Affinage

ISG20

Interferon-stimulated gene 20 kDa protein · UniProt Q96AZ6

Length
181 aa
Mass
20.4 kDa
Annotated
2026-06-13
56 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ISG20 is an interferon-inducible 3'-5' exoribonuclease that restricts a broad spectrum of RNA viruses and shapes the innate immune response (PMID:11401564, PMID:12594219). Biochemically it is a DEDDh-family exonuclease that degrades single-stranded RNA far more efficiently than DNA, using Mn2+ as cofactor; its crystal structure places it in the DEDDh group with active-site residues Met14 and Arg53 contacting the substrate ribose 2'-OH to confer RNA preference (PMID:11401564, PMID:15527770). Its antiviral activity against RNA viruses including VSV, influenza, EMCV, HIV-1, HCV and bunyaviruses requires intact exonuclease activity (PMID:12594219, PMID:16033969, PMID:21036379, PMID:29695422). ISG20 achieves restriction through several routes: direct, structure-guided degradation of viral RNA, exemplified by binding to the HBV epsilon stem-loop via its C-terminal ExoIII domain and degradation of HBV transcripts (PMID:28399146); translational inhibition of non-self RNAs that correlates with localization to cytoplasmic P-bodies and spares endogenous transcripts (PMID:31600344); and indirect amplification of the IFN program by upregulating downstream ISGs such as IFIT1 to suppress viral translation (PMID:30232164, PMID:41511982). Substrate fate is tuned by epitranscriptomic marks: m6A modification recruits YTHDF2 to promote degradation of HBV RNA, whereas YTHDF1 binding to m6A on the EBOV genome antagonizes ISG20, and 2'O-methylation blocks degradation through steric clash with residues R53 and D90 (PMID:32059034, PMID:36354007, PMID:41423124). Cellular mRNAs are protected primarily by PABP1 loading on their poly(A) tails (PMID:38418089). ISG20 transcription is driven by a unique ISRE acting through IRF-1 for both type I and type II IFN, and by NF-κB in response to dsRNA (PMID:10871365, PMID:15064705). Beyond viral defense, ISG20 participates in nuclear RNA quality control of spliceosomal U snRNAs and degrades specific cellular mRNAs (RHOBTB3, STAT1, IRF1) to modulate the tumor immune microenvironment in triple-negative breast cancer (PMID:33147372, PMID:41385111).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2000 High

    Established how ISG20 expression is wired into the IFN response, defining the transcriptional logic that makes it an effector of both type I and type II IFN.

    Evidence Promoter dissection, reporter assays and EMSA for Sp-1, USF-1 and IRF-1 in cells

    PMID:10871365

    Open questions at the time
    • Did not address ISG20 protein function or enzymatic role
    • Did not link the ISRE to any specific antiviral outcome
  2. 2001 High

    Defined ISG20 as an enzyme by reconstituting 3'-5' exonuclease activity with a strong preference for ssRNA over ssDNA, identifying its biochemical substrate.

    Evidence In vitro exonuclease assays with purified protein, metal and pH optimization

    PMID:11401564

    Open questions at the time
    • No cellular substrate identified
    • No structural basis for RNA preference
  3. 2003 High

    Connected the enzymatic activity to a biological role by showing exonuclease-dependent restriction of RNA but not DNA viruses, establishing ISG20 as an antiviral effector.

    Evidence Overexpression of WT and active-site-dead ISG20 in HeLa cells with VSV/influenza/EMCV/adenovirus infection

    PMID:12594219

    Open questions at the time
    • Did not show direct degradation of viral RNA in cells
    • Mechanism of viral RNA selectivity unknown
  4. 2004 High

    Resolved the structural basis of RNA substrate preference, placing ISG20 in the DEDDh family and identifying ribose-contacting residues.

    Evidence X-ray crystallography at 1.9 Å with Mn2+ and UMP plus comparison to DNase homologs

    PMID:15527770

    Open questions at the time
    • No structure with a longer RNA or viral substrate
    • Did not address how modifications affect catalysis
  5. 2004 Medium

    Showed a second induction pathway via dsRNA-driven NF-κB then IRF-1, with distinct subcellular consequences, broadening the contexts that mobilize ISG20.

