly processive translocase that remodels RNPs, and ATPase-driven selective dissociation from non-targets—aided by PABP—provides target discrimination.

    Evidence Single-molecule magnetic tweezers, bulk helicase assays, ATPase-cycle mutants, and transcriptome-wide binding/in vitro dissociation assays

    PMID:26138914 PMID:26253027

    Open questions at the time
    • Physiological structures UPF1 unwinds in vivo not catalogued
    • How proofreading integrates with phosphorylation not unified
  19. 2016 High

    Linking UPF1 catalysis to termination and mapping the kinase-recruitment network: ATP hydrolysis promotes ribosome release at PTCs, DHX34 scaffolds SMG1–UPF1, SMG8/SMG9 tune SMG1 activity and stringency, and hyperphosphorylation provides feedback amplification.

    Evidence Ribosome profiling with ATPase mutants, cryo-EM of SMG1-8-9-UPF1, in vitro kinase assays, and phosphomimetic/phospho-null reporter assays

    PMID:26130714 PMID:26841701 PMID:27511142 PMID:28008922

    Open questions at the time
    • In-cell trigger that initiates SMG1 phosphorylation not pinpointed
    • Multi-site phospho-code remains undeciphered
  20. 2017 High

    Demonstrating a moonlighting protein-degradation activity: UPF1 functions as a RING-domain E3 ubiquitin ligase that degrades MYOD protein independently of mRNA stability, expanding its repertoire to protein quality control.

    Evidence RING-domain mutant, in vivo ubiquitination, protein-stability, and myogenesis assays

    PMID:28669802

    Open questions at the time
    • Broader E3 substrate range unknown
    • Structural basis of RING activity not defined
  21. 2017 High

    Linking helicase activity to small-RNA pathways: UPF1 dissociates miRNAs from targets to enable TSN-mediated miRNA decay, with phenotypic consequences for cell invasion.

    Evidence siRNA depletion, miRNA-seq, in vitro AGO2-loaded duplex dissociation, and invasion assays

    PMID:19704008 PMID:28827400

    Open questions at the time
    • How UPF1 is recruited to specific miRNA-mRNA duplexes unclear
    • Relationship to canonical NMD machinery not defined
  22. 2018 High

    Defining the biophysical determinant of function and a viral inhibitory strategy: nucleic-acid grip tightness sets UPF1 processivity and NMD efficiency, while HTLV-1 Tax freezes RNA-bound UPF1 to inhibit NMD.

    Evidence Single-molecule binding-lifetime assays with grip mutants, in vivo NMD reporters, and magnetic-tweezers analysis of Tax-bound UPF1

    PMID:29382845 PMID:30218034

    Open questions at the time
    • Other viral/host modulators of grip not surveyed
    • Whether grip differences explain target selectivity not tested
  23. 2018 High

    Resolving complex composition: yeast Upf1 exists in distinct Upf1-23 (Upf1/2/3) and Upf1-decapping complexes, with Nmd4/Ebs1 acting as functional analogs of mammalian SMG5-7 for C-terminal-helicase-mediated decay.

    Evidence Large-scale AP-MS (112 experiments) with genetic NMD analysis of nmd4/ebs1 mutants

    PMID:30275269

    Open questions at the time
    • Mammalian counterpart organization of the two complexes not directly compared
    • Order of complex interconversion unresolved
  24. 2019 Medium

    Strengthening the nuclear/gene-expression role and broadening Staufen-coupled mechanisms: UPF1 binds nascent Pol II transcripts and aids their release/export, while STAU2 binds UPF1 more tightly than STAU1 and stimulates its helicase activity, and phospho-UPF1/STAU1 regulates CBC-to-eIF4E replacement.

    Evidence Polytene microscopy/ChIP-seq with helicase mutants in Drosophila; in vitro helicase and conformation assays with STAU2; transcriptome-wide CBC-replacement assay

    PMID:23263869 PMID:30907728 PMID:31361897

    Open questions at the time
    • Conservation of nascent-RNA role to mammals not established
    • Mechanistic link between nuclear binding and decay outcomes unclear
  25. 2020 High

    Cataloguing adaptor-defined decay and protein-quality functions: UPF1 with G3BP1 drives structure-mediated decay, PTBP1 promotes ATPase-dependent UPF1 release to protect mRNAs, and hyperphospho-UPF1 routes misfolded proteins to the aggresome.

    Evidence Structure-swapping reporter assays with G3BP1/UPF1 knockdown; in vitro helicase and mRNP-dissociation assays with PTBP1 and domain-1B mutants; single-particle imaging of aggregate trafficking

    PMID:32017897 PMID:32561765 PMID:32571872

    Open questions at the time
    • Shared versus distinct recruitment logic across decay branches not unified
    • Aggresome-targeting mechanism single-lab
  26. 2022 High

    Connecting UPF1 to m6A decay and isoform-specific regulation: UPF1 partners with YTHDF2 (via PNRC2 and its ATPase/helicase) to degrade m6A RNAs, and a mammalian UPF1LL isoform with altered RNA-release kinetics targets long-3'UTR mRNAs shielded from canonical NMD, activated under integrated stress.

