Affinage

RNASET2

Ribonuclease T2 · UniProt O00584

Length
256 aa
Mass
29.5 kDa
Annotated
2026-06-10
62 papers in source corpus 28 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNASET2 is an evolutionarily conserved acidic endoribonuclease that degrades RNA in multiple subcellular compartments and underpins both intracellular RNA homeostasis and a set of catalysis-independent extracellular signaling functions (PMID:16620762, PMID:15809705). As an enzyme, it is a glycosylated, secreted RNase that localizes to lysosomes (PMID:16620762) and functions as an effector of lysosomal RNA degradation; its loss causes accumulation of undigested rRNA within neuronal lysosomes, defining RNASET2-deficient cystic leukoencephalopathy as a lysosomal storage disorder with rRNA as the storage substrate (PMID:21199949). A distinct pool resides in the mitochondrial intermembrane space, where it degrades mitochondrial RNA and outer-membrane-associated cytosolic rRNAs, feeding back on nuclear rRNA transcription and translation (PMID:28730546, PMID:30385512). This catalytic activity is required for lipotoxic/oxidative-stress-mediated cell death (PMID:26206090) but is dispensable for RNASET2's tumor- and metastasis-suppressive and antiangiogenic activities, which instead depend on actin binding: catalytically inactive and N-terminally truncated forms retain actin-binding, antiangiogenic, and antitumorigenic activity (PMID:15809705, PMID:17109444, PMID:25426551). Secreted RNASET2 acts non-cell-autonomously to remodel the tumor and tissue microenvironment, suppressing Src signaling through altered ECM interaction (PMID:30813308), recruiting monocyte/macrophages and driving M1 polarization with downstream CD8+ T cell expansion and tumor rejection (PMID:21189302, PMID:32197460), and entering recipient cells via the mannose receptor to bind SLK and activate N-WASP-dependent actin bundling required for muscle stem cell fusion (PMID:41980967). RNASET2 protein abundance is controlled by FBXO6, which directly binds it and catalyzes K48-linked polyubiquitination and proteasomal degradation (PMID:33767133). In the nervous system, RNASET2 deficiency produces engorged, dysfunctional microglia that fail to clear apoptotic substrate and drive an IFNAR1-dependent type I interferon neuroinflammation, with microglia established as the cellular driver via cell-specific depletion and macrophage rescue (PMID:34764281, PMID:32212285, PMID:38753517).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2005 Medium

    Established that RNASET2's tumor- and metastasis-suppressive activity is separable from its predicted enzymatic role, a finding that reframed the protein as more than an RNase.

    Evidence in vivo ovarian cancer xenograft and metastasis assays with catalytic-site double point mutants

    PMID:15809705

    Open questions at the time
    • Did not identify the molecular mediator of catalysis-independent suppression
    • Mechanism of microenvironmental action not yet defined
  2. 2006 High

    Confirmed RNASET2 is a bona fide acidic endoribonuclease and a glycosylated, secreted, lysosomally localized protein, anchoring its enzymatic and trafficking identity.

    Evidence purified recombinant protein enzymatic assay plus subcellular fractionation/localization

    PMID:16620762

    Open questions at the time
    • In vivo RNA substrates not defined
    • Relationship between secreted and lysosomal pools unresolved
  3. 2006 Medium

    Identified actin binding as a candidate catalysis-independent effector mechanism by showing RNASET2 binds actin and inhibits angiogenesis induced by multiple growth factors.

    Evidence in vitro actin-binding assays, HUVE tube formation, colony formation with enzymatically inactivated protein, xenografts

    PMID:17109444

    Open questions at the time
    • Did not map the actin-binding region
    • Link between actin binding and antiangiogenesis correlative
  4. 2010 Medium

    Showed the oncosuppressive effect operates non-cell-autonomously through recruitment of monocyte/macrophage-lineage immune cells, identifying a microenvironmental mechanism.

    Evidence in vivo ovarian xenografts with immune cell recruitment analysis and negative in vitro cancer-cell assays

    PMID:21189302

    Open questions at the time
    • Macrophage polarization state not yet characterized
    • Signal recruiting immune cells unknown
  5. 2011 High

    Established RNASET2 deficiency as a lysosomal storage disorder by showing loss causes accumulation of undigested rRNA in neuronal lysosomes with white matter pathology.