    Evidence Reporter assays, EMSA and fractionation comparing poly I:C versus IFN induction

    PMID:15064705

    Open questions at the time
    • Single lab
    • Functional consequence of nuclear matrix enrichment not defined
  6. 2006 Medium

    Mapped endogenous ISG20 to nucleolar and Cajal body compartments and to snRNP/snoRNA machinery, hinting at a role beyond viral defense.

    Evidence Immunofluorescence, EM, SMN co-IP and RNA-IP for U snRNAs/U3 snoRNA

    PMID:16514659

    Open questions at the time
    • Functional consequence of snRNA association not tested
    • Did not establish whether localization is required for antiviral activity
  7. 2010 Medium

    Extended exonuclease-dependent restriction to multiple positive-strand RNA viruses in a cell-type-specific manner and established paralog specificity.

    Evidence Ectopic expression with active-site mutant across HCV, BVDV, HAV, YFV, SARS-CoV and ISG20L1/L2 controls

    PMID:21036379

    Open questions at the time
    • Basis of cell-type specificity unknown
    • No direct viral RNA degradation demonstrated
  8. 2016 Medium

    Identified influenza nucleoprotein as a viral interaction partner and linked ISG20 to impaired viral polymerase function.

    Evidence Co-IP and co-localization of ISG20 with IAV NP, polymerase activity assays, active-site mutant

    PMID:27342813

    Open questions at the time
    • Single Co-IP context; NP interaction inferred to depend on activity
    • Direct vs indirect effect on polymerase not separated
  9. 2017 High

    Provided the clearest case of direct, structure-guided substrate recognition by mapping ISG20 binding to the HBV epsilon stem-loop via its ExoIII domain and revealing a degradation-independent restriction mode.

    Evidence EMSA direct binding, ExoIII deletion, epsilon structure mutants, catalytic-dead ISG20D94G encapsidation assays

    PMID:28399146

    Open questions at the time
    • Generality of stem-loop recognition to other viruses untested
    • No co-structure of ISG20 bound to epsilon
  10. 2018 Medium

    Revealed an indirect antiviral mechanism for alphaviruses in which ISG20 amplifies ISGs like IFIT1 rather than degrading viral RNA, diversifying its mode of action.

    Evidence Inducible expression, RNA-seq, negative viral RNA degradation assay, Isg20-/- mice

    PMID:30232164

    Open questions at the time
    • Mechanism by which ISG20 upregulates ISGs unknown
    • Single lab
  11. 2018 Medium

    Confirmed RNase-dependent antibunyaviral activity through a functional ISG screen and mapped viral sequence determinants of sensitivity.

    Evidence ISG-expression flow cytometry screen, minigenome/VLP assays, active-site mutant, in vitro viral evolution

    PMID:29695422

    Open questions at the time
    • Why phleboviruses escape unresolved
    • Direct degradation of bunyaviral RNA not shown
  12. 2019 High

    Defined a translational-inhibition mechanism distinct from degradation, localized to P-bodies and based on self/non-self RNA discrimination, with KO mice confirming physiological relevance.

    Evidence Ribosome/translation assays, negative RNA stability assays, P-body live imaging, Isg20-/- mice, murine ortholog

    PMID:31600344

    Open questions at the time
    • Molecular basis of self/non-self discrimination at P-bodies incomplete
    • Relationship between translational control and exonuclease activity not fully resolved
  13. 2020 High

    Identified the m6A-YTHDF2 axis as a cofactor system directing ISG20 to m6A-modified HBV RNA, linking epitranscriptomics to substrate selection.

    Evidence Catalytic-dead ISG20D94G co-IP of YTHDF2 and m6A RNA, methyltransferase/YTHDF2 knockdowns, HBV m6A site mutants, decay assays

    PMID:32059034

    Open questions at the time
    • Whether YTHDF2 directs ISG20 to non-HBV substrates not addressed
    • Structural basis of the ternary complex unknown
  14. 2020 Medium

    Implicated ISG20 in nuclear RNA quality control of spliceosomal U snRNA precursors alongside the nuclear exosome, supporting a housekeeping function.