    Evidence Domain-mapped Co-IP and mutant analysis with transcriptome-wide stability assays; in vitro RNA-dissociation and ISR-induction comparison of UPF1SL vs UPF1LL

    PMID:35403729 PMID:35613594

    Open questions at the time
    • Physiological conditions selecting isoform usage not fully mapped
    • Coordination among parallel decay pathways unresolved
  27. 2022 High

    Decoupling helicase processivity from decay: UPF1 mutants with impaired processivity but intact ATPase still support NMD, reinforcing that ATPase-driven binding/release cycles—not unwinding per se—govern accurate target selection.

    Evidence High-throughput biochemical helicase screens, in-cell NMD reporters, and single-molecule analysis of multiple mutants

    PMID:36370101

    Open questions at the time
    • Roles where processivity is required (e.g., RNP remodeling targets) not delineated
    • How discrimination integrates with phosphorylation not unified
  28. 2021 Medium

    Establishing a direct DNA-repair function: UPF1 promotes R-loop/DNA-RNA hybrid formation at double-strand breaks, stimulating resection, HR, MMEJ, and checkpoint activation independently of resection.

    Evidence R-loop detection at DSBs, UPF1 knockdown, and HR/MMEJ repair and checkpoint assays

    PMID:34158508

    Open questions at the time
    • Whether UPF1 catalyzes hybrid formation directly unknown
    • Single-lab; relationship to its replication/telomere roles unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the single UPF1 enzyme is selectively partitioned among its many adaptor-defined RNA-decay pathways, nuclear genome-maintenance roles, and E3 ligase activity—and how its multi-site phospho-code and ATPase cycle are integrated to set each output—remains unresolved.
  • No unified model linking phospho-code to pathway choice
  • Determinants of nuclear versus cytoplasmic function not defined
  • Quantitative competition among adaptors (STAU, G3BP1, YTHDF2, AGO) not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 9 GO:0140098 catalytic activity, acting on RNA 6 GO:0003723 RNA binding 5 GO:0003677 DNA binding 3 GO:0016787 hydrolase activity 3 GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005840 ribosome 2
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-392499 Metabolism of proteins 2 R-HSA-69306 DNA Replication 2 R-HSA-1266738 Developmental Biology 1 R-HSA-1640170 Cell Cycle 1 R-HSA-73894 DNA Repair 1
Partners
DHX34SMG1SMG5SMG6SMG7STAU1UPF2UPF3B
Complex memberships
SMG1-SMG8-SMG9-UPF1 complexUPF1-UPF2-UPF3 surveillance complexUpf1-decapping complex (with Nmd4/Ebs1)exon-junction complex (EJC) heptamer with UPF1/2/3b