    Evidence zebrafish genetic mutant with lysosomal imaging, MRI microimaging, and APP/astrocyte IHC

    PMID:21199949

    Open questions at the time
    • Cellular driver of neuropathology not yet pinpointed
    • Inflammatory mechanism not addressed
  6. 2011 Medium

    Extended RNASET2 localization to the secretory pathway and P-bodies, linking it to cytoplasmic RNA granule biology under metabolic stress.

    Evidence fluorescence co-localization with TGN/PM/P-body markers, VSVG trafficking, and knockdown P-body counting

    PMID:22188480

    Open questions at the time
    • Mechanism of P-body involvement undefined
    • Does not connect P-body role to enzymatic or microenvironmental functions
  7. 2014 Medium

    Demonstrated a pro-apoptotic activity via direct TRAF2 interaction, and confirmed actin remodeling by an RNase-dead truncation, separating catalytic from cytoskeletal functions in melanocytes.

    Evidence overexpression apoptosis assays with TRAF2 Co-IP; truncation mutagenesis with in vitro actin-binding and angiogenesis/tumor assays

    PMID:24457966 PMID:25426551

    Open questions at the time
    • TRAF2 interaction shown by single Co-IP without structural detail
    • Physiological context of TRAF2-caspase axis unclear
  8. 2015 Medium

    Defined a catalysis-dependent function in stress-induced cell death and connected RNASET2 levels to actin organization, adhesion, and motility, splitting its activities into distinct mechanistic branches.

    Evidence loss-of-function/haploinsufficiency ROS assays, Drosophila fat-body knockdown; ovarian cancer cell actin/adhesion/motility assays; shootin1 interaction by proteome microarray and Co-IP

    PMID:25797262 PMID:26206090 PMID:26293343

    Open questions at the time
    • Substrate driving ROS-dependent death not identified
    • Mechanistic link between shootin1/actin binding and motility incomplete
  9. 2017 High

    Localized a functional pool of RNASET2 to the mitochondrial intermembrane space and assigned it responsibility for mitochondrial RNA degradation, revealing an unexpected mitochondrial compartment role.

    Evidence mitochondrial sub-compartment fractionation with knockdown/overexpression and RNA decay assays in HEK293

    PMID:28730546

    Open questions at the time
    • Import mechanism into IMS unknown
    • Regulation of compartment-specific targeting undefined
  10. 2018 High

    Expanded mitochondrial RNASET2's role to degradation of outer-membrane-associated cytosolic rRNAs with compensatory feedback on nuclear rRNA transcription and translation, linking it to global RNA economy.

    Evidence fractionation, rRNA decay measurements, knockdown/overexpression in HEK293 and mouse cells, translation assays

    PMID:30385512

    Open questions at the time
    • Mechanism of feedback to nuclear transcription not resolved
    • Selectivity for OMM-associated rRNAs not explained
  11. 2018 Medium

    Connected RNASET2 to macrophage polarization and a sperm-tail AKAP4 signaling axis, broadening its extracellular and tissue-specific functional repertoire.

    Evidence in vitro macrophage M1/M2 polarization with recombinant protein; sperm Co-IP/MS with AKAP4 and PKA/PI3K/calcium readouts plus cAMP rescue

    PMID:29581387 PMID:30218741

    Open questions at the time
    • Receptor mediating macrophage effect not identified here
    • Physiological relevance of sperm AKAP4 interaction unclear
  12. 2019 Medium

    Identified an ECM-dependent, cell-autonomous oncosuppressive branch acting through reduced Src kinase activation, refining the non-enzymatic mechanism.

    Evidence silencing/overexpression in EOC lines with phospho-Src, ECM adhesion, and growth assays

    PMID:30813308

    Open questions at the time
    • Molecular link between RNASET2 and ECM not defined
    • Connection to actin-binding branch not established
  13. 2020 Medium

    Demonstrated in vivo that RNASET2 drives M1 macrophage recruitment, MDSC/M2 suppression, CD8+ T cell expansion, and durable immune memory, and established microglia as the cellular driver of leukoencephalopathy.

    Evidence syngeneic mouse tumor model with immune phenotyping and re-challenge; zebrafish microglia-specific depletion/rescue with live imaging and EM

    PMID:32197460 PMID:32212285

    Open questions at the time
    • Receptor/signal for immune recruitment unresolved
    • Whether tumor and CNS macrophage roles share a mechanism unknown
  14. 2021 High

    Defined post-translational control of RNASET2 abundance via FBXO6-mediated K48 ubiquitination and proteasomal degradation, and established an IFNAR1-dependent type I interferon mechanism for the neuroinflammatory disease.