    Evidence In vitro 3'-end maturation assay, ISG20 and exosome knockdown, U1 snRNA 3'-end sequencing

    PMID:33147372

    Open questions at the time
    • Relative contribution of ISG20 vs exosome unclear
    • Link to antiviral role not established
  15. 2021 Medium

    Extended ISG20 activity to deaminated HBV cccDNA, identifying it as the nuclease mediating IFN-induced cccDNA loss in cooperation with APOBEC3A.

    Evidence ISG20 depletion/co-expression, nucleolar localization, deoxyuridine-ssDNA enrichment, cccDNA quantification

    PMID:33969602

    Open questions at the time
    • Direct nuclease action on cccDNA versus indirect effects not fully separated
    • Single lab
  16. 2023 High

    Established that 2'O-methylation blocks ISG20 by steric clash at R53/D90, explaining how host RNA marks and viral RNA modification status govern degradation susceptibility.

    Evidence In vitro degradation of 2'O-methylated substrates, R53/D90 mutagenesis, FTSJ3-KO hypomethylated HIV-1, T-cell infection

    PMID:36354007

    Open questions at the time
    • In vivo contribution of 2'O-methylation evasion to viral fitness untested
    • Interplay with m6A-directed degradation not integrated
  17. 2023 Medium

    Revealed a pro-tumor function in which ISG20 degrades specific cellular mRNAs (RHOBTB3, STAT1, IRF1) to remodel the immune microenvironment, extending its substrate repertoire to host transcripts.

    Evidence ISG20 KD/OE in TNBC, mRNA decay assays, HIF-1α/NANOG/CXCL10 readouts, anti-PD1 mouse model

    PMID:41385111

    Open questions at the time
    • Selectivity rules for these mRNAs versus protected transcripts unclear
    • Single lab
  18. 2024 Medium

    Defined how cellular mRNAs evade ISG20, showing PABP1 poly(A) loading and stable 3' stem-loops provide protection, completing the self/non-self discrimination model.

    Evidence RNA-seq, biochemical PABP1 loading assays, stem-loop stability analysis, histone mRNA quantification

    PMID:38418089

    Open questions at the time
    • How viral RNAs avoid equivalent protection not fully resolved
    • Single lab
  19. 2025 Medium

    Showed that m6A can also antagonize ISG20 via YTHDF1 on the EBOV genome, demonstrating that the same mark can promote or block degradation depending on the reader.

    Evidence EBOV m6A mapping, ISG20/YTHDF1 knockdown, m6A site mutants, co-IP, replication assays

    PMID:41423124

    Open questions at the time
    • Mechanism distinguishing YTHDF1 antagonism from YTHDF2 promotion unclear
    • Single lab
  20. 2026 Medium

    Demonstrated indirect restriction of DNA herpesviruses through IFN signaling amplification, confirmed by JAK-STAT inhibition rescue, reinforcing the non-degradative arm of ISG20 action.

    Evidence OE/KD, RNA-seq, negative viral RNA/DNA half-life assays, ruxolitinib rescue, scRNA-seq