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Yeast Upf1p possesses RNA-dependent ATPase activity, RNA and DNA helicase activities, and RNA/DNA binding activity. In the absence of ATP, Upf1p binds single-stranded RNA or DNA; ATP hydrolysis facilitates release from single-stranded nucleic acid. Biochemical purification from yeast extract; in vitro NTPase, helicase, and nucleic acid binding assays RNA High 7489520
1996 Mutations in the conserved helicase motifs of yeast Upf1p (e.g., DE572AA in the ATP binding/hydrolysis motif) abolish ATPase and helicase activities and cause the mutant to form a stable RNA complex in the absence of ATP; ATP binding (independent of hydrolysis) can dissociate this complex, indicating that ATP binding and hydrolysis play separable roles in RNA release. Site-directed mutagenesis combined with in vitro ATPase, helicase, and RNA-binding assays Molecular and cellular biology High 8816461
1996 Mutations in the N-terminal cysteine/histidine-rich (CH) domain of yeast Upf1p abolish interaction with Upf2p (detected by two-hybrid), and Upf2p interacts with Upf3p, establishing the Upf1p–Upf2p–Upf3p complex hierarchy. CH-domain mutations allow nonsense suppression without disrupting NMD, demonstrating separable functional domains. Yeast two-hybrid; in vitro binding; genetic analysis of NMD and nonsense suppression phenotypes Molecular and cellular biology High 8816462
1995 Yeast Upf1p co-sediments with polyribosomes in the cytoplasm, co-localizing with ribosomal protein L1; association with 80S particles is detected upon polyribosome disaggregation, placing Upf1 at the ribosome during translation. Sucrose gradient sedimentation; immunofluorescence with epitope-tagged UPF1-3EP; co-fractionation under conditions that alter polyribosome profiles Molecular biology of the cell High 7545033
1993 In yeast upf1 mutants, cytoplasmic pre-mRNAs (CYH2, RP51B, MER2) that contain early in-frame nonsense codons are stabilized 2–5-fold and associate with ribosomes, identifying pre-mRNAs as natural NMD substrates and establishing Upf1 as required for their degradation. mRNA half-life measurement in upf1 deletion yeast; polyribosome fractionation; Northern blotting Proceedings of the National Academy of Sciences of the United States of America High 8346213
1999 C. elegans SMG-2 (UPF1 ortholog) is a phosphoprotein; other smg genes regulate its phosphorylation state. In smg-1, smg-3, smg-4 mutants, phosphorylation of SMG-2 is undetectable; in smg-5, smg-6, smg-7 mutants and in SMG-2 nucleotide-binding-site mutants, hyperphosphorylated SMG-2 accumulates, establishing that SMG-1 is required for phosphorylation and SMG-5/6/7 are required for dephosphorylation. Western blotting with anti-SMG-2 antibodies in smg mutant backgrounds; SDS-PAGE mobility shift to detect phosphorylation Molecular and cellular biology High 10454541
2000 Human UPF1 (HUpf1/RENT1) displays nucleic acid-dependent ATPase activity and 5'→3' RNA helicase activity; its RNA-binding activity is modulated by ATP, consistent with conservation of catalytic mechanism from yeast. Expression, purification, and in vitro ATPase, helicase, and RNA-binding assays with recombinant human UPF1 RNA High 10999600
2002 RNAi-mediated depletion of rent1/hUpf1 in mammalian cells abrogates both NMD and nonsense-mediated altered splicing (NAS), whereas depletion of rent2/hUpf2 abrogates NMD but not NAS, demonstrating that NAS and NMD are genetically separable functions of hUpf1. Additionally, hUpf1 was detected in the nucleus, suggesting it influences early mRNA biogenesis events. RNA interference in mammalian cells; RT-PCR for NMD and NAS reporter transcripts; nuclear fractionation/immunofluorescence Science High 12228722
2003 Phosphorylated hUPF1 forms a complex with hSMG-5 and hSMG-7; this complex also contains protein phosphatase 2A (PP2A), which dephosphorylates hUPF1. Overexpression of hSMG-5 mutants that bind P-hUPF1 but cannot induce dephosphorylation impairs NMD, establishing that cycles of UPF1 phosphorylation and dephosphorylation are mechanistically required for NMD. Co-immunoprecipitation; phosphatase assays; dominant-negative overexpression; Western blotting Molecular cell High 14636577
2003 Human hSmg5/7a co-purifies with Upf1, Upf2, Upf3X, Smg1, and the catalytic subunit of PP2A; hSmg5/7a functions in dephosphorylation of Upf1 but not Upf2, indicating it targets PP2A specifically to Upf1. Affinity co-purification; immunoprecipitation; in vitro phosphatase assays RNA High 12554878
2003 Human Upf1 forms stable complexes with Upf2 and Upf3a/b (detected by affinity chromatography and mass spectrometry) in a ~1.3 MDa high-molecular-mass complex; poly(A)-binding protein associates with Upf1 in an RNA-dependent manner. Components of the exon-junction complex and eRF3 were not detected in steady-state Upf1 complexes. Double-affinity tag purification from stable HeLa cell line; mass spectrometry; size-exclusion chromatography; RNase sensitivity experiment The Biochemical journal Medium 12723973
