Affinage

XRN1

5'-3' exoribonuclease 1 · UniProt Q8IZH2

Length
1706 aa
Mass
194.1 kDa
Annotated
2026-06-11
100 papers in source corpus 51 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

XRN1 is a highly conserved, processive cytoplasmic 5'→3' exoribonuclease that constitutes the central engine of the 5'→3' mRNA decay pathway and broadly controls cytoplasmic RNA turnover (PMID:1398123, PMID:8417335). First identified in yeast as a non-essential gene whose loss slows growth and stabilizes short-lived mRNAs (PMID:1979303, PMID:1398123), it is an abundant, predominantly cytoplasmic enzyme conserved through to human XRN1 (PMID:7739553, PMID:9802570). Crystal structures of fungal Xrn1 define its catalytic basis: a highly basic pocket specifically recognizes the substrate 5'-monophosphate while the 5'-terminal nucleotides stack between aromatic residues, coupling processive hydrolysis to duplex melting, and a unique multi-domain insertion absent from the nuclear paralog Rat1/Xrn2 forms a platform for protein partners (PMID:21362555, PMID:21297639). Its degradative activity is intrinsically blocked by 5'-proximal RNA secondary structures, a property exploited by flaviviral xrRNA elements (pseudoknots and three-way-junction folds) that stall the enzyme to generate subgenomic sfRNA and globally repress host decay (PMID:9207242, PMID:20739539, PMID:24692447, PMID:23006624). XRN1 acts on a wide substrate range, degrading decapped mRNAs, the 3' products of RISC/siRNA cleavage, hypomodified tRNAs of the rapid tRNA decay pathway, and—via a separable deNADding activity—NAD-capped RNAs (PMID:15703439, PMID:18443146, PMID:35173156). Substrate engagement is governed by direct protein interactions: a C-terminal DCP1-binding motif couples decapping to degradation through DCP1/EDC4, a low-complexity CIR region binds the CCR4-NOT deadenylase complex and PatL1/Pat1, and the m6A reader YTHDC2 recruits XRN1 to methylated transcripts through its ankyrin repeats (PMID:23142987, PMID:31340047, PMID:29078363, PMID:29970596). A cryo-EM structure of the ribosome–Xrn1 complex shows the enzyme docked at the mRNA exit channel with the decoding site only ~17 nucleotides from its active center, establishing co-translational mRNA decay (PMID:30911188). Beyond turnover, XRN1 couples decay to transcription as a buffering factor required for synthesis–degradation feedback and modulates Pol II elongation (PMID:24119399, PMID:32518159), and it serves as a negative regulator of autophagy and of dsRNA-triggered innate immunity, where its loss permits accumulation of endogenous dsRNA from retroelements that activates PKR and RIG-I/MAVS signaling—a dependency that renders ISG-high cancer cells reliant on XRN1 (PMID:29465287, PMID:38261511, PMID:38261514, PMID:25766294). The yeast protein additionally promotes microtubule polymerization, meiotic recombination, and telomere homeostasis (PMID:7720696, PMID:1840632, PMID:28160602).

Mechanistic history

Synthesis pass · year-by-year structured walk · 48 steps
  1. 1990 High

    Established that XRN1 is a 5'→3' exoribonuclease whose loss is tolerated but growth-limiting, defining it as a non-essential RNA-degrading enzyme.

    Evidence Gene disruption and plasmid complementation in yeast with hydrolytic activity assay

    PMID:1979303

    Open questions at the time
    • No in vivo RNA substrate defined
    • Catalytic mechanism not resolved
  2. 1992 High

    Linked XRN1 directly to mRNA turnover by showing deletion stabilizes specific short-lived mRNAs, establishing its role in cytoplasmic decay.

    Evidence Northern measurement of mRNA half-lives in xrn1Δ yeast

    PMID:1398123

    Open questions at the time
    • Recruitment to substrates unknown
    • Genome-wide substrate scope undefined
  3. 1991 High

    Reported that the protein promotes homologous DNA strand exchange and is required for meiotic recombination, raising the question of a moonlighting nuclear/DNA function.

    Evidence In vitro strand exchange with purified protein plus sep1 meiotic mutant analysis

    PMID:1840632

    Open questions at the time
    • Relationship between DNA pairing and exoribonuclease activity unclear
    • In vivo relevance to recombination mechanism not separated from RNA roles
  4. 1993 High

    Distinguished cytoplasmic XRN1 from its essential nuclear paralog Rat1/Hke1 and showed they are non-redundant, partitioning 5'→3' decay into two compartments.

    Evidence In vitro activity assays, immunodepletion, and complementation failure in yeast

    PMID:8417335

    Open questions at the time
    • Structural basis of compartment-specific function unknown
  5. 1994 High

    Showed the DNA pairing (paranemic joint) activity is independent of exonuclease activity, separating the two biochemical functions.

    Evidence Filter binding, EM, and in vitro pairing with exonuclease controls

    PMID:7926736

    Open questions at the time
    • Physiological role of DNA pairing in vivo unresolved
  6. 1995 High

    Localized Xrn1 predominantly to the cytoplasm and quantified its high abundance, anchoring its primary role in cytoplasmic RNA metabolism.

    Evidence Cell fractionation, immunofluorescence, and quantitative immunoblot in yeast

    PMID:7739553

    Open questions at the time
    • Nuclear pool function not characterized
  7. 1995 High

    Placed XRN1 and the SKI complex in parallel pathways controlling fate of degradation-targeted transcripts via synthetic lethality and a G1/Start arrest.

    Evidence Genetic epistasis and synthetic lethality in yeast double mutants

    PMID:7739552

    Open questions at the time
    • Molecular basis of the parallel pathway relationship not defined
  8. 1995 High

    Demonstrated a microtubule-associated activity, showing Xrn1 promotes tubulin polymerization and supports spindle/karyogamy functions in yeast.

    Evidence In vitro tubulin polymerization, co-sedimentation, and genetic interaction with tubulin genes

    PMID:7720696

    Open questions at the time
    • Whether microtubule role is conserved beyond yeast unknown
    • Relationship to nuclease activity unclear
  9. 1995 Medium

    Mapped the essential, conserved N-terminal region of Xrn1 versus a dispensable C-terminus, beginning structure–function dissection.

    Evidence N- and C-terminal deletion complementation in yeast

    PMID:8529461

    Open questions at the time
    • Specific catalytic residues not yet identified
    • Single-lab deletion analysis
  10. 1995 High

    Connected XRN1-mediated decay to meiotic double-strand break repair through a recombination pathway parallel to Rad51/Dmc1.

    Evidence EM of meiotic spreads, physical recombination assays, and genetic epistasis

    PMID:7713413

    Open questions at the time
    • Direct mechanism of Xrn1 in DSB repair unresolved
  11. 1997 High

    Defined the biochemical sensitivity of Xrn1 to 5'-proximal secondary structure and oligo(G) tracts, a property later central to viral evasion.

    Evidence In vitro exoribonuclease assays with structured RNA substrates and PABP competition

    PMID:9207242

    Open questions at the time
    • Structural basis of stalling not yet visualized
  12. 1998 Medium

    Confirmed conservation by localizing human XRN1 (hSEP1) to the cytoplasm.

    Evidence Subcellular fractionation and Western blot of human cells

    PMID:9802570

    Open questions at the time
    • Human substrate repertoire not addressed
    • Single study
  13. 2000 Medium

    Linked XRN1 decay function to capping and cap-recognition machinery through synthetic lethality with eIF4E and guanylyltransferase mutants.