    Evidence Co-IP, ubiquitination assays, FBA domain mapping, proteasome inhibition; CRISPR knockout mice with ISG profiling, IFNAR1 blocking, and snRNA-seq

    PMID:33767133 PMID:34764281

    Open questions at the time
    • Signal triggering FBXO6 recognition not defined
    • Source of the interferon-stimulating ligand (accumulated RNA) not directly proven
  15. 2023 Medium

    Connected RNASET2 enzymatic RNA degradation to a uridine-glucuronate-cholesterol metabolic axis driving MET-dependent HCC metastasis, and placed the FBXO6/RNASET2 axis under MSI2 control in vascular disease.

    Evidence KO cells/mice with metabolomics, UGT1A1 and cholesterol analysis, MET inhibition rescue; RIP/Co-IP and atherosclerosis mouse model for MSI2-FBXO6

    PMID:37633478 PMID:39903758

    Open questions at the time
    • Quantitative contribution of RNA-derived uridine to cholesterol pool uncertain
    • Tissue specificity of MSI2/FBXO6 regulation not generalized
  16. 2025 High

    Resolved a receptor-to-cytoskeleton signaling pathway: macrophage-secreted RNASET2 enters target cells via the mannose receptor and binds SLK to activate N-WASP-driven actin bundling required for muscle stem cell fusion, and confirmed microglial rescue of CNS pathology.

    Evidence recombinant protein, mannose receptor blocking, RNASET2-SLK Co-IP, N-WASP/Paxillin phospho assays, macrophage-specific KO in mouse and zebrafish; macrophage transplantation into zebrafish with imaging, RNA-seq, behavior

    PMID:38753517 PMID:41980967

    Open questions at the time
    • Whether the SLK/N-WASP pathway underlies the antitumor actin functions not tested
    • Structural basis of RNASET2-SLK interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how RNASET2 partitions between its catalysis-dependent RNA-homeostasis roles and its catalysis-independent secreted signaling functions, and whether a unifying molecular trigger directs the protein to lysosome, mitochondrial IMS, or extracellular signaling fates.
  • No structural model linking actin/SLK binding to catalytic domain
  • Mechanism directing subcellular partitioning unknown
  • Identity of the immunostimulatory RNA species in disease not directly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0008092 cytoskeletal protein binding 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005576 extracellular region 3 GO:0005764 lysosome 3 GO:0005739 mitochondrion 2 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-392499 Metabolism of proteins 1
Partners
AKAP4FBXO6MSI2SHTN1SLKTRAF2