2003 C. elegans SMG-5 interacts with SMG-2 (UPF1), SMG-7, PP2A structural subunit PR65, and PP2A catalytic subunit, establishing that SMG-5 recruits PP2A to SMG-2 for dephosphorylation. Immunoprecipitation; yeast two-hybrid The EMBO journal High 12554664
2005 Mammalian Staufen1 (Stau1) binds directly to UPF1 and, when tethered downstream of a termination codon, elicits mRNA decay (Staufen-mediated decay, SMD). SMD does not require pre-mRNA splicing and occurs independently of Upf2/Upf3X; Arf1 mRNA is a natural SMD target stabilized when either Stau1 or Upf1 is downregulated. Co-immunoprecipitation (direct Stau1–UPF1 binding); tethering assay; siRNA knockdown of Stau1 or Upf1; mRNA stability measurements Cell High 15680326
2006 Crystal structure of the human Upf1 helicase core (SF1 family) in phosphate-, AMPPNP-, and ADP-bound states reveals two RecA-like domains plus two additional domains; conformational changes coupled to ATP binding and hydrolysis alter an ssRNA-binding channel, explaining how ATP binding destabilizes ssRNA binding. X-ray crystallography; mutational analysis of RNA-binding channel The EMBO journal High 17159905
2006 shRNA-mediated depletion of human UPF1 causes S-phase arrest and ATR-dependent DNA-damage response. A fraction of hyperphosphorylated UPF1 associates with chromatin during S phase and upon γ-irradiation in an ATR-dependent manner. ATR phosphorylates UPF1 in vitro and in vivo. UPF1 physically interacts with DNA polymerase delta, suggesting a role in DNA replication/repair. shRNA depletion; FACS cell-cycle analysis; chromatin fractionation; in vitro kinase assay; co-immunoprecipitation with DNA pol delta Current biology High 16488880
2007 Recombinant EJC core (MAGOH, Y14, eIF4AIII) reconstitutes a stable heptameric complex on RNA with UPF1, UPF2, and UPF3b in vitro. The EJC provides a composite binding site for UPF3b, which bridges to UPF2 and UPF1. Within this complex, UPF2 and UPF3b cooperatively stimulate both ATPase and RNA helicase activities of UPF1. In vitro reconstitution with recombinant proteins; gel filtration; ATPase and helicase assays Nature structural & molecular biology High 18066079
2007 C. elegans SMG-2 preferentially and selectively associates with PTC-containing mRNAs ('marking') in a manner enhanced by SMG-3 and SMG-4; neither SMG-2 phosphorylation nor dephosphorylation is required for this selective marking, placing recognition of PTC-mRNPs upstream of phosphorylation. Immunoprecipitation of mRNPs followed by RT-PCR; analysis of endogenous alternatively spliced transcripts in smg mutants Molecular and cellular biology High 17562857
2008 UPF1 is a component of the HIV-1 RNP (co-purifies with Gag and viral genomic RNA); depletion of UPF1 reduces HIV-1 RNA and Gag protein, and rescue with siRNA-resistant UPF1 restores Gag synthesis, indicating UPF1 positively influences HIV-1 RNA translatability. This effect requires ATPase activity but is separable from NMD and does not require UPF2 interaction. siRNA knockdown; siRNA-rescue; overexpression; nuclear/cytoplasmic fractionation; ATPase mutant analysis RNA Medium 18369187
2008 ADAR1 and hUpf1 co-associate within nuclear RNA splicing complexes; RNAi-mediated knockdown of ADAR1 up-regulates a subset of genes previously shown to be down-regulated by hUpf1, suggesting coordinated regulation. Co-immunoprecipitation from nuclear splicing complexes; RNAi knockdown; gene expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 18362360
2009 Human UPF1 promotes miRNA-mediated silencing: UPF1 depletion up-regulates miRNA targets; overexpression of wild-type but not helicase-domain mutant UPF1 down-regulates miRNA targets. UPF1 interacts with hAGO1 and hAGO2 and co-localizes with them in processing bodies; AGO2-bound target mRNA amounts are reduced when UPF1 is depleted. siRNA knockdown; overexpression of WT and helicase mutant; co-immunoprecipitation with AGO1/2; immunofluorescence co-localization; RNA immunoprecipitation Molecular and cellular biology Medium 19704008
2011 Crystal structures of yeast Upf1 in transition-state (ADP:AlF₄⁻) and RNA-bound forms reveal that in isolation Upf1 clamps onto RNA via both catalytic and regulatory CH domains. Upon Upf2 binding, the CH domain undergoes a large conformational change, causing the helicase domain to bind RNA less extensively and switching Upf1 from an RNA-clamping mode to an RNA-unwinding mode. X-ray crystallography with ADP:AlF₄⁻ and RNA; in vitro ATPase and helicase assays with Upf2 Molecular cell High 21419344