    Evidence Synthetic lethality and high-copy suppression in yeast

    PMID:10790382

    Open questions at the time
    • Direct physical coupling to cap complex not shown here
  14. 2003 Medium

    Extended XRN1 function to development, showing the 5'→3' decay pathway is required for epithelial morphogenesis.

    Evidence RNAi knockdown of xrn-1 in C. elegans embryos

    PMID:14681585

    Open questions at the time
    • Target mRNAs driving the morphogenesis defect unknown
    • RNAi-only evidence
  15. 2005 High

    Identified XRN1 as the nuclease degrading the 3' products of RISC/siRNA-directed cleavage, integrating it into the RNAi pathway.

    Evidence RNAi depletion of XRN1 vs exosome in Drosophila S2 cells with intermediate detection

    PMID:15703439

    Open questions at the time
    • Recruitment to RISC products not defined
  16. 2008 High

    Showed XRN1 participates in rapid tRNA decay of hypomodified tRNAs, broadening its substrate range beyond mRNA.

    Evidence Genetic deletions in trm8Δ trm4Δ strains with tRNA stability and aminoacylation assays

    PMID:18443146

    Open questions at the time
    • How hypomodified tRNAs become XRN1 substrates mechanistically unclear
  17. 2008 High

    Established 5'-end RNA secondary structure as the molecular basis of XRN1 resistance using a narnavirus model.

    Evidence XRN1 overexpression/deletion and mutational analysis of viral 5' stem in yeast

    PMID:18640978

    Open questions at the time
    • High-resolution structure of the stalling element not determined here
  18. 2010 High

    Defined the flaviviral xrRNA principle: a 3' UTR pseudoknot stalls XRN1 to generate sfRNA, the first defined RNA element that halts the processive enzyme.

    Evidence In vitro degradation with purified XRN1, structure probing, mutagenesis, and heterologous sfRNA production

    PMID:20739539

    Open questions at the time
    • Atomic structure of stalled XRN1–xrRNA complex not resolved
  19. 2011 High

    Solved the catalytic mechanism: structures revealed 5'-monophosphate recognition by a basic pocket and aromatic stacking driving processivity and coupled duplex melting.

    Evidence X-ray crystallography of Xrn1–substrate plus mutagenesis and processivity assays

    PMID:21297639 PMID:21362555

    Open questions at the time
    • Conformational dynamics during processive translocation not captured
    • Partner-binding platform interactions inferred structurally but not all validated
  20. 2011 Medium

    Showed viral host-shutoff (KSHV SOX) recruits XRN1 to translating mRNAs, linking endonucleolytic cleavage to XRN1 degradation during translation.

    Evidence Polysome sedimentation and XRN1 depletion with cleavage-intermediate detection

    PMID:22046136

    Open questions at the time
    • Direct XRN1–ribosome contact not yet structurally shown at this stage
  21. 2012 High

    Identified the direct decapping–decay coupling: an XRN1 DCP1-binding motif engages DCP1/EDC4 to hand off decapped mRNAs.

    Evidence Co-IP and NMR structure of DCP1 EVH1–XRN1 DBM in fly and human cells

    PMID:23142987

    Open questions at the time
    • Stoichiometry and dynamics of the handoff in vivo not fully defined
  22. 2012 High

    Established that flaviviral sfRNA represses XRN1 to globally stabilize host mRNAs during infection.

    Evidence sfRNA-null mutant virus with XRN1 activity and mRNA stability measurements

    PMID:23006624

    Open questions at the time
    • Quantitative impact on specific host transcripts not delineated
  23. 2012 High

    Showed miR-122 protects HCV RNA specifically from XRN1-mediated 5' decay, defining XRN1 as a major restriction nuclease antagonized by a host miRNA.

    Evidence siRNA knockdown, miR-122 supplementation, and decay-intermediate sequencing in infected cells

    PMID:23248316

    Open questions at the time
    • Mechanism of miR-122 5'-end shielding not structurally defined
  24. 2012 High

    Identified Dcs1 as an essential cofactor that activates Xrn1 by improving RNA affinity, required for respiratory growth.

    Evidence In vitro reconstitution with purified Xrn1/Dcs1, co-IP, and in vivo growth assays

    PMID:22570495

    Open questions at the time
    • Structural basis of Dcs1 activation not resolved
    • Whether a mammalian equivalent exists not addressed
  25. 2013 High

    Demonstrated Xrn1 is specifically required for the global mRNA buffering that couples decay rates to transcription, revealing a decay-to-synthesis feedback role.

    Evidence Comparative dynamic transcriptome analysis across 46 yeast decay mutants

    PMID:24119399

    Open questions at the time
    • Molecular signal transmitting decay status to transcription unknown
  26. 2014 High

    Resolved the dengue xrRNA architecture, showing XRN1 stalls at a three-way-junction fold after processively degrading ~10 kb.

    Evidence Real-time in vitro XRN1 resistance assays, mutagenesis, and cell-based sfRNA detection

    PMID:24692447

    Open questions at the time
    • Generality across all flaviviral xrRNAs not established here
  27. 2015 High

    Defined XRN1 as a regulator of endogenous dsRNA and dsRNA-responsive innate immunity, since its depletion activates PKR and OAS/RNase L.

    Evidence siRNA depletion in vaccinia-infected cells with dsRNA and pathway activation assays

    PMID:25766294

    Open questions at the time
    • Source of accumulating dsRNA not identified at this stage
  28. 2015 Medium

    Revealed neuronal synaptic XRN1 bodies coupling XRN1 to activity-dependent local translational repression.

    Evidence Imaging in primary neurons with synaptic stimulation and XRN1 knockdown

    PMID:25736288

    Open questions at the time
    • Target mRNAs and decay vs sequestration roles in SX-bodies unclear
    • Single lab
  29. 2015 High

    Connected Pacman/XRN1 to apoptosis by targeting pro-apoptotic hid and reaper mRNAs for degradation in Drosophila.

    Evidence Null mutant, rescue by pro-apoptotic gene deletion, and pre-mRNA/mRNA quantification

    PMID:25836675

    Open questions at the time
    • Whether mammalian XRN1 regulates apoptotic transcripts similarly not addressed
  30. 2015 Medium

    Showed glucose-regulated eisosome sequestration of Xrn1 inhibits its decay activity, defining a reversible spatial control mechanism.

    Evidence Live-cell imaging of GFP-Xrn1 with PIL1/SUR7 deletion and glucose addition

    PMID:25811606

    Open questions at the time
    • Signal triggering eisosome recruitment not defined
    • Single lab
  31. 2017 High

    Mapped the Pat1–Xrn1 interaction via a helical leucine-rich motif shared with Dcp2, integrating Xrn1 into the decapping-activator network.

    Evidence Crystallography of Pat1–HLM, co-IP, and in vivo mRNA decay assays

    PMID:29078363

    Open questions at the time
    • Competition between HLM partners in vivo not quantified
  32. 2017 Medium

    Confirmed eisosome-sequestered Xrn1 is enzymatically intact and reactivated by glucose, establishing sequestration as a storage rather than degradation mechanism.

    Evidence mRNA decay assays in wild-type and pil1Δ strains with glucose addition

    PMID:28501103

    Open questions at the time
    • Physiological advantage of sequestration not quantified
    • Single lab
  33. 2017 Medium

    Showed Xrn1 physically engages totivirus Gag and is under positive selection, defining a species-specific antiviral arms race.