    PMID:41511982

    Open questions at the time
    • Molecular trigger by which ISG20 amplifies IFN unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ISG20 integrates its multiple modes (direct degradation, translational inhibition, ISG amplification) and what determines which mode operates for a given target remains unresolved.
  • No unified model linking substrate features, localization and mechanism choice
  • No structure of ISG20 engaging a modified or structured viral RNA
  • Mechanism by which catalytic-independent ISG amplification occurs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0003723 RNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 2 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 3
Partners
IAV NPPABP1YTHDF1YTHDF2
Complex memberships
SMN complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 ISG20/HEM45 protein functions as a 3' to 5' exonuclease in vitro, displaying a pH optimum of ~7.0, preferring Mn2+ as a metal cofactor, and degrading single-stranded RNA at a rate approximately 35-fold higher than single-stranded DNA. In vitro biochemical exonuclease assay with purified protein; metal cofactor and pH optimization experiments Biochemistry High 11401564
2004 Crystal structure of human ISG20 at 1.9 Å resolution reveals it complexed with two Mn2+ ions and UMP; it belongs to the DEDDh group of RNases and its active site is structurally similar to DNases (E. coli DNA Pol III ε subunit and Exo I). Distinctive residues Met14 and Arg53 form hydrogen bonds with the 2'-OH of the UMP ribose, likely conferring RNA substrate preference. X-ray crystallography at 1.9 Å with Mn2+ and UMP ligands; structural comparison with homologs FEBS letters High 15527770
2000 The ISG20 promoter lacks TATA and CAAT elements; basal transcriptional activity depends on Sp-1 and USF-1. A unique ISRE mediates both type I and type II IFN induction strictly dependent on IRF-1, and this ISRE also contributes to constitutive transcriptional activity. Promoter cloning, deletion analysis, reporter assays, EMSA for Sp-1, USF-1, and IRF-1 binding; dominant-negative and overexpression of transcription factors Nucleic acids research High 10871365
2003 ISG20 exerts antiviral activity against RNA genomic viruses (VSV, influenza, EMCV) but not DNA adenovirus; it specifically inhibits VSV mRNA synthesis and protein production. Antiviral effect requires exonuclease activity, as the exonuclease-inactive mutant has no antiviral effect. The inactive mutant can inhibit ISG20 exonuclease activity in vitro (dominant-negative), and its expression reduces IFN-mediated VSV inhibition. Overexpression of wild-type and exonuclease-inactive ISG20 in HeLa cells; viral infection assays; mRNA and protein synthesis analysis; in vitro exonuclease inhibition by dominant-negative mutant The Journal of biological chemistry High 12594219
2004 ISG20 induction by synthetic dsRNA (poly I:C) is stronger and faster than by IFN. Transcriptional activation of ISG20 by dsRNA involves initial NF-κB (p50/p65) binding to a κB element followed by IRF-1 binding to the ISRE. Contrary to IFN, dsRNA induces nuclear matrix enrichment of ISG20. Reporter assays; EMSA; chromatin-based binding assays; immunofluorescence/subcellular fractionation Oncogene Medium 15064705
2005 ISG20 inhibits HIV-1 replication; antiviral effect requires the exonuclease activity of ISG20, as exonuclease-inactive mutant ISG20 shows no antiviral effect. HIV-1-induced apoptosis is significantly reduced in cells infected with HIV-1 expressing ISG20. HIV-1-derived virus expressing ISG20 (HIV-1NL4-3ISG20); replication kinetics in CEM cells and PBMCs; exonuclease-inactive mutant comparison The Journal of general virology Medium 16033969
2006 Endogenous ISG20 localizes predominantly to the nucleolus (dense fibrillar component, the major site for rRNA processing) and Cajal bodies, in addition to diffuse cytoplasmic and nucleoplasmic distribution. ISG20 is associated with SMN-containing macromolecular nuclear complexes and with U1, U2 snRNAs, and U3 snoRNA. IFN treatment increases ISG20 accumulation in Cajal bodies. Immunofluorescence, electron microscopy, co-immunoprecipitation of SMN complexes, RNA immunoprecipitation for snRNAs/snoRNAs, coilin-dsRed coexpression Journal of cellular biochemistry Medium 16514659