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 RNASET2 is an acidic endoribonuclease with demonstrated catalytic (RNase) activity, as shown using purified recombinant protein expressed in the Baculovirus Expression Vector System and in a human cell line. The protein exists in multiple forms including a full-length glycosylated secreted form and proteolytic products, and localizes to lysosomes. Recombinant protein expression, enzymatic activity assay, subcellular fractionation/localization Archives of biochemistry and biophysics High 16620762
2005 RNASET2 suppresses tumorigenesis and metastasis in ovarian cancer cell lines in vivo; this activity is not dependent on ribonuclease catalytic activity, as a double point mutation at the putative catalytic sites did not abolish tumor/metastasis suppression. In vivo xenograft assay, site-directed mutagenesis of catalytic residues, metastasis assay International journal of oncology Medium 15809705
2006 Recombinant RNASET2 binds actin in vitro and inhibits angiogenesis (tube formation) induced by angiogenin, bFGF, and VEGF in HUVE cells; its antitumorigenic activity in colony formation assays is independent of enzymatic activity (catalytically inactive EI-RNASET2 retains this activity). Actin-binding assay (membrane blotting, crosslinking), HUVE cell tube formation assay, colony formation assay with enzymatically inactivated protein, xenograft model Cancer Medium 17109444
2010 RNASET2 controls ovarian tumorigenesis in vivo through modification of the cellular microenvironment by inducing recruitment of immunocompetent cells of the monocyte/macrophage lineage; no direct effect on cancer cells was detected in several in vitro assays. In vivo xenograft tumor assay, in vitro functional assays (negative), immune cell recruitment analysis Proceedings of the National Academy of Sciences of the United States of America Medium 21189302
2011 RNASET2 localizes to lysosomes in neurons; loss of rnaset2 in zebrafish leads to accumulation of undigested rRNA within lysosomes in brain neurons, white matter lesions, and accumulation of Amyloid precursor protein at sites of neurodegeneration, establishing familial cystic leukoencephalopathy as a lysosomal storage disorder with rRNA as the storage substrate. Zebrafish genetic mutant model, lysosomal localization by imaging, MRI microimaging, immunohistochemistry for APP and astrocyte markers Proceedings of the National Academy of Sciences of the United States of America High 21199949
2011 RNASET2 traffics through the trans-Golgi network and undergoes delivery to the plasma membrane for secretion. A second intracellular pool co-localizes with P-bodies, and this co-localization increases upon metabolic stress. Cells lacking RNASET2 show reduced numbers of P-bodies, indicating RNASET2 is involved in P-body formation. Fluorescence microscopy co-localization with TGN, plasma membrane, and P-body markers; temperature-sensitive VSVG trafficking assay; RNASET2 knockdown with P-body counting Biology of the cell Medium 22188480
2014 Overexpression of RNASET2 in melanocytes induces apoptosis via the TRAF2-caspases pathway; RNASET2 physically interacts with TRAF2, and overexpression inhibits TRAF2 expression. Overexpression in primary melanocytes, apoptosis assays (caspase pathway), co-immunoprecipitation of RNASET2-TRAF2 interaction Cell death & disease Medium 24457966
2015 RNASET2 is required for lipotoxic and oxidative stress-mediated cell death; haploinsufficiency confers increased antioxidant capacity and resistance to ROS-induced death. This function is critically dependent on catalytic activity (unlike its antitumorigenic role). Knockdown of RNASET2 in Drosophila fat body increases survival under oxidative stress. Loss-of-function genetic screen, haploinsufficiency experiments, ROS assays, knockdown in Drosophila (model organism ortholog) Cell death and differentiation Medium 26206090
2017 Mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space (IMS), not the matrix, and is carried out by IMS-localized RNASET2. Biochemical fractionation of mitochondrial compartments, knockdown and overexpression in HEK293 cells, RNA decay assays Protein & cell High 28730546