    Evidence Co-IP of Xrn1–Gag, phylogenetic selection analysis, and cross-species complementation

    PMID:27711183

    Open questions at the time
    • Functional consequence of Gag binding on Xrn1 activity unclear
    • Single lab
  34. 2017 Medium

    Extended XRN1-stalling RNA elements to bunyaviral/arenaviral structures, including a candidate G-quadruplex.

    Evidence In vitro XRN1 stalling assays with viral substrates and mutagenesis

    PMID:29118186

    Open questions at the time
    • G-quadruplex mechanism not confirmed structurally
    • Single lab
  35. 2017 Medium

    Implicated Xrn1 in telomere homeostasis, promoting checkpoint activation, Cdc13 loading, and Rif1 transcript downregulation.

    Evidence Genetic deletion with telomere length, checkpoint, ChIP, and RNA assays

    PMID:28160602

    Open questions at the time
    • Whether telomere roles depend on RNA decay activity not fully separated
    • Single lab
  36. 2018 High

    Defined the YTHDC2–XRN1 interaction through ankyrin repeats, recruiting XRN1 to m6A-marked mRNAs for degradation.

    Evidence RNA-independent co-IP, domain mapping, and CRAC analysis

    PMID:29970596

    Open questions at the time
    • In vivo extent of m6A-directed XRN1 decay not quantified
  37. 2018 Medium

    Showed the DNA damage kinase Rad53 phosphorylates Xrn1, linking decay to checkpoint signaling, though intrinsic nuclease activity was unchanged in vitro.

    Evidence Phosphoproteomic screen and in vitro kinase plus nuclease assays

    PMID:30377154

    Open questions at the time
    • In vivo functional consequence of phosphorylation not established
    • Phosphosites' effect on specificity untested
  38. 2018 Medium

    Established XRN1 as a post-transcriptional negative regulator of autophagy via its ribonuclease activity in yeast and mammals.

    Evidence Chromosomal deletion, catalytic mutant analysis, and siRNA depletion with autophagy assays

    PMID:29465287

    Open questions at the time
    • Direct ATG transcript targeting mechanism not fully defined
    • Single lab
  39. 2019 High

    Provided the structural basis for co-translational decay by visualizing Xrn1 docked at the ribosomal mRNA exit site ~17 nt from the decoding center.

    Evidence Cryo-EM of programmed 80S ribosome–Xrn1 complex

    PMID:30911188

    Open questions at the time
    • How Xrn1 couples to ribosome speed/quality control not resolved
  40. 2019 High

    Mapped the low-complexity CIR region of human XRN1 as a direct binder and inhibitor of CCR4-NOT and PatL1, coupling deadenylation to decay.

    Evidence In vitro deadenylase assays with purified proteins and reporter decay in XRN1-null complementation

    PMID:31340047

    Open questions at the time
    • Physiological role of CIR-mediated deadenylase inhibition in vivo unclear
  41. 2019 Medium

    Revealed a positive role for Xrn1 in translation and ER localization of a subset of membrane-protein mRNAs, coupling synthesis, translation, and decay.

    Evidence Ribosome profiling, polysome analysis, ER fractionation, and interaction studies

    PMID:30899024

    Open questions at the time
    • Mechanism distinguishing stimulatory from degradative roles unclear
    • Single lab
  42. 2020 Medium

    Extended Xrn1's gene-expression coupling to transcription, showing it modulates Pol II initiation and elongation as an activator.

    Evidence NET-seq and transcription rate modeling in xrn1Δ yeast

    PMID:32518159

    Open questions at the time
    • Direct mechanism connecting cytoplasmic Xrn1 to nuclear Pol II unknown
    • Single lab
  43. 2021 High

    Identified a separable deNADding activity by which Xrn1 removes intact NAD caps from RNAs, required for non-fermentative growth.

    Evidence In vitro NAD-cap decapping with a separation-of-function mutant and growth/mitochondrial RNA analysis

    PMID:35173156

    Open questions at the time
    • Whether deNADding occurs in mammalian XRN1 not addressed here
  44. 2021 Medium

    Showed measles virus relocalizes XRN1 to inclusion bodies to degrade dsRNA and suppress the PKR-ISR pathway, aiding replication.

    Evidence Immunofluorescence localization, XRN1 knockout, dsRNA and PKR phosphorylation assays

    PMID:36300942

    Open questions at the time
    • Mechanism of XRN1 translocation to inclusion bodies unclear
    • Single lab
  45. 2021 Medium

    Showed influenza NS1 directly binds XRN1, which suppresses RIG-I-mediated IFN-β, defining a viral co-option of XRN1's immune-dampening role.

    Evidence Co-IP, co-localization, knockdown/overexpression, and IFN-β/p-IRF3 assays

    PMID:34311580

    Open questions at the time
    • Whether NS1 alters XRN1 catalytic activity unclear
    • Single lab
  46. 2022 High

    Demonstrated XRN1 enhances the YTHDC2 3'→5' helicase activity essential for fertility, integrating XRN1 into germ-cell mitotic-to-meiotic transition control.

    Evidence In vitro helicase reconstitution with XRN1 plus mouse and zebrafish genetic models

    PMID:35305312

    Open questions at the time
    • Mechanism by which XRN1 stimulates helicase activity unresolved
  47. 2023 High

    Showed the EDC4–XRN1 interaction controls decapping flux and P-body homeostasis, with disruption stabilizing miRNA-targeted mRNAs and enlarging P-bodies.

    Evidence Interaction-disrupting mutants, reporter decay, P-body/stress-granule imaging, and null-cell complementation

    PMID:37621215

    Open questions at the time
    • How XRN1 stoichiometry sets P-body size mechanistically unclear
  48. 2024 Medium

    Established that XRN1 prevents accumulation of endogenous Alu-derived cytosolic dsRNA, defining XRN1 dependency in ISG-high cancers via PKR and RIG-I/MAVS.

    Evidence CRISPR deletion, dsRNA quantification, pathway epistasis, drug rescue, and pan-cancer screen analysis

    PMID:38261511 PMID:38261514

    Open questions at the time
    • Precise endogenous dsRNA species driving PKR vs MAVS not fully resolved
    • Therapeutic window in tumors untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How XRN1's many context-specific roles—co-translational decay, decay-transcription buffering, deNADding, dsRNA surveillance, and partner-directed recruitment—are integrated and differentially regulated in human cells remains unresolved.
  • No structure of the human ribosome–XRN1 complex
  • Regulation of XRN1 partner choice (DCP1/EDC4 vs CCR4-NOT vs YTHDC2) in vivo not defined
  • In vivo significance of Rad53 phosphorylation and mammalian cofactor equivalents of Dcs1 unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 8 GO:0003723 RNA binding 3 GO:0016787 hydrolase activity 3 GO:0003677 DNA binding 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1 GO:0005840 ribosome 1
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 1