2010 ISG20 inhibits positive-strand RNA viruses including HCV, bovine viral diarrhea virus, hepatitis A virus, and yellow fever virus in a cell-type-specific manner, but not SARS-CoV in Huh7.5 cells. All antiviral effects require exonuclease activity. The closely related paralogs ISG20L1 and ISG20L2 do not inhibit HCV replication. Ectopic overexpression; exonuclease-inactive mutant comparison; viral replication assays across multiple virus families and cell types Virology Medium 21036379
2017 ISG20 inhibits HBV replication by degrading HBV RNA. The susceptibility element was mapped to the HBV RNA terminal redundant region containing the epsilon (ε) stem-loop. ISG20 binds the ε stem-loop directly in vitro in the absence of other cellular proteins (EMSA), with the lower stem portion of ε being the major binding site. The C-terminal ExoIII domain of ISG20 is responsible for ε binding; deletion of ExoIII abolishes in vitro binding and intracellular HBV RNA degradation. Enzymatic-inactive ISG20D94G retains antiviral activity by preventing pgRNA encapsidation via ISG20-ε interaction even without degradation. EMSA (direct binding); ExoIII domain deletion; HBV ε structure mutants; ISG20D94G catalytic mutant; encapsidation assays; cellular HBV RNA decay assays PLoS pathogens High 28399146
2018 ISG20 localizes primarily to Cajal bodies in the nucleus when ectopically expressed. In the context of alphavirus restriction, ISG20 does not directly degrade viral RNAs; instead, it upregulates over 100 other genes including IFIT1, an ISG that suppresses translation of alphavirus RNAs, leading to indirect inhibition of viral RNA translation. Inducible ectopic expression system; Isg20-/- mice; RNA-seq of ISG20-expressing cells; viral RNA degradation assays (negative finding for direct RNA degradation); IFIT1 protein quantification; alphavirus replication assays in wild-type vs Isg20-/- mice mSphere Medium 30232164
2018 ISG20 exhibits potent antibunyaviral activity (Peribunyaviridae, Hantaviridae, Nairoviridae) but phleboviruses largely escape inhibition. Antibunyaviral activity depends on RNase activity. In vitro evolution of resistant BUNV mapped sequence determinants of ISG20 sensitivity/resistance. ISG-expression flow cytometry screen of ~500 ISGs; minigenome/VLP assay; exonuclease-inactive mutant; in vitro viral evolution for resistance mapping Journal of virology Medium 29695422
2019 ISG20 inhibits VSV replication by decreasing viral protein synthesis without degrading viral RNA. ISG20 exerts translational control over non-self RNAs (including those from transfected DNA) while sparing endogenous transcripts. This activity correlates with ISG20's localization in cytoplasmic processing bodies (P-bodies). Murine ISG20 ortholog functions similarly; Isg20-/- mice show increased susceptibility to viral infection. VSV infection assays; ribosome profiling / translation assays; viral RNA stability assays (negative for degradation); subcellular localization by live imaging to P-bodies; Isg20-/- mouse infection model; non-self RNA transfection controls PLoS pathogens High 31600344
2020 m6A-modified HBV transcripts are selectively recognized and degraded by ISG20. The m6A reader protein YTHDF2 acts as a cofactor: ISG20 forms a complex with YTHDF2 and m6A-modified HBV RNA (demonstrated using enzymatically inactive ISG20D94G). Silencing of m6A methyltransferases or YTHDF2 reduces ISG20-mediated HBV RNA degradation. m6A at position A1907 within the ε stem-loops is the critical site. ISG20D94G co-immunoprecipitation of YTHDF2 and m6A RNA; methyltransferase knockdown; YTHDF2 knockdown; HBV m6A site mutants (5', 3', both termini); HBV RNA decay assays PLoS pathogens High 32059034
2021 ISG20 is required for IFN-induced degradation of HBV cccDNA. ISG20 is the only type I and II IFN-induced nuclear protein with annotated nuclease activity. ISG20 localizes to nucleoli of IFN-stimulated hepatocytes and is enriched on deoxyuridine-containing ssDNA mimicking APOBEC3A-deaminated HBV DNA. Co-expression of ISG20 with APOBEC3A is sufficient to diminish cccDNA; ISG20 depletion mitigates IFN-induced cccDNA loss. Transcriptome analysis; ISG20 overexpression and depletion; immunofluorescence localization; enrichment assay on deoxyuridine-ssDNA; APOBEC3A co-expression; HBV cccDNA quantification EMBO reports Medium 33969602