2011 Human UPF1 interacts physically with the telomeric factor TPP1 and with telomerase; these interactions are stimulated by ATR. UPF1 associates with telomeres during S and G2/M phases; its ATPase activity is required to prevent telomeric defects that arise predominantly from inefficient telomere leading-strand replication. Co-immunoprecipitation; ChIP; cell-cycle-staged fractionation; ATPase mutant complementation; telomere FISH The EMBO journal High 21829167
2013 Transcriptome-wide CLIP-seq in human cells shows that UPF1 preferentially associates with 3' UTRs in translationally active cells but redistributes toward coding sequences (CDS) upon translation inhibition, demonstrating translation-independent RNA binding that is displaced from CDS by translating ribosomes. iCLIP-seq; RNA immunoprecipitation; translation inhibition experiments Nature structural & molecular biology High 23832275
2013 Yeast Upf1 CH domain interacts specifically with the 40S ribosomal protein Rps26, identified by two-hybrid screen and confirmed by in vitro binding assays. Upf1–40S association is modulated by ATP and is independent of eRF1, eRF3, Upf2, or Upf3. Affinity purification of ribosomal subunits; co-immunoprecipitation; yeast two-hybrid; in vitro binding assays; ATP modulation experiments RNA High 23801788
2014 Phosphorylated UPF1 (p-UPF1) is enriched on NMD target 3' UTRs (mapped by transcriptome-wide footprinting and oligonucleotide-directed mRNA cleavage) together with SMG5 and SMG7 but not SMG1 or SMG6, providing the first reliable marker of cellular NMD targets. ATPase/helicase-deficient UPF1 shows high RNA binding and dysregulated hyperphosphorylation; wild-type UPF1 releases from non-specific RNA in an ATP hydrolysis-dependent manner. SMG5 and SMG7 stabilize p-UPF1 binding to NMD target 3' UTRs. Transcriptome-wide RNA footprinting; oligonucleotide-directed mRNA cleavage; FRET; immunoprecipitation of UPF1 variants; ATPase mutant analysis Genes & development High 25184677
2014 SMG6 interacts with UPF1 via two distinct modes: (1) a phospho-dependent interaction between the SMG6 14-3-3-like domain and the last two SQ motifs of UPF1's C-terminal tail, and (2) a dominant phosphorylation-independent interaction between a low-complexity region of SMG6 and the helicase domain plus C-terminal tail of UPF1. In contrast, SMG5–SMG7 heterodimer recognizes only the C-terminal phospho-SQ motifs of UPF1. These non-overlapping binding modes were recapitulated in vitro with purified components. In vitro reconstitution with purified proteins; crystal structure of SMG6 14-3-3-like domain; co-immunoprecipitation Nucleic acids research High 25013172
2014 SMG6 requires a phosphorylation-independent interaction with the UPF1 helicase stalk region (plus a contribution from the SQ domain) for its endonucleolytic activity and NMD function; tethering assays show SMG6-mediated RNA decay requires this UPF1 interaction as well as SMG1. Tethering assays; in vivo and in vitro interaction assays; knockdown of NMD factors; deletion mutant analysis Nucleic acids research High 25053839
2014 Upon histone mRNA degradation, hyperphosphorylated UPF1 (by ATR and DNA-PK activated upon DNA-replication inhibition) competes with CTIF for SLBP binding, displacing CTIF and eIF3 from histone mRNPs; hyperphosphorylated UPF1 then recruits PNRC2 and SMG5, triggering decapping and 5'→3' degradation of histone mRNAs. Co-immunoprecipitation; competitive binding assay; knockdown experiments; mRNA stability assays Nucleic acids research Medium 25016523
2015 Human Upf1 is a highly processive RNA helicase/translocase, able to translocate >10 kb on single-stranded nucleic acids and efficiently traverse double-stranded structures and protein-bound sequences (RNP remodeling), using single-molecule magnetic tweezers and bulk helicase assays. Single-molecule magnetic tweezers; bulk RNA helicase assays Nature communications High 26138914
2015 Upf1 ATPase cycle mutations disrupt mRNA selectivity, causing indiscriminate accumulation of NMD complexes on both NMD targets and non-targets. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro identifies selective release as the mechanism of target discrimination. Poly(A)-binding protein proximal to the termination codon limits Upf1–non-target association via Upf1 ATPase activity. ATPase cycle mutants; transcriptome-wide UPF1 binding analysis; in vitro dissociation assays; ribosome footprinting Molecular cell High 26253027
2015 A network involving SMG-8, SMG-9, and the SMG-1 C-terminal insertion domain regulates UPF1 recruitment and phosphorylation: cryo-EM of the SMG-1-8-9-UPF1 complex shows UPF1 docked at the SMG-1 kinase domain and C-insertion domain, inducing head-domain opening for active-site access. SMG-8 and SMG-9 promote high-affinity UPF1 binding but decelerate kinase activity and enhance phosphorylation-site stringency. UPF2 presence destabilizes the SMG-1-8-9-UPF1 complex, promoting substrate release. Electron cryo-microscopy; in vitro kinase assays; biochemical binding assays with truncated/mutant proteins Nucleic acids research High 26130714