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 XRN1 encodes a 5'→3' exoribonuclease in yeast; disruption of the gene is not lethal but markedly reduces cell growth rate, which is rescued by reintroduction of XRN1 on a plasmid. Gene disruption (knockout) in haploid yeast, complementation with plasmid-borne XRN1, poly(A) hydrolytic activity assay, immunoreactivity Gene High 1979303
1992 XRN1 (also known as DST2/SEP1/KEM1/RAR5) encodes a 160-kDa 5'→3' exoribonuclease; xrn1-deleted yeast cells show 2–4-fold longer half-lives of specific short-lived mRNAs, increased cellular protein levels, and reduced rRNA synthesis rate, demonstrating XRN1's key role in mRNA turnover. Gene sequencing, gene disruption, Northern analysis of specific mRNA half-lives, metabolic labeling, PAGE analysis Gene High 1398123
1991 The SEP1 (XRN1) protein promotes homologous DNA pairing (strand exchange) in vitro and is required in meiosis; sep1 mutants show reduced meiotic recombination and defective sporulation, with arrest after commitment to recombination but before meiosis I. Gene cloning, protein overproduction and purification, in vitro strand exchange assay, mutant phenotype analysis (sporulation, recombination) Molecular and cellular biology High 1840632
1993 XRN1/KEM1 encodes the major cytoplasmic 5'→3' exoribonuclease (p175); its essential nuclear paralog HKE1/RAT1 encodes a related 5'→3' exoribonuclease (p116); overexpression of XRN1 p175 cannot rescue loss of HKE1/RAT1, indicating non-redundant functions. Gene cloning, in vitro 5'→3' exoribonuclease activity assay, immunodepletion, complementation test Molecular and cellular biology High 8417335
1994 Sep1 (XRN1) promotes paranemic joint formation between homologous DNA molecules in vitro; the pairing does not require net intertwining and requires as little as 41 bp of homology; the exonuclease activity of Sep1 is not responsible for the joint. Nitrocellulose filter binding assay, electron microscopy, in vitro DNA pairing with defined substrates, exonuclease activity controls Genes & development High 7926736
1995 Sep1/Xrn1 is an abundant cytoplasmic protein (~80,000 molecules/diploid cell); >90% is cytoplasmic by cell fractionation and indirect immunofluorescence, supporting a role in cytoplasmic RNA metabolism rather than nuclear processes. Cell fractionation, indirect immunofluorescence, quantitative immunoblot Molecular and cellular biology High 7739553
1995 sep1 (xrn1) ski2 and sep1 (xrn1) ski3 double mutants are synthetically lethal in a manner independent of killer viruses, and sep1 ski2/ski3 double mutants arrest in late G1 at Start; this places XRN1 and the SKI complex in parallel pathways controlling translation on transcripts targeted for degradation. Genetic epistasis, synthetic lethality screen, temperature-sensitive allele analysis, cell cycle arrest characterization Molecular and cellular biology High 7739552
1995 Sep1/Xrn1 promotes polymerization of porcine brain and yeast tubulin into microtubules in vitro and co-sediments with microtubules; sep1 mutants show increased benomyl sensitivity, chromosome loss, karyogamy defect, and impaired spindle pole body separation; genetic interaction with tubulin genes supports a role as a microtubule-associated protein. In vitro tubulin polymerization assay, sucrose cushion co-sedimentation, benomyl sensitivity assay, genetic double mutants with tubulin genes The EMBO journal High 7720696
1995 N-terminal sequences of Sep1/Xrn1 are essential for complementing slow growth and benomyl hypersensitivity, while at least 270 C-terminal amino acids are dispensable; the essential sequences correspond to regions conserved with the S. pombe Exo2 homolog. N- and C-terminal deletion analysis, plasmid complementation of null mutant Chromosoma Medium 8529461
1995 sep1 mutants arrest in pachytene during meiotic prophase with normal synaptonemal complex; the arrest is RAD9-independent; sep1 is deficient in meiotic double-strand break repair, and sep1 dmc1 and sep1 rad51 double mutants virtually eliminate pop-out recombination, indicating parallel recombination pathways. Electron microscopy of meiotic spreads, physical assay of recombination intermediates, genetic epistasis with rad51/dmc1 Genetics High 7713413
1997 XRN1 5'→3' exoribonucleolytic hydrolysis is stalled by oligo(G) tracts and strong secondary structures in RNA; poly(A) binding protein inhibits XRN1 hydrolysis of poly(A) but does not affect the related HKE1; stem-loop structures near the 5' end cause greater inhibition of HKE1 than XRN1. In vitro 5'→3' exoribonuclease assay with defined RNA substrates containing secondary structures, protein competition experiments Biochemical and biophysical research communications High 9207242
1998 Human XRN1 (hSEP1) protein is localized in the cytoplasm, as determined by cytochemical analysis and Western blot of fractionated cellular extracts. Subcellular fractionation, Western blot, cytochemical analysis DNA research Medium 9802570
2000 Genetic synthetic lethality between xrn1Δ and cdc33 (eIF4E) or ceg1 (guanylyltransferase) mutations indicates that XRN1-mediated mRNA turnover pathway is functionally linked to proper mRNA capping and eIF4E–eIF4G interaction; blocking XRN1 enhances the requirement for 7mG caps and cap-recognition complex. Synthetic lethality screen, genetic epistasis, high-copy suppression analysis Genetics Medium 10790382
2004 The C. elegans 5'→3' exoribonuclease xrn-1 is required for ventral epithelial enclosure during embryogenesis; RNAi knockdown of xrn-1 results in failure of epithelial closure, establishing a role for the 5'→3' mRNA decay pathway in morphogenesis. RNAi knockdown of xrn-1 in C. elegans, embryonic phenotype analysis RNA (New York, N.Y.) Medium 14681585
2005 In Drosophila cells, 3' mRNA fragments generated by RISC cleavage are degraded from their 5' ends by XRN1, while 5' fragments are degraded by the exosome; this establishes XRN1 as the nuclease responsible for degrading the 3' products of siRNA-directed cleavage. RNAi depletion of XRN1 and exosome components in Drosophila S2 cells, RNA blot detection of RISC cleavage intermediates RNA (New York, N.Y.) High 15703439
2008 XRN1 (along with Rat1) is a component of the rapid tRNA decay (RTD) pathway that degrades hypomodified mature tRNA species in yeast; deletion of XRN1 and RAT1 prevents both degradation and deacylation of hypomodified tRNA(Val(AAC)) and rescues temperature-sensitive growth. Genetic deletion of XRN1, RAT1, and MET22 in trm8Δ trm4Δ strains, Northern blot for tRNA levels, aminoacylation assays, growth phenotype analysis Genes & development High 18443146
2008 The 20S RNA narnavirus 5'-end strong secondary structure (G-rich, buried stem) enables it to evade SKI1/XRN1-mediated degradation; mutations that weaken this structure make the virus vulnerable to XRN1, demonstrating that RNA secondary structure at the 5' end is the molecular basis of XRN1 resistance. XRN1 overexpression and deletion in yeast, mutational analysis of viral 5'-stem structure, viral copy number measurement The Journal of biological chemistry High 18640978
2010 An RNA pseudoknot (PSK3) in the yellow fever virus 3' UTR is required for stalling the host XRN1 exonuclease and producing sfRNA; the pseudoknot was confirmed by structure probing and mutagenesis; the stalling element alone is sufficient to direct sfRNA-like RNA production from a heterologous vector. In vitro XRN1 degradation assay with purified XRN1, RNA structure probing, mutagenesis, 5' end sequencing of sfRNA, heterologous expression Journal of virology High 20739539
2011 Crystal structure of Xrn1 in complex with a substrate reveals that the 5'-terminal trinucleotide stacks between aromatic side chains while a highly basic pocket specifically recognizes the 5' phosphate; mutations in residues binding the 5'-terminal nucleotide impair Xrn1 processivity; the mechanism couples processive hydrolysis to duplex melting for substrates with single-stranded 5' overhangs. X-ray crystallography of Xrn1–substrate complex, site-directed mutagenesis of binding residues, in vitro processivity and activity assays Molecular cell High 21362555