2018 Mitochondrial IMS RNASET2 also selectively degrades cytosolic rRNAs associated with the mitochondrial outer membrane; this degradation activity positively affects nuclear transcription of rRNAs (compensatory feedback) and influences protein translation inside and outside mitochondria. Biochemical fractionation, rRNA decay measurements, genetic knockdown and overexpression in HEK293 and mouse cells, protein translation assays The Journal of biological chemistry High 30385512
2018 RNASET2 impairs sperm motility by interacting with AKAP4 in the sperm tail, reducing PKA activity, PI3K activity, and intracellular calcium levels; cAMP supplementation rescues motility. Co-immunoprecipitation, mass spectrometry, co-localization by confocal microscopy, RNASET2 protein incubation assay, PKA/PI3K/calcium measurement Reproduction (Cambridge, England) Medium 29581387
2021 FBXO6, a substrate recognition subunit of an SCF E3 ubiquitin ligase complex, directly interacts with RNASET2 and promotes its K48-linked polyubiquitination via its FBA domain, leading to proteasomal degradation of RNASET2. Co-immunoprecipitation, ubiquitination assays, domain mapping (FBA domain), proteasome inhibitor experiments, clinical sample correlation Cell death & disease High 33767133
2021 Rnaset2-/- mice (CRISPR/Cas9-generated) exhibit upregulation of interferon-stimulated genes and IFNAR1-dependent neuroinflammation, with infiltration of CD8+ effector memory T cells and inflammatory monocytes into grey and white matter; single-nuclei RNA sequencing revealed homeostatic dysfunctions in glial cells and neurons. CRISPR/Cas9 knockout mice, ISG expression profiling, immune cell characterization by flow cytometry/IHC, IFNAR1 blocking, single-nuclei RNA sequencing Nature communications High 34764281
2020 Mutant microglia (in rnaset2-deficient zebrafish) display engorged morphology filled with undigested apoptotic cells and undigested substrate; microglia-specific depletion and rescue experiments identified microglia as the cellular driver of the embryonic neuroinflammatory phenotype in RNASET2-deficient leukoencephalopathy. Zebrafish mutant model, live confocal imaging, electron microscopy, microglia-specific depletion and macrophage rescue experiments Glia High 32212285
2015 RNASET2 expression increases following stress induction; changes in RNASET2 levels affect actin cytoskeleton organization, cell adhesion, and motility in ovarian cancer cells in vitro, suggesting cell-autonomous oncosuppressive mechanisms distinct from its microenvironmental role. Stress induction assays, overexpression/knockdown in ovarian cancer cells, actin cytoskeleton imaging, cell adhesion and motility assays Oncotarget Medium 25797262
2015 RNASET2 interacts with shootin1 (an axon outgrowth protein) in vitro as identified by human proteome microarray and confirmed by co-immunoprecipitation; recombinant RNASET2 alters actin network organization in melanocytes and inhibits A375 cell migration. Human proteome microarray, co-immunoprecipitation, actin network imaging, cell migration assay Journal of dermatological science Medium 26293343
2014 A truncated RNASET2 lacking RNase activity (trT2-50, starting at E50) retains actin-binding activity and inhibits angiogenesis and tumorigenesis; trT2-50 binds cell-surface actin and forms a complex with actin in vitro, co-localizes with angiogenin, and disrupts the intracellular actin network of HUVECs. Truncation mutagenesis, in vitro actin-binding assay, HUVE cell tube formation assay, immunofluorescence, xenograft tumor assay Oncotarget Medium 25426551
2018 RNASET2 protein affects macrophage polarization in vitro, promoting a shift toward M1-like (anti-tumor) phenotype and away from M2-like phenotype, as demonstrated by in vitro macrophage polarization assays. In vitro macrophage polarization assay with recombinant RNASET2, transcriptional profiling of M1/M2 markers Immunology letters Medium 30218741
2020 Murine Rnaset2 overexpression in syngeneic tumor models leads to recruitment of CD86+ M1 macrophages, inhibition of MDSCs and M2 macrophages, subsequent expansion of intratumoral CD8+ T cells, and long-term tumor rejection with T cell memory response upon re-challenge. Syngeneic mouse tumor model, immune cell phenotyping by flow cytometry, re-challenge assay Cancers Medium 32197460