2020 ISG20 promotes degradation of nascent spliceosomal U snRNA transcripts and unstable U1 snRNA variants. ISG20 and the nuclear exosome were biochemically identified as exonucleolytic factors acting on U snRNA precursors in vitro, but KD experiments showed they act in quality control of newly synthesized U snRNAs rather than as maturation factors per se. In vitro 3'-end maturation assay (newly developed); ISG20 and nuclear exosome knockdown; 3'-end sequencing of endogenous U1 snRNA Genes to cells Medium 33147372
2023 RNA 2'O-methylation impedes ISG20-mediated RNA degradation. ISG20 pauses two nucleotides upstream of and at 2'O-methylated residues. Structure-function analysis identified ISG20 residues R53 and D90 as responsible for steric clash with 2'O-methylated nucleotides. Hypomethylated HIV-1 genomes (from FTSJ3-KO cells) are more susceptible to ISG20-mediated degradation in vitro and show impaired reverse transcription in T cells with IFN-induced ISG20. Biochemical RNA degradation assays with 2'O-methylated RNA substrates; site-directed mutagenesis of R53 and D90; FTSJ3-KO cells producing hypomethylated HIV-1; in vitro degradation comparison; T-cell infection assays with IFN Nucleic acids research High 36354007
2016 ISG20 inhibits influenza A virus replication in an exonuclease-dependent manner, impairing viral polymerase activity and reducing replication and transcription of viral genes. ISG20 co-localizes and directly interacts with IAV nucleoprotein (NP); the exonuclease-inactive ISG20 mutant lacks this association, indicating NP interaction depends on ISG20 exonuclease activity. Overexpression and exonuclease-inactive mutant; viral polymerase activity assay; co-localization by immunofluorescence; co-immunoprecipitation of ISG20 with NP; viral titer and protein assays Virus genes Medium 27342813
2023 ISG20 degrades RHOBTB3 mRNA, increasing HIF-1α protein expression and activating NANOG signaling; ISG20 also degrades STAT1 and IRF1 mRNAs, decreasing CXCL10 expression and impairing CD8+ T cell and NK cell recruitment. These functions are downstream of HIF-1-activated ISG20 transcription in TNBC. Silencing ISG20 increases sensitivity of mouse TNBC cells to anti-PD1 immunotherapy. ISG20 KD/OE in TNBC cells; mRNA stability assays for RHOBTB3, STAT1, IRF1; HIF-1α protein measurement; NANOG reporter; CXCL10 and immune cell recruitment assays; anti-PD1 checkpoint blockade in mouse model The Journal of experimental medicine Medium 41385111
2024 Poly(A)-binding protein (PABP1) loading on the RNA 3' tail provides primary protection of cellular mRNAs against ISG20-mediated degradation. Terminal stem-loop RNA structures can also confer protection, depending on their thermodynamic stability. Histone mRNAs (non-polyadenylated, with a 3' stem-loop) show detectable ISG20-mediated decay, consistent with their lack of PABP1 loading. RNA-seq of ISG20-expressing cells; biochemical PABP1 loading assays; stem-loop stability analysis; histone mRNA quantification after ISG20 expression Life science alliance Medium 38418089
2025 m6A modification in the EBOV genome 3'-leader region recruits m6A reader YTHDF1, which impedes ISG20 antiviral activity, thereby facilitating EBOV replication. Loss-of-function and mutational analyses confirm that m6A on the EBOV genome antagonizes ISG20 exonuclease activity. m6A mapping of EBOV genome; loss-of-function (ISG20 and YTHDF1 KD); m6A site mutations in EBOV genome; EBOV replication assays; co-immunoprecipitation of YTHDF1 with m6A-modified RNA and ISG20 International journal of biological macromolecules Medium 41423124
2026 ISG20 inhibits HCMV and HSV-1 replication without degrading viral RNA or DNA; instead, ISG20 expression induces an innate immune defense gene signature comprising upregulation of other ISGs, zinc finger proteins, and transposable elements, amplifying IFN production and response. JAK-STAT inhibitor ruxolitinib rescues HCMV gene expression in ISG20-expressing cells, confirming the indirect mechanism via IFN signaling amplification. Overexpression and knockdown of ISG20; RNA-seq; half-life assays of viral RNA and DNA (negative for direct degradation); ruxolitinib JAK-STAT inhibition rescue experiment; single-cell RNA-seq PLoS pathogens Medium 41511982