2011 Crystal structure of Kluyveromyces lactis Xrn1 (residues 1–1245, E178Q mutant) shows that the two conserved XRN regions form the active site, and that a unique 510-residue segment (absent from Rat1/Xrn2) contains four domains (D1–D4) that stabilize the N-terminal segment conformation and likely serve as a platform for protein partners; mutagenesis confirms functional importance of D1–D4 for activity. X-ray crystallography, site-directed mutagenesis, in vitro biochemical activity assays Nature structural & molecular biology High 21297639
2011 XRN1 is recruited to translating mRNAs following SOX-induced internal cleavage by the Kaposi's sarcoma-associated herpesvirus host shutoff factor, and degrades the resulting fragments; SOX co-sediments with translation initiation complexes and cleaved intermediates accumulate in the 40S fraction, indicating XRN1 degrades mRNAs during translation. Polysome sedimentation, RNA blot detection of cleavage intermediates, XRN1 depletion, co-sedimentation analysis PLoS pathogens Medium 22046136
2012 XRN1 directly interacts with DCP1 in Drosophila cells and with EDC4 in human cells, coupling mRNA decapping to 5'→3' degradation; the interaction is mediated by the DCP1 EVH1 domain binding a DCP1-binding motif (DBM) in XRN1's C-terminal region, as revealed by NMR structure. Co-immunoprecipitation, NMR structure of DCP1 EVH1 domain bound to XRN1 DBM peptide, in vivo interaction mapping Nature structural & molecular biology High 23142987
2012 Flavivirus sfRNA formation inhibits XRN1 activity in Dengue- and Kunjin virus-infected cells; XRN1 repression results in accumulation of uncapped mRNAs and increased overall cellular mRNA stability; a mutant Kunjin virus unable to form sfRNA does not affect host mRNA stability or XRN1 activity. Viral infection with sfRNA-null mutant virus, sfRNA expression in absence of infection, XRN1 activity assays, mRNA stability measurements, detection of uncapped mRNA intermediates RNA (New York, N.Y.) High 23006624
2012 HCV RNA replication is degraded primarily by XRN1 in infected cells; XRN1 knockdown enhances HCV replication and miR-122 supplementation and XRN1 knockdown have equal, redundant, nonadditive effects on viral RNA decay, indicating miR-122 protects HCV RNA specifically from XRN1-mediated 5' decay. XRN1 siRNA knockdown, miR-122 supplementation, viral RNA decay assays, sequencing of 5' and 3' RNA degradation intermediates in infected cells Proceedings of the National Academy of Sciences of the United States of America High 23248316
2012 Dcs1 (scavenger decapping enzyme) functions as a specific cofactor of Xrn1 in yeast: Dcs1 improves the apparent affinity of Xrn1 for RNA and forms a complex with Xrn1 in vitro; Xrn1 is essentially inactive in the absence of Dcs1 in vivo; this activation is required for mitochondrial respiration (growth on glycerol). In vitro RNA binding and exoribonuclease assays with purified proteins, co-IP, in vivo growth assays, 2D protein gel analysis of deletion strains Proceedings of the National Academy of Sciences of the United States of America High 22570495
2013 Global mRNA level buffering in yeast requires Xrn1: in strains lacking mRNA degradation factors, changes in degradation rates are compensated by changes in synthesis rates, but this buffering is abolished in xrn1Δ strains, indicating Xrn1 is required for the feedback coupling between mRNA decay and transcription. Comparative dynamic transcriptome analysis (cDTA) with metabolic RNA labeling in 46 yeast mutant strains Molecular cell High 24119399
2014 Dengue virus sfRNA is produced by XRN1 loading at the 5' end of genomic RNA and processively degrading ~10 kb, stalling at two independently-folded RNA structures organized around a three-way junction; disrupting the junction's fold eliminates sfRNA production in human cells infected with flavivirus. Real-time in vitro XRN1 resistance assay, RNA mutagenesis, RNA folding analysis, cell-based sfRNA detection in flavivirus-infected human cells eLife High 24692447
2015 XRN1 depletion in vaccinia virus-infected cells leads to accumulation of double-stranded RNA (dsRNA) and activation of PKR and OAS/RNase L innate immune effectors; XRN1 is therefore a cellular factor regulating dsRNA accumulation and dsRNA-responsive innate immunity, and is required for VacV growth. siRNA depletion of XRN1 in VacV-infected cells, dsRNA quantification, PKR and OAS pathway activation assays, viral growth assays Cell host & microbe High 25766294
2015 XRN1 co-localizes with post-synaptic structures in neurons as discrete 'synaptic XRN1 bodies' (SX-bodies) distinct from P-bodies or stress granules; NMDA receptor stimulation increases SX-body size and number while decreasing local translation, and XRN1 knockdown impairs NMDA-triggered translational repression. Fluorescence microscopy in primary neurons, XRN1 siRNA knockdown, synaptic stimulation assays (NMDA, mGluR), local translation measurements Journal of cell science Medium 25736288
2015 In Drosophila, null mutation in pacman/xrn1 increases expression of pro-apoptotic mRNAs hid and reaper at the post-transcriptional level; the null phenotype (small imaginal discs, pupal lethality) is rescued by deletion removing one copy of reaper/hid/grim, placing Pacman/XRN1 in the apoptotic pathway by targeting these mRNAs for degradation. Drosophila genetic null mutation, rescue by pro-apoptotic gene deletion, quantitative RT-PCR of hid and reaper mRNAs, pre-mRNA analysis to confirm post-transcriptional regulation Biology open High 25836675
2015 Xrn1 accumulates at plasma membrane-associated eisosomes after glucose exhaustion (post-diauxic shift) in yeast, dependent on eisosome components Pil1 and Sur7; this sequestration is not accompanied by other mRNA-decay machinery components and Xrn1 is released from eisosomes by glucose addition. Fluorescence microscopy of GFP-tagged Xrn1, genetic deletion of PIL1 and SUR7, glucose addition experiments PloS one Medium 25811606
2017 Yeast Pat1 C-terminal region directly interacts with a helical leucine-rich motif (HLM) in the C-terminal region of yeast Xrn1, as revealed by structural analysis of Pat1-HLM complexes; this interaction surface also recruits Dcp2, and ability to bind HLMs is required for efficient growth and normal mRNA decay. Co-immunoprecipitation, X-ray crystallography of Pat1-HLM complex, in vivo mRNA decay assays, growth assays Proceedings of the National Academy of Sciences of the United States of America High 29078363
2017 Xrn1 sequestration at eisosomes during post-diauxic shift in yeast inhibits Xrn1-mediated mRNA degradation; eisosome-associated Xrn1 retains its enzymatic functionality and is re-activated upon glucose addition; cells lacking eisosome organizer Pil1 retain Xrn1 mRNA decay activity into stationary phase. mRNA decay assays in wild-type and pil1Δ strains, glucose addition experiments, Xrn1 localization tracking European journal of cell biology Medium 28501103
2017 Xrn1 physically interacts with the Gag protein of the L-A totivirus in S. cerevisiae, and XRN1 has evolved under positive natural selection in Saccharomyces with sequence differences that translate to species-specific antiviral activity against cognate L-A viruses. Co-immunoprecipitation of Xrn1 with L-A Gag protein, phylogenetic analysis of positive selection, cross-species complementation experiments with different Xrn1 orthologs PLoS pathogens Medium 27711183
2017 RNA structures in the 3'-terminal portion of the Rift Valley fever virus N mRNA and in ambisense transcripts of arenaviruses can stall and repress XRN1; the phlebovirus stalling element likely forms a G-quadruplex structure. In vitro XRN1 stalling biochemical assays, mutagenesis, G-quadruplex prediction The Journal of biological chemistry Medium 29118186