2016 ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon; UPF1 ATPase mutants accumulate 3' RNA decay fragments bearing a stalled ribosome at the PTC, blocking complete mRNA degradation. This function requires ATP-binding, RNA-binding, and cofactors UPF2 and UPF3. UPF1 ATPase mutant analysis; ribosome profiling; mRNA decay assays in yeast Nature communications High 28008922
2016 UPF1 hyperphosphorylation (at multiple C-terminal SQ motifs, with no single site being essential) increases affinity for downstream decay machinery. Slowing NMD by inhibiting late-acting factors triggers UPF1 hyperphosphorylation; hyperphosphorylation becomes increasingly important for NMD when downstream factors are depleted, establishing a feedback amplification mechanism. Phosphomimetic/phospho-null mutant analysis; NMD reporter assays; depletion of downstream NMD factors; quantitative interaction assays Nature communications High 27511142
2016 The RNA helicase DHX34 functions as a scaffold that simultaneously binds UPF1 (via its core) and SMG1 kinase (via its C-terminal domain, CTD); truncation of the DHX34 CTD preserves UPF1 binding but abrogates SMG1 binding, UPF1 phosphorylation, and NMD, demonstrating that DHX34 scaffolds the SMG1–UPF1 interaction to promote phosphorylation. Truncation mutant analysis; co-immunoprecipitation; electron microscopy of SMG1–DHX34 complex; 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, thereby repressing skeletal muscle differentiation. This activity is independent of MYOD mRNA stability and represents a UPF1 function in protein quality control. Knockdown and overexpression of UPF1; RING-domain mutant; in vivo ubiquitination assay; protein stability assay; myogenesis phenotype Molecular cell High 28669802
2017 UPF1 helicase activity promotes TSN-mediated miRNA decay (TumiD): UPF1 dissociates miRNAs from their mRNA targets (making them susceptible to TSN), and ~50% of candidate TumiD targets in T24 cells require UPF1 for efficient decay. This was functionally linked to promotion of cell invasion via degradation of anti-invasive miRNAs. siRNA depletion; miRNA-seq; in vitro miRNA-mRNA duplex dissociation assay with AGO2-loaded miRNAs; invasion assay Genes & development High 28827400
2018 HTLV-1 Tax interacts with the central helicase core domain of UPF1, reducing its nucleic acid affinity. Single-molecule experiments show that Tax freezes RNA-bound UPF1 in a state less sensitive to ATP and with translocation defects, thereby inhibiting NMD to promote viral gene expression. Co-immunoprecipitation; single-molecule magnetic tweezers; bulk helicase assays; NMD reporter assays Nature communications High 29382845
2018 Single-molecule analysis shows UPF1 tightly grips nucleic acids enabling long residence time and processivity; UPF1 mutants with decreased grip show reduced processivity and impaired NMD in vivo, demonstrating that grip tightness dictates helicase processivity and NMD efficiency. A three-state model (bound, sliding, unbound) predicts helicase processivity modulation. Single-molecule DNA-binding lifetime assays; in vivo NMD reporter assays with grip mutants; comparison with IGHMBP2 Nature communications High 30218034
2018 Mass spectrometry-based characterization of yeast Upf1 complexes identifies two distinct Upf1-containing complexes: Upf1-23 (Upf1, Upf2, Upf3) and Upf1-decapping (Upf1 with the decapping enzyme and Nmd4/Ebs1). Nmd4 and Ebs1 are required for RNA degradation mediated by the Upf1 C-terminal helicase region and are functionally analogous to mammalian SMG5-7. Affinity purification coupled to mass spectrometry (112 experiments); genetic analysis of NMD in nmd4/ebs1 mutants The EMBO journal High 30275269
2019 UPF1 associates genome-wide with nascent RNAs at active RNA Pol II transcription sites in Drosophila (co-localization on polytene chromosomes, ChIP-seq in S2 cells) in a manner requiring its RNA helicase activity. UPF1 shuttles between nucleus and cytoplasm; cells depleted of UPF1 show defects in release of mRNAs from transcription sites and their nuclear export. Microscopy on polytene chromosomes; ChIP-seq; nuclear export assay; UPF1 helicase mutant analysis eLife Medium 30907728
2019 Staufen2 (STAU2) binds directly to UPF1 (~10-fold more than STAU1), promotes UPF1 helicase activity without enhancing ATPase activity (depending on ATP binding and basal ATPase), and changes the conformation of RNA-bound UPF1. STAU1–STAU1, STAU2–STAU2, and STAU1–STAU2 homodimers and heterodimers form in vitro and in cells, all contributing to SMD efficiency. Co-immunoprecipitation; in vitro helicase assays with STAU2; conformation assay; tethering assay; STAU1/2 knockdown Proceedings of the National Academy of Sciences of the United States of America High 23263869