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 ISG20, a new interferon-induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses. The Journal of biological chemistry 191 12594219
2017 Interferon-inducible ribonuclease ISG20 inhibits hepatitis B virus replication through directly binding to the epsilon stem-loop structure of viral RNA. PLoS pathogens 118 28399146
2020 Interferon-stimulated gene 20 (ISG20) selectively degrades N6-methyladenosine modified Hepatitis B Virus transcripts. PLoS pathogens 116 32059034
2001 The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro. Biochemistry 97 11401564
2010 Antiviral activities of ISG20 in positive-strand RNA virus infections. Virology 84 21036379
2005 Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1. The Journal of general virology 83 16033969
2018 Lnc-ISG20 Inhibits Influenza A Virus Replication by Enhancing ISG20 Expression. Journal of virology 78 29899085
2000 A unique ISRE, in the TATA-less human Isg20 promoter, confers IRF-1-mediated responsiveness to both interferon type I and type II. Nucleic acids research 73 10871365
2018 The Interferon-Induced Exonuclease ISG20 Exerts Antiviral Activity through Upregulation of Type I Interferon Response Proteins. mSphere 63 30232164
2007 ISG20, an actor of the innate immune response. Biochimie 57 17445960
2021 Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20. EMBO reports 55 33969602
2019 The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation. PLoS pathogens 55 31600344
2022 ISG20: an enigmatic antiviral RNase targeting multiple viruses. FEBS open bio 54 35174977
2004 Crystal structure of human ISG20, an interferon-induced antiviral ribonuclease. FEBS letters 53 15527770
2016 Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein. Virus genes 49 27342813
2018 Interferon-Stimulated Gene (ISG)-Expression Screening Reveals the Specific Antibunyaviral Activity of ISG20. Journal of virology 46 29695422
2020 ISG20 serves as a potential biomarker and drives tumor progression in clear cell renal cell carcinoma. Aging 43 32003757
2004 The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-kappaB and IRF1 activation. Oncogene 41 15064705
2016 Interferon-stimulated gene of 20 kDa protein (ISG20) degrades RNA of hepatitis B virus to impede the replication of HBV in vitro and in vivo. Oncotarget 37 27626689
1998 Expression and estrogen regulation of the HEM45 MRNA in human tumor lines and in the rat uterus. The Journal of steroid biochemistry and molecular biology 36 9569007
2021 LncRNA lnc-ISG20 promotes renal fibrosis in diabetic nephropathy by inducing AKT phosphorylation through miR-486-5p/NFAT5. Journal of cellular and molecular medicine 35 33939247
2017 Interferon-stimulated gene 20-kDa protein (ISG20) in infection and disease: Review and outlook. Intractable & rare diseases research 32 28357179
2006 The exonuclease ISG20 mainly localizes in the nucleolus and the Cajal (Coiled) bodies and is associated with nuclear SMN protein-containing complexes. Journal of cellular biochemistry 32 16514659
2024 TGF β1 promotes the polarization of M2-type macrophages and activates PI3K/mTOR signaling pathway by inhibiting ISG20 to sensitize ovarian cancer to cisplatin. International immunopharmacology 24 38761779
2023 Internal RNA 2'O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect. Nucleic acids research 24 36354007
2021 Disruption of STAT5A and NMI signaling axis leads to ISG20-driven metastatic mammary tumors. Oncogenesis 24 34078871
2009 Prevention of embryo loss in non-obese diabetic mice using adoptive ITGA2(+)ISG20(+) natural killer-cell transfer. Reproduction (Cambridge, England) 22 19321657
2023 ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer. Frontiers in immunology 21 37342328
2023 Targeting RNA oxidation by ISG20-mediated degradation is a potential therapeutic strategy for acute kidney injury. Molecular therapy : the journal of the American Society of Gene Therapy 18 37452495