2017 Xrn1 promotes ssDNA generation at uncapped telomeres and is necessary for DNA damage checkpoint activation upon telomere uncapping; Xrn1 also maintains telomere length by promoting Cdc13 association with telomeres independently of ssDNA generation, and downregulates the Rif1 telomerase-inhibitor transcript. Genetic deletion of XRN1, telomere length assays, checkpoint activation assays, ChIP for Cdc13 association, RNA levels analysis Nucleic acids research Medium 28160602
2018 The m6A reader YTHDC2 directly interacts with XRN1 via its ankyrin repeat domains in an RNA-independent manner; this interaction recruits XRN1 to m6A-containing mRNAs, promoting their degradation, while the YTH and R3H domains of YTHDC2 also contribute to RNA binding. Co-immunoprecipitation (RNA-independent conditions), domain mapping (ankyrin repeat deletions), CRAC analysis, YTH domain binding assay RNA (New York, N.Y.) High 29970596
2018 The DNA damage checkpoint kinase Rad53 directly phosphorylates Xrn1 in vitro; Xrn1 was the most enriched substrate in a phosphoproteomic screen for Rad53 targets; phosphorylation of Xrn1 by Rad53 does not affect Xrn1's intrinsic nuclease activity in vitro but may affect activity or specificity in vivo. Mass spectrometry-based phosphoproteomic screen, in vitro kinase assay with Rad53 and Xrn1, in vitro nuclease activity assay G3 (Bethesda, Md.) Medium 30377154
2018 XRN1 is a post-transcriptional negative regulator of autophagy in both yeast and mammalian cells; XRN1 deletion in yeast enhances autophagy and upregulates ATG transcripts via its ribonuclease activity; in mammalian cells, XRN1 siRNA depletion enhances autophagy and picornavirus replication. Chromosomal deletion of XRN1, autophagy assays (autophagosome formation), ATG transcript level measurement, catalytic mutant analysis, siRNA depletion in mammalian cells Autophagy Medium 29465287
2019 Cryo-EM structure of the S. cerevisiae 80S ribosome–Xrn1 complex reveals that Xrn1 binds at the mRNA exit site of the ribosome via its conserved core; mRNA is channelled directly from the ribosomal decoding site into the Xrn1 active center, separated by only 17 ± 1 nucleotides, enabling co-translational mRNA decay. Cryo-electron microscopy structure determination of programmed 80S ribosome–Xrn1 complex Nature structural & molecular biology High 30911188
2019 A low-complexity C-terminal region of human XRN1 (CIR) directly interacts with the CCR4-NOT deadenylase complex and with the decapping activator PatL1; CIR overexpression represses reporter mRNA deadenylation in human cells and inhibits CCR4-NOT and CAF1 deadenylase activity in vitro; PatL1 binding to CIR alleviates CIR-mediated inhibition of CCR4-NOT. In vitro deadenylase activity assay with purified proteins, reporter mRNA deadenylation assay in XRN1-null cell line complementation, direct binding assays Nucleic acids research High 31340047
2019 Xrn1 promotes translation of a specific group of transcripts encoding membrane proteins via interactions with components of the translation initiation machinery and correlates with Xrn1-dependence for mRNA localization at the endoplasmic reticulum; for this group, Xrn1 stimulates transcription, mRNA translation, and decay. Transcriptome-wide ribosome profiling, polysome analysis, ER fractionation, biochemical interaction studies with translation initiation factors Nature communications Medium 30899024
2019 Xrn1 modulates RNA polymerase II (Pol II) transcription initiation and elongation; NET-seq in xrn1Δ yeast shows reduced Pol II occupancy downstream of transcription start sites and increased Pol II accumulation near cleavage/polyadenylation sites with features of backtracked Pol II; Xrn1 functions mainly as a transcriptional activator. Native elongating transcript sequencing (NET-seq), mathematical modeling of transcription rates in xrn1Δ yeast The Journal of biological chemistry Medium 32518159
2020 Xrn1 biochemically associates with eisosomal proteins specifically after the post-diauxic shift in yeast but not during exponential growth; decapping complex and Lsm1-7/Pat1 complex do not associate with eisosomal proteins under the same conditions, indicating selective sequestration of Xrn1. Tandem affinity purification (TAP) and mass spectrometry in different growth phases, biochemical co-purification microPublication biology Medium 37746059
2021 Xrn1 is a NAD cap decapping (deNADding) enzyme: it releases intact NAD from NAD-capped RNAs and subsequently degrades the RNA; a deNADding-deficient Xrn1 mutant that retains 5'-monophosphate exonuclease activity reveals that Xrn1 deNADding is required for normal growth on non-fermenting sugar and modulates mitochondrial NAD-capped RNA levels. In vitro NAD cap decapping assay with Xrn1, deNADding-deficient point mutant generation, growth phenotype analysis on glycerol, mitochondrial RNA fractionation and analysis Nature communications High 35173156
2021 Measles virus (MeV) hijacks XRN1 by translocating it to cytoplasmic inclusion bodies (IBs) where viral replication occurs; XRN1 at IBs degrades dsRNA, suppressing PKR-ISR pathway activation and facilitating viral replication; XRN1 knockout increases dsRNA accumulation, PKR activation, and suppresses MeV replication. Immunofluorescence localization of XRN1 in MeV-infected cells, XRN1 knockout, dsRNA immunofluorescence, PKR phosphorylation assays, viral replication assays Journal of virology Medium 36300942
2021 XRN1 directly interacts with NS1 protein of influenza A virus (IAV) and co-localizes with NS1 in P-bodies; XRN1 suppresses RIG-I-mediated IFN-β production; XRN1 depletion impairs viral replication and enhances innate immune response, while overexpression increases viral titers. Co-immunoprecipitation of XRN1 and NS1, co-localization immunofluorescence, XRN1 knockdown/knockout and overexpression, IFN-β mRNA and p-IRF3 quantification, viral titer assays mBio Medium 34311580
2022 The 3'→5' RNA helicase activity of YTHDC2 is essential for mouse fertility; this helicase activity is enhanced by YTHDC2's interaction with XRN1; loss of helicase activity (catalytic-dead mutant, dominant negative) causes infertility with mixed mitotic/meiotic transcriptome identity in germ cells. Mouse genetic knockin of catalytic-dead YTHDC2 helicase mutation, biochemical in vitro helicase assay with and without XRN1, single-cell transcriptomics, zebrafish ythdc2 mutant analysis Molecular cell High 35305312
2023 Disrupting the EDC4–XRN1 interaction or altering their stoichiometry in human cells inhibits mRNA decapping and stabilizes microRNA-targeted mRNAs in a translationally repressed state; this leads to larger P-bodies that prevent mRNA decapping; P-bodies support cell viability and prevent stress granule formation when XRN1 is limiting. Disruption of EDC4-XRN1 interaction (domain mutants), reporter mRNA decay assays, P-body size/number quantification by microscopy, stress granule formation assay, XRN1-null cell line complementation The EMBO journal High 37621215
2024 XRN1 depletion activates the dsRNA sensor RIG-I/MAVS pathway and IFN signaling by causing accumulation of cytosolic dsRNA from endogenous retroelements (Alus); XRN1 is an essential gene for survival of a subset of cancer cells with high ISG expression, and this dependency is mediated by PKR and MAVS signaling. CRISPR-based XRN1 deletion in cancer cell lines, dsRNA quantification, RIG-I/MAVS knockdown epistasis, pan-cancer CRISPR screen analysis, dsRNA-inducing drug combination Cell reports Medium 38261511
2024 XRN1 deletion causes PKR pathway activation and cancer cell lethality in cells with high interferon-stimulated gene (ISG) expression; XRN1 depletion causes accumulation of endogenous complementary sense/anti-sense RNAs as candidate PKR ligands; JAK1/2 inhibition (reducing PKR levels) rescues sensitivity to XRN1 deletion. XRN1 CRISPR deletion, PKR pathway activation assays, ruxolitinib rescue experiment, IFN-β stimulation sensitization experiment, endogenous dsRNA sequencing Cell reports Medium 38261514