2019 Hyperphosphorylated UPF1 inhibits the replacement of the nuclear cap-binding complex (CBC) by eIF4E at the 5' end of mRNAs by competing with STAU1; STAU1 promotes CBC–importin α–importin β association for efficient replacement. Ionizing radiation-induced apoptosis is accompanied by increased STAU1–hyperphosphorylated-UPF1 association and inhibition of CBC replacement. Co-immunoprecipitation; transcriptome-wide CBC-to-eIF4E replacement assay; tethering assay; irradiation-induced apoptosis experiment Nucleic acids research Medium 31361897
2020 UPF1 and G3BP1 are required for structure-mediated RNA decay (SRD): depletion of either protein increases steady-state levels of mRNAs and circular RNAs with highly structured 3' UTRs. Decay is independent of specific sequences and is determined by overall base-pairing structure, as shown by orientation-reversal experiments and mutagenesis restoring structure. siRNA depletion; reporter mRNA stability assays with WT, reverse-complement, and mutant 3' UTRs; RNA half-life measurement Molecular cell High 32017897
2020 PTBP1 promotes ATPase-dependent dissociation of RNA-bound UPF1 from potential NMD substrates (rather than competing for binding sites) to protect mRNAs from NMD; this mechanism is exploited via a regulatory loop in domain 1B of UPF1, demonstrated by in vitro helicase assays, UPF1 mRNP dissociation assays, and transcriptome-wide UPF1 binding analysis. In vitro helicase activity assays; purified mRNP UPF1-dissociation assay; iCLIP-seq of UPF1 in PTBP1-depleted cells; domain 1B mutant analysis The Journal of biological chemistry High 32571872
2020 Hyperphosphorylated UPF1 is required for targeting NMD-polypeptide aggregates and other misfolded proteins to the aggresome via the CTIF-eEF1A1-DCTN1 complex. UPF1 hyperphosphorylation increases frequency and fidelity of CTIF aggregate movement toward the aggresome; suppression of UPF1 hyperphosphorylation increases apoptosis under proteotoxic stress. Single-particle live imaging; co-immunoprecipitation; phospho-mutant analysis; apoptosis assays Nature communications Medium 32561765
2021 UPF1 promotes the formation of R loops and DNA-RNA hybrids at sub-telomeric DNA double-strand breaks (DSBs), stimulating DNA resection, homologous recombination, microhomology-mediated end joining, and DNA damage checkpoint activation. R loop formation by UPF1 occurs independently of DNA resection. R loop detection assays at DSBs; knockdown of UPF1; HR and MMEJ repair assays; checkpoint activation assays Nature communications Medium 34158508
2021 UPF1 interacts with the bovine (and human) DNA polymerase delta third subunit (66 kDa, p66), demonstrated by co-immunoprecipitation; delta helicase (the bovine UPF1 homolog) was identified as co-purifying with pol delta and immunoinactivated by anti-HUPF1 antibodies. Affinity purification; tandem mass spectrometry; immunoprecipitation; antibody immunoinactivation Nucleic acids research Medium 12000843
2022 UPF1 interacts with the m6A-reader YTHDF2 via YTHDF2 N-terminal residues 101-168 to trigger rapid degradation of m6A-containing RNAs; this pathway requires UPF1 ATPase/helicase activities and UPF1 interaction with PNRC2 (a decapping-promoting factor). Transcriptome-wide analysis shows YTHDF2-bound mRNAs not targeted by HRSP12-RNase P/MRP endonucleolytic cleavage are preferentially destabilized in a UPF1-dependent manner. Co-immunoprecipitation; domain-mapping of YTHDF2 interaction; ATPase/helicase mutant analysis; mRNA stability assays; transcriptome-wide analysis Cell reports High 35613594
2022 An alternative mammalian-specific UPF1 isoform (UPF1LL, with extended regulatory loop in the helicase core) has decreased propensity for ATP-hydrolysis-driven RNA dissociation relative to the major isoform (UPF1SL); UPF1LL circumvents PTBP1 and hnRNP L protection to preferentially target long 3' UTR mRNAs normally shielded from NMD, and is selectively activated by integrated stress response conditions to degrade new substrate populations. Biochemical RNA-dissociation assays; transcriptome-wide RNA binding and mRNA stability analysis; integrated stress response induction; comparison of UPF1SL vs UPF1LL The EMBO journal High 35403729
2022 UPF1 mutants with substantially impaired processivity or reduced mechanochemical coupling (helicase-deficient but ATPase-intact, e.g., E797R, G619K/A546H, K547P, R549S) can still support efficient NMD of canonical targets, while ATPase activity drives cycles of RNA binding and dissociation essential for accurate NMD target selection. High-throughput biochemical helicase assays; in silico screen for mutants; NMD reporter assays in human cells; single-molecule analysis Nucleic acids research High 36370101