2008 Cloning, eukaryotic expression of human ISG20 and preliminary study on the effect of its anti-HBV. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 16 18278447
2023 Expression of interferon-stimulated gene 20 (ISG20), an antiviral effector protein, in glomerular endothelial cells: possible involvement of ISG20 in lupus nephritis. Renal failure 13 37340981
2024 FOSL2-mediated transcription of ISG20 induces M2 polarization of macrophages and enhances tumorigenic ability of glioblastoma cells. Journal of neuro-oncology 12 39073688
2013 Differential expression of ISG20 in chronic hepatitis B patients and relation to interferon-alpha therapy response. Journal of medical virology 12 23794439
2017 Estradiol and proinflammatory cytokines stimulate ISG20 expression in synovial fibroblasts of patients with osteoarthritis. Intractable & rare diseases research 11 29259855
2022 ISG20 inhibits bluetongue virus replication. Virologica Sinica 10 35513266
2020 ISG20 is overexpressed in clinically relevant radioresistant oral cancer cells. International journal of clinical and experimental pathology 10 32782682
2022 The regulation of ISG20 expression on SARS-CoV-2 infection in cancer patients and healthy individuals. Frontiers in immunology 8 36177004
2021 Establishment of a Rapid Detection System for ISG20-Dependent SARS-CoV-2 Subreplicon RNA Degradation Induced by Interferon-α. International journal of molecular sciences 8 34769072
2024 The PTPRZ1-MET/STAT3/ISG20 axis in glioma stem-like cells modulates tumor-associated macrophage polarization. Cellular signalling 7 38685521
2024 Stable structures or PABP1 loading protects cellular and viral RNAs against ISG20-mediated decay. Life science alliance 6 38418089
2020 ISG20 and nuclear exosome promote destabilization of nascent transcripts for spliceosomal U snRNAs and U1 variants. Genes to cells : devoted to molecular & cellular mechanisms 5 33147372
2025 Not all RNAs are created equal for the antiviral RNase ISG20. Trends in microbiology 4 39971662
2025 Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKD. Redox biology 3 40644925
2023 Characterization of the induction kinetics and antiviral functions of IRF1, ISG15 and ISG20 in cells infected with gammacoronavirus avian infectious bronchitis virus. Virology 3 37058744
2013 [Antiviral activities of ISG20 against hepatitis C virus]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 3 23663760
2017 A conjugate protein containing HIV TAT, ISG20, and a PRRSV polymerase binding inhibits PRRSV replication and may be a novel therapeutic platform. Research in veterinary science 2 28818749
2025 HIF-1-mediated ISG20 expression promotes breast cancer stemness and immune evasion. The Journal of experimental medicine 1 41385111
2025 Causal inference of CLEC5A and ISG20 in atherosclerosis: integrating Mendelian randomization and eQTL evidence. Frontiers in immunology 1 41415292
2025 Therapeutic potential of ISG20 in attenuating podocyte injury via inhibition of ferroptosis. Molecular therapy. Nucleic acids 1 41583555
2026 Exonuclease ISG20 inhibits human cytomegalovirus replication by inducing an innate immune defense signature. PLoS pathogens 0 41511982
2025 Structural features, transcriptional profiles, and potential roles in antiviral immunity of interferon-stimulated 20-kDa exonuclease (ISG20) in red-spotted grouper (Epinephelus akaara). Fish & shellfish immunology 0 40484065
2025 Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis. PloS one 0 40622935
2025 ISG20: The multifaceted 'molecular star' in cancer research (Review). Oncology reports 0 40937574
2025 ISG20 Restricts BK Polyomavirus Infection and Engages in Reciprocal Regulation with Viral Large T Antigen. Microorganisms 0 41304224
2025 m6A modification in the 3'‑leader region of EBOV genome antagonizes ISG20 to facilitate viral replication. International journal of biological macromolecules 0 41423124
2023 Correction: The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation. PLoS pathogens 0 36795687

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