2023 RNASET2 deficiency leads to accumulation of cholesterol by hindering RNA degradation into uridine, reducing UTP levels, restraining glucuronate metabolism and UDP-glucuronosyltransferase (UGT1A1) expression, causing decreased bile acid glucuronidation and cholesterol accumulation. Accumulated cholesterol promotes MET receptor-mediated HCC metastasis, which can be reversed by MET knockdown or savolitinib. RNASET2 knockout cells and mouse models, metabolomics (uridine/UTP/glucuronate measurement), UGT1A1 expression analysis, cholesterol measurement, MET activation assay, shRNA/pharmacological MET inhibition rescue Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39903758
2023 MSI2 (Musashi-2) binds FBXO6 to induce Rnaset2 ubiquitination; MSI2 knockdown inhibits VSMC proliferation and migration and suppresses chemokine signaling via the FBXO6/Rnaset2 axis in atherosclerosis. RNA-binding protein immunoprecipitation, co-immunoprecipitation, siRNA knockdown, proliferation/migration assays, in vivo atherosclerosis mouse model Cellular signalling Medium 37633478
2019 RNASET2 expression in epithelial ovarian cancer cells negatively affects growth capability by altering cell interaction with the extracellular matrix, resulting in decreased Src kinase activation, as shown by RNASET2 silencing and overexpression experiments. RNASET2 silencing and overexpression in EOC cell lines, Src activation assay (phospho-Src), ECM adhesion and growth assays Cancers Medium 30813308
2021 Hypoxia enhances RNASET2 expression and secretion in human monocyte-derived dendritic cells via the PI3K/AKT pathway; this expression is almost completely abolished by TLR4 ligand LPS, and parallels HIF-1α accumulation. Hypoxia treatment of primary DCs, RNASET2 ELISA, PI3K/AKT inhibitor experiments, HIF-1α measurement International journal of molecular sciences Medium 34299186
2025 Macrophage-secreted RNASET2 enters muscle stem cells (MuSCs) via the mannose receptor, binds to SLK (Ste20-like kinase), which triggers phosphorylation-mediated activation of N-WASP through Paxillin phosphorylation, enabling actin bundling required for MuSC fusion; macrophages deficient in RNAseT2 show fusion defects and smaller myofibers in vivo. Recombinant protein treatment, mannose receptor blocking, co-immunoprecipitation of RNASET2-SLK interaction, N-WASP/Paxillin phosphorylation assays, macrophage-specific knockout in mouse and zebrafish, in vivo overexpression Nature communications High 41980967
2024 RNASET2 is identified as a lysosomal RNase; cells lacking RNASET2 (together with PLD3 and RNase A family members) accumulate large amounts of lysosomal RNA, establishing RNASET2 as one of the enzymatic effectors of lysosomal RNA degradation. Lysosomal fractionation and RNA profiling, genetic knockout of RNASET2 and other lysosomal RNases, RNA accumulation assays bioRxivpreprint Medium
2024 Transplanted macrophages engraft in rnaset2-deficient zebrafish brains, adopt a microglial phenotype, clear apoptotic cells, rescue antiviral immune overactivation (confirmed by RNA sequencing), and restore normal motor behavior, establishing microglia as the cellular driver of neuropathology in RNASET2 deficiency. Macrophage transplantation into zebrafish embryos, live imaging, tissue clearing, RNA sequencing, behavioral assays Proceedings of the National Academy of Sciences of the United States of America High 38753517
2018 RNASET2 is localized in primary and tertiary granules of neutrophils and is released in association with neutrophil extracellular traps (NETs) upon PMA, Nigericin, or soluble immune complex stimulation. Immunofluorescence co-localization with granule markers, NET induction assays, co-localization of RNASET2 with NET markers Scientific reports Medium 39500942
2022 Recombinant RNASET2 reduces IFN-γ secretion in T cells when added exogenously or overexpressed; disease-risk variant rs2149092 affects allele-specific RNASET2 expression through transcriptional and post-transcriptional mechanisms. T cell activation assays, RNASET2 overexpression and recombinant protein treatment, cytokine ELISA, allele-specific expression assays Frontiers in immunology Medium 36466822
2025 RNASET2 knockdown in a 3D inflammatory thyrocyte spheroid model heightens susceptibility to inflammatory cell death and cytokine expression; recombinant RNASET2 rescue mitigates inflammation and apoptosis, confirming a functional protective role. siRNA knockdown, recombinant RNASET2 rescue, 3D spheroid inflammatory model, apoptosis and cytokine assays Frontiers in endocrinology Medium 41704487