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 426 15680326
2003 Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Molecular cell 280 14636577
2007 NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity. Nature structural & molecular biology 274 18066079
2011 Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2. Molecular cell 238 21419344
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
2020 Structure-Mediated RNA Decay by UPF1 and G3BP1. Molecular cell 224 32017897
2002 Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. Science (New York, N.Y.) 222 12228722
2013 Global analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decay. Genome research 217 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
1996 Genetic and biochemical characterization of mutations in the ATPase and helicase regions of the Upf1 protein. Molecular and cellular biology 189 8816461
2006 The human RNA surveillance factor UPF1 is required for S phase progression and genome stability. Current biology : CB 175 16488880
2019 UPFront and center in RNA decay: UPF1 in nonsense-mediated mRNA decay and beyond. RNA (New York, N.Y.) 171 30655309
1995 Purification and characterization of the Upf1 protein: a factor involved in translation and mRNA degradation. RNA (New York, N.Y.) 163 7489520
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.) 157 10999600
2019 LncRNA SNHG6 promotes proliferation, invasion and migration in colorectal cancer cells by activating TGF-β/Smad signaling pathway via targeting UPF1 and inducing EMT via regulation of ZEB1. International journal of medical sciences 147 30662328
2014 A post-translational regulatory switch on UPF1 controls targeted mRNA degradation. Genes & development 143 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 139 17159905
2013 Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3' UTRs. Nature structural & molecular biology 138 23832275
2012 Identification of hundreds of novel UPF1 target transcripts by direct determination of whole transcriptome stability. RNA biology 135 23064114
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
1996 Identification and characterization of mutations in the UPF1 gene that affect nonsense suppression and the formation of the Upf protein complex but not mRNA turnover. Molecular and cellular biology 132 8816462
1997 Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein. Nucleic acids research 130 9064659
2015 Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities. Nature communications 122 26138914
2003 SMG-5, required for C.elegans nonsense-mediated mRNA decay, associates with SMG-2 and protein phosphatase 2A. The EMBO journal 122 12554664
1995 The majority of yeast UPF1 co-localizes with polyribosomes in the cytoplasm. Molecular biology of the cell 119 7545033
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 108 26056265
2014 The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma. Nature medicine 106 24859531
2015 Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity. Molecular cell 95 26253027
2014 Phospho-dependent and phospho-independent interactions of the helicase UPF1 with the NMD factors SMG5-SMG7 and SMG6. Nucleic acids research 90 25013172
2008 Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation. RNA (New York, N.Y.) 87 18369187
2014 A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD. Nucleic acids research 75 25053839
2011 Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication. The EMBO journal 74 21829167
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
2016 The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 70 26759305
2016 A GC-rich sequence feature in the 3' UTR directs UPF1-dependent mRNA decay in mammalian cells. Genome research 70 27940950
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 Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay. Nature communications 67 27511142
2013 Role of SMG-1-mediated Upf1 phosphorylation in mammalian nonsense-mediated mRNA decay. Genes to cells : devoted to molecular & cellular mechanisms 63 23356578
2006 Upf1, an RNA helicase required for nonsense-mediated mRNA decay, modulates the transcriptional response to oxidative stress in fission yeast. Molecular and cellular biology 63 16914721
2011 Nonsense-mediated mRNA decay factors, UPF1 and UPF3, contribute to plant defense. Plant & cell physiology 61 22025558
2021 Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis. ASN neuro 58 33906483
2022 LncRNA SNHG5 promotes the proliferation and cancer stem cell-like properties of HCC by regulating UPF1 and Wnt-signaling pathway. Cancer gene therapy 57 35338348
2020 LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2. Molecular oncology 56 31919993
2011 Drosophila Upf1 and Upf2 loss of function inhibits cell growth and causes animal death in a Upf3-independent manner. RNA (New York, N.Y.) 54 21317294
2015 A network of SMG-8, SMG-9 and SMG-1 C-terminal insertion domain regulates UPF1 substrate recruitment and phosphorylation. Nucleic acids research 52 26130714
2016 ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons. Nature communications 50 28008922
2006 The double life of UPF1 in RNA and DNA stability pathways. Cell cycle (Georgetown, Tex.) 50 16861888
2022 UPF1 promotes rapid degradation of m6A-containing RNAs. Cell reports 49 35613594
2018 UPF1-like helicase grip on nucleic acids dictates processivity. Nature communications 49 30218034
2018 Nonsense-mediated mRNA decay involves two distinct Upf1-bound complexes. The EMBO journal 48 30275269
2020 C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression. Nature communications 47 32620797
2007 Caenorhabditis elegans SMG-2 selectively marks mRNAs containing premature translation termination codons. Molecular and cellular biology 47 17562857
2021 UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair. Nature communications 46 34158508
2020 The RNA-binding protein PTBP1 promotes ATPase-dependent dissociation of the RNA helicase UPF1 to protect transcripts from nonsense-mediated mRNA decay. The Journal of biological chemistry 45 32571872
2017 The RNA Surveillance Factor UPF1 Represses Myogenesis via Its E3 Ubiquitin Ligase Activity. Molecular cell 45 28669802
2019 The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci. eLife 42 30907728
2019 UPF1 regulates the malignant biological behaviors of glioblastoma cells via enhancing the stability of Linc-00313. Cell death & disease 42 31427569
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
2021 Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1. Breast cancer research : BCR 37 34922601
2022 Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway. Cellular and molecular gastroenterology and hepatology 36 35863742
2020 The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1. Theranostics 35 32802196
2014 The mRNP remodeling mediated by UPF1 promotes rapid degradation of replication-dependent histone mRNA. Nucleic acids research 33 25016523
2021 UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer. Cell death & disease 32 34021129
2020 UPF1-Mediated RNA Decay-Danse Macabre in a Cloud. Biomolecules 32 32635561
2019 UPF1 inhibits the hepatocellular carcinoma progression by targeting long non-coding RNA UCA1. Scientific reports 32 31040354
2013 Yeast Upf1 CH domain interacts with Rps26 of the 40S ribosomal subunit. RNA (New York, N.Y.) 32 23801788
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
2017 UPF1 helicase promotes TSN-mediated miRNA decay. Genes & development 31 28827400
2022 An alternative UPF1 isoform drives conditional remodeling of nonsense-mediated mRNA decay. The EMBO journal 30 35403729
2021 UPF1 reduces C9orf72 HRE-induced neurotoxicity in the absence of nonsense-mediated decay dysfunction. Cell reports 30 33789100
2022 UPF1/circRPPH1/ATF3 feedback loop promotes the malignant phenotype and stemness of GSCs. Cell death & disease 29 35871061
2020 Nonsense-mediated mRNA decay factor UPF1 promotes aggresome formation. Nature communications 29 32561765
2018 The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level. Retrovirology 29 29954456
2020 Targeting of viral RNAs by Upf1-mediated RNA decay pathways. Current opinion in virology 28 33341474
2019 Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway. Journal of cellular and molecular medicine 28 31264769
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
2003 Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells. The Biochemical journal 27 12723973
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
2013 Identification and functional analysis of novel phosphorylation sites in the RNA surveillance protein Upf1. Nucleic acids research 25 24198248
2023 Ailanthone inhibits non-small cell lung cancer growth and metastasis through targeting UPF1/GAS5/ULK1 signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 24 38518633
2022 UPF1 mutants with intact ATPase but deficient helicase activities promote efficient nonsense-mediated mRNA decay. Nucleic acids research 23 36370101
2020 Long noncoding RNA MACC1-AS1 promotes the stemness of nonsmall cell lung cancer cells through promoting UPF1-mediated destabilization of LATS1/2. Environmental toxicology 23 32401390
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
2011 Interactions between Upf1 and the decapping factors Edc3 and Pat1 in Saccharomyces cerevisiae. PloS one 22 22065998
2022 RBM47 inhibits hepatocellular carcinoma progression by targeting UPF1 as a DNA/RNA regulator. Cell death discovery 21 35831298
2019 Effects of UPF1 expression on EMT process by targeting E‑cadherin, N‑cadherin, Vimentin and Twist in a hepatocellular carcinoma cell line. Molecular medicine reports 21 30628676
2012 UPF1 involvement in nuclear functions. Biochemical Society transactions 21 22817733
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

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