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast. Nature 289 21697827
2005 Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome. RNA (New York, N.Y.) 265 15703439
2008 Degradation of several hypomodified mature tRNA species in Saccharomyces cerevisiae is mediated by Met22 and the 5'-3' exonucleases Rat1 and Xrn1. Genes & development 223 18443146
2018 The m6A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5'-3' exoribonuclease XRN1. RNA (New York, N.Y.) 212 29970596
2013 Global analysis of eukaryotic mRNA degradation reveals Xrn1-dependent buffering of transcript levels. Molecular cell 202 24119399
2012 Competing and noncompeting activities of miR-122 and the 5' exonuclease Xrn1 in regulation of hepatitis C virus replication. Proceedings of the National Academy of Sciences of the United States of America 184 23248316
2014 RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA. eLife 177 24692447
2012 A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability. RNA (New York, N.Y.) 172 23006624
2011 Coupled 5' nucleotide recognition and processivity in Xrn1-mediated mRNA decay. Molecular cell 162 21362555
2012 A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5' exonucleolytic degradation. Nature structural & molecular biology 142 23142987
2010 An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1. Journal of virology 139 20739539
1992 Characterization of the XRN1 gene encoding a 5'-->3' exoribonuclease: sequence data and analysis of disparate protein and mRNA levels of gene-disrupted yeast cells. Gene 123 1398123
1990 Disruption of the gene XRN1, coding for a 5'----3' exoribonuclease, restricts yeast cell growth. Gene 120 1979303
1993 An essential yeast gene with homology to the exonuclease-encoding XRN1/KEM1 gene also encodes a protein with exoribonuclease activity. Molecular and cellular biology 104 8417335
2011 Structural and biochemical studies of the 5'→3' exoribonuclease Xrn1. Nature structural & molecular biology 99 21297639
1991 Molecular and genetic analysis of the gene encoding the Saccharomyces cerevisiae strand exchange protein Sep1. Molecular and cellular biology 98 1840632
2015 Cellular 5'-3' mRNA exonuclease Xrn1 controls double-stranded RNA accumulation and anti-viral responses. Cell host & microbe 92 25766294
2012 The 5' → 3' exoribonuclease XRN1/Pacman and its functions in cellular processes and development. Wiley interdisciplinary reviews. RNA 92 22383165
1995 Synthetic lethality of sep1 (xrn1) ski2 and sep1 (xrn1) ski3 mutants of Saccharomyces cerevisiae is independent of killer virus and suggests a general role for these genes in translation control. Molecular and cellular biology 82 7739552
2015 New hypotheses derived from the structure of a flaviviral Xrn1-resistant RNA: Conservation, folding, and host adaptation. RNA biology 78 26399159
2011 Coordinated destruction of cellular messages in translation complexes by the gammaherpesvirus host shutoff factor and the mammalian exonuclease Xrn1. PLoS pathogens 76 22046136
1995 Regulation and intracellular localization of Saccharomyces cerevisiae strand exchange protein 1 (Sep1/Xrn1/Kem1), a multifunctional exonuclease. Molecular and cellular biology 74 7739553
2022 The XRN1-regulated RNA helicase activity of YTHDC2 ensures mouse fertility independently of m6A recognition. Molecular cell 69 35305312
2015 Regulation of Hepatitis C Virus Genome Replication by Xrn1 and MicroRNA-122 Binding to Individual Sites in the 5' Untranslated Region. Journal of virology 67 25855736
2019 Structure of the 80S ribosome-Xrn1 nuclease complex. Nature structural & molecular biology 66 30911188
2015 XRN1 stalling in the 5' UTR of Hepatitis C virus and Bovine Viral Diarrhea virus is associated with dysregulated host mRNA stability. PLoS pathogens 66 25747802
2015 Dissecting the roles of the 5' exoribonucleases Xrn1 and Xrn2 in restricting hepatitis C virus replication. Journal of virology 58 25673723
1995 A role of Sep1 (= Kem1, Xrn1) as a microtubule-associated protein in Saccharomyces cerevisiae. The EMBO journal 53 7720696
2016 A novel serine protease, Sep1, from Bacillus firmus DS-1 has nematicidal activity and degrades multiple intestinal-associated nematode proteins. Scientific reports 46 27118554
1997 sep1+ encodes a transcription-factor homologue of the HNF-3/forkhead DNA-binding-domain family in Schizosaccharomyces pombe. Gene 46 9427538
2015 A dual yet opposite growth-regulating function of miR-204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrine-like prostate cancer cells. Oncotarget 45 25797256
2004 The 5'-3' exoribonuclease xrn-1 is essential for ventral epithelial enclosure during C. elegans embryogenesis. RNA (New York, N.Y.) 43 14681585
2018 Wolbachia-mediated virus blocking in mosquito cells is dependent on XRN1-mediated viral RNA degradation and influenced by viral replication rate. PLoS pathogens 42 29494679
2017 A unique surface on Pat1 C-terminal domain directly interacts with Dcp2 decapping enzyme and Xrn1 5'-3' mRNA exonuclease in yeast. Proceedings of the National Academy of Sciences of the United States of America 42 29078363
1995 The sep1 mutant of Saccharomyces cerevisiae arrests in pachytene and is deficient in meiotic recombination. Genetics 42 7713413
2019 The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins. Nature communications 41 30899024
2016 XRN1 Is a Species-Specific Virus Restriction Factor in Yeasts. PLoS pathogens 41 27711183
1997 Structural modifications of RNA influence the 5' exoribonucleolytic hydrolysis by XRN1 and HKE1 of Saccharomyces cerevisiae. Biochemical and biophysical research communications 41 9207242
2021 Pseudoknot length modulates the folding, conformational dynamics, and robustness of Xrn1 resistance of flaviviral xrRNAs. Nature communications 37 34741027
2008 20S RNA narnavirus defies the antiviral activity of SKI1/XRN1 in Saccharomyces cerevisiae. The Journal of biological chemistry 37 18640978
2018 The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy. Autophagy 35 29465287
2023 The EDC4-XRN1 interaction controls P-body dynamics to link mRNA decapping with decay. The EMBO journal 34 37621215
2000 The S. pombe sep1 gene encodes a nuclear protein that is required for periodic expression of the cdc15 gene. FEBS letters 33 10996305
1999 Deletion of the sep1(+) forkhead transcription factor homologue is not lethal but causes hyphal growth in Schizosaccharomyces pombe. Biochemical and biophysical research communications 33 10491317
2019 A low-complexity region in human XRN1 directly recruits deadenylation and decapping factors in 5'-3' messenger RNA decay. Nucleic acids research 32 31340047
2017 Rapid decay of engulfed extracellular miRNA by XRN1 exonuclease promotes transient epithelial-mesenchymal transition. Nucleic acids research 32 27994032
2015 Evolutionarily conserved 5'-3' exoribonuclease Xrn1 accumulates at plasma membrane-associated eisosomes in post-diauxic yeast. PloS one 29 25811606
2016 The roles of the exoribonucleases DIS3L2 and XRN1 in human disease. Biochemical Society transactions 28 27911720
1996 Requirement of S. pombe exonuclease II, a homologue of S. cerevisiae Sep1, for normal mitotic growth and viability. Current genetics 28 8781170
2022 Xrn1 is a deNADding enzyme modulating mitochondrial NAD-capped RNA. Nature communications 27 35173156
2016 Interrogating the degradation pathways of unstable mRNAs with XRN1-resistant sequences. Nature communications 27 27917860
2012 Activation of 5'-3' exoribonuclease Xrn1 by cofactor Dcs1 is essential for mitochondrial function in yeast. Proceedings of the National Academy of Sciences of the United States of America 27 22570495
2015 Synaptic control of mRNA translation by reversible assembly of XRN1 bodies. Journal of cell science 26 25736288
2020 Spatio-temporal characterization of the antiviral activity of the XRN1-DCP1/2 aggregation against cytoplasmic RNA viruses to prevent cell death. Cell death and differentiation 23 32034313
2019 The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4. Nucleic acids research 23 31392315
2017 Identification of phlebovirus and arenavirus RNA sequences that stall and repress the exoribonuclease XRN1. The Journal of biological chemistry 23 29118186
2003 mRNA decay: x (XRN1) marks the spot. Molecular cell 23 12769838
2018 The Yeast DNA Damage Checkpoint Kinase Rad53 Targets the Exoribonuclease, Xrn1. G3 (Bethesda, Md.) 22 30377154
2017 mRNA decay is regulated via sequestration of the conserved 5'-3' exoribonuclease Xrn1 at eisosome in yeast. European journal of cell biology 22 28501103
2020 The yeast exoribonuclease Xrn1 and associated factors modulate RNA polymerase II processivity in 5' and 3' gene regions. The Journal of biological chemistry 21 32518159
2013 The 5'-3' exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNA miR-277-3p in Drosophila wing imaginal discs. RNA biology 21 23792537
2019 Structural features of an Xrn1-resistant plant virus RNA. RNA biology 20 30951405
2015 Xrn1/Pacman affects apoptosis and regulates expression of hid and reaper. Biology open 20 25836675
2002 The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma. Gene 20 12426100
2024 Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer. Cell reports 19 38261511
2021 Cellular 5'-3' mRNA Exoribonuclease XRN1 Inhibits Interferon Beta Activation and Facilitates Influenza A Virus Replication. mBio 19 34311580
2021 Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence. Scientific reports 18 34611223
1995 Identification of functional domains in the Sep1 protein (= Kem1, Xrn1), which is required for transition through meiotic prophase in Saccharomyces cerevisiae. Chromosoma 18 8529461
1994 The Sep1 strand exchange protein from Saccharomyces cerevisiae promotes a paranemic joint between homologous DNA molecules. Genes & development 17 7926736
2023 Targeting RNA Exonuclease XRN1 Potentiates Efficacy of Cancer Immunotherapy. Cancer research 16 36638333
2019 Detection and quantification of RNA decay intermediates using XRN1-resistant reporter transcripts. Nature protocols 15 31019309
2012 XRN1: A Major 5' to 3' Exoribonuclease in Eukaryotic Cells. The Enzymes 15 27166442
2019 XRN1-associated long non-coding RNAs may contribute to fungal virulence and sexual development in entomopathogenic fungus Cordyceps militaris. Pest management science 14 31025499
2024 XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells. Cell reports 13 38261514
2020 Biochemical Characterization of Yeast Xrn1. Biochemistry 13 32251580
2015 RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1. Nucleic acids research 13 26656493
2012 Novel interaction of two clock-relevant RNA-binding proteins C3 and XRN1 in Chlamydomonas reinhardtii. FEBS letters 13 23068615
2020 Xrn1 influence on gene transcription results from the combination of general effects on elongating RNA pol II and gene-specific chromatin configuration. RNA biology 12 33138675
2000 Inhibition of mRNA turnover in yeast by an xrn1 mutation enhances the requirement for eIF4E binding to eIF4G and for proper capping of transcripts by Ceg1p. Genetics 12 10790382
2022 Host 5'-3' Exoribonuclease XRN1 Acts as a Proviral Factor for Measles Virus Replication by Downregulating the dsRNA-Activated Kinase PKR. Journal of virology 11 36300942
2017 Immunohistochemical localization of exoribonucleases (DIS3L2 and XRN1) in intranuclear inclusion body disease. Neuroscience letters 11 29100804
2021 Processing of RNA Containing 8-Oxo-7,8-Dihydroguanosine (8-oxoG) by the Exoribonuclease Xrn-1. Frontiers in molecular biosciences 10 34869601
2020 Xrn1-resistant RNA structures are well-conserved within the genus flavivirus. RNA biology 10 33064973
2003 Trypsin/alpha-amylase inhibitors inactivate the endogenous barley/malt serine endoproteinase SEP-1. Journal of agricultural and food chemistry 10 12952437
2021 Zinc Finger Protein ZFP36L1 Inhibits Flavivirus Infection by both 5'-3' XRN1 and 3'-5' RNA-Exosome RNA Decay Pathways. Journal of virology 9 34643435
2021 Neuronal XRN1 is required for maintenance of whole-body metabolic homeostasis. iScience 9 34646989
1997 Cloning and characterization of mouse Dhm2 cDNA, a functional homolog of budding yeast SEP1. Gene 9 9218715
2023 The RNA helicases Dbp2 and Mtr4 regulate the expression of Xrn1-sensitive long non-coding RNAs in yeast. Frontiers in RNA research 8 37667796
2021 All genera of Flaviviridae host a conserved Xrn1-resistant RNA motif. RNA biology 8 33858294
1995 Use of monoclonal antibodies in the functional characterization of the Saccharomyces cerevisiae Sep1 protein. European journal of biochemistry 8 7543408
2021 Solid-phase XRN1 reactions for RNA cleavage: application in single-molecule sequencing. Nucleic acids research 7 33511416
2021 A plant-infecting subviral RNA associated with poleroviruses produces a subgenomic RNA which resists exonuclease XRN1 in vitro. Virology 7 34808564
2020 Recruitment of Xrn1 to stress-induced genes allows efficient transcription by controlling RNA polymerase II backtracking. RNA biology 6 33258404
2017 Regulation of telomere metabolism by the RNA processing protein Xrn1. Nucleic acids research 6 28160602
2021 sORF-Encoded Polypeptide SEP1 Is a Novel Virulence Factor of Phytophthora Pathogens. Molecular plant-microbe interactions : MPMI 5 33103962
1998 Cloning and characterization of human Sep1 (hSEP1) gene and cytoplasmic localization of its product. DNA research : an international journal for rapid publication of reports on genes and genomes 5 9802570
2023 Xrn1 biochemically associates with eisosome proteins after the post diauxic shift in yeast. microPublication biology 4 37746059
2023 Xrn1-resistant RNA motifs are disseminated throughout the RNA virome and are able to block scanning ribosomes. Scientific reports 4 37749116
2020 Effects of 5'-3' Exonuclease Xrn1 on Cell Size, Proliferation and Division, and mRNA Levels of Periodic Genes in Cryptococcus neoformans. Genes 4 32316250
2025 The zinc finger protein ZFP36L2 inhibits flavivirus infection via the 5'-3' XRN1-mediated RNA decay pathway in the replication complexes. Journal of biomedical science 3 39972499

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