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection. Nature genetics 123 19525954
2011 rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a role for RNase T2 in degrading ribosomal RNA. Proceedings of the National Academy of Sciences of the United States of America 95 21199949
2006 Characterization of RNASET2, the first human member of the Rh/T2/S family of glycoproteins. Archives of biochemistry and biophysics 58 16620762
2006 A recombinant human RNASET2 glycoprotein with antitumorigenic and antiangiogenic characteristics: expression, purification, and characterization. Cancer 56 17109444
2010 Microenvironmental control of malignancy exerted by RNASET2, a widely conserved extracellular RNase. Proceedings of the National Academy of Sciences of the United States of America 55 21189302
2005 Tumor and metastasis suppression by the human RNASET2 gene. International journal of oncology 53 15809705
2014 Stress-induced RNASET2 overexpression mediates melanocyte apoptosis via the TRAF2 pathway in vitro. Cell death & disease 42 24457966
2018 AIF-1 and RNASET2 Play Complementary Roles in the Innate Immune Response of Medicinal Leech. Journal of innate immunity 39 30368505
2020 The failure of microglia to digest developmental apoptotic cells contributes to the pathology of RNASET2-deficient leukoencephalopathy. Glia 38 32212285
2015 RNASET2 is required for ROS propagation during oxidative stress-mediated cell death. Cell death and differentiation 36 26206090
2021 FBXO6-mediated RNASET2 ubiquitination and degradation governs the development of ovarian cancer. Cell death & disease 33 33767133
2017 Mammalian mitochondrial RNAs are degraded in the mitochondrial intermembrane space by RNASET2. Protein & cell 33 28730546
2021 Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy. Nature communications 32 34764281
2008 RNASET2 as a tumor antagonizing gene in a melanoma cancer model. Oncology research 31 18543608
2017 Human recombinant RNASET2-induced inflammatory response and connective tissue remodeling in the medicinal leech. Cell and tissue research 28 28070637
2019 Innate Immune Response Regulation by the Human RNASET2 Tumor Suppressor Gene. Frontiers in immunology 27 31749812
2018 RNASET2 impairs the sperm motility via PKA/PI3K/calcium signal pathways. Reproduction (Cambridge, England) 27 29581387
2018 The human RNASET2 protein affects the polarization pattern of human macrophages in vitro. Immunology letters 26 30218741
2015 Pleiotropic modes of action in tumor cells of RNASET2, an evolutionary highly conserved extracellular RNase. Oncotarget 26 25797262
2013 Molecular characterization and immune modulation properties of Clonorchis sinensis-derived RNASET2. Parasites & vectors 23 24365605
2011 Intracellular trafficking of RNASET2, a novel component of P-bodies. Biology of the cell 23 22188480
2018 Regulation of mitochondrion-associated cytosolic ribosomes by mammalian mitochondrial ribonuclease T2 (RNASET2). The Journal of biological chemistry 22 30385512
2020 Overexpression of Murine Rnaset2 in a Colon Syngeneic Mouse Carcinoma Model Leads to Rebalance of Intra-Tumor M1/M2 Macrophage Ratio, Activation of T Cells, Delayed Tumor Growth, and Rejection. Cancers 21 32197460
2021 Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway. International journal of molecular sciences 19 34299186
2018 RNaseT2 knockout rats exhibit hippocampal neuropathology and deficits in memory. Disease models & mechanisms 19 29752287
2020 Antimicrobial Role of RNASET2 Protein During Innate Immune Response in the Medicinal Leech Hirudo verbana. Frontiers in immunology 18 32210967
2019 RNASET2-deficient leukoencephalopathy mimicking congenital CMV infection and Aicardi-Goutieres syndrome: a case report with a novel pathogenic variant. Orphanet journal of rare diseases 15 31349848
2011 Molecular signature induced by RNASET2, a tumor antagonizing gene, in ovarian cancer cells. Oncotarget 14 21646684
2016 Human recombinant RNASET2: A potential anti-cancer drug. Oncoscience 12 27014725
2012 RNASET2 in human spermatozoa and seminal plasma: a novel relevant indicator for asthenozoospermia. Andrology 12 23258633
2009 Chromosome 6 encoded RNaseT2 protein is a cell growth regulator. Journal of cellular and molecular medicine 12 19382914
2015 RNASET2 tag SNP but not CCR6 polymorphisms is associated with autoimmune thyroid diseases in the Chinese Han population. BMC medical genetics 11 25928629
2023 HIF2α-induced upregulation of RNASET2 promotes triglyceride synthesis and enhances cell migration in clear cell renal cell carcinoma. FEBS open bio 10 36728187
2019 A Cell-Autonomous Oncosuppressive Role of Human RNASET2 Affecting ECM-Mediated Oncogenic Signaling. Cancers 10 30813308
2017 RNASET2, GPR174, and PTPN22 gene polymorphisms are related to the risk of liver damage associated with the hyperthyroidism in patients with Graves' disease. Journal of clinical laboratory analysis 10 28568286
2011 Comparison of the baculovirus-insect cell and Pichia pastoris heterologous systems for the expression of the human tumor suppressor protein RNASET2. Biotechnology and applied biochemistry 10 21446958
2014 Human recombinant truncated RNASET2, devoid of RNase activity; A potential cancer therapeutic agent. Oncotarget 9 25426551
2022 Human RNASET2: A Highly Pleiotropic and Evolutionary Conserved Tumor Suppressor Gene Involved in the Control of Ovarian Cancer Pathogenesis. International journal of molecular sciences 8 36012339
2018 New insights into hypoxia-related mechanisms involved in different microvascular patterns of bronchopulmonary carcinoids and poorly differentiated neuroendocrine carcinomas. Role of ribonuclease T2 (RNASET2) and HIF-1α. Human pathology 8 29763721
2015 Rnaset2 inhibits melanocyte outgrowth possibly through interacting with shootin1. Journal of dermatological science 8 26293343
2014 Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization. Oncoscience 8 25815360
2020 Zebrafish disease model of human RNASET2-deficient cystic leukoencephalopathy displays abnormalities in early microglia. Biology open 7 32295832
2012 RNASET2--an autoantigen in anaplastic large cell lymphoma identified by protein array analysis. Journal of proteomics 7 22732457
2024 PTGES2 and RNASET2 identified as novel potential biomarkers and therapeutic targets for basal cell carcinoma: insights from proteome-wide mendelian randomization, colocalization, and MR-PheWAS analyses. Frontiers in pharmacology 6 39035989
2022 Myelin oligodendrocyte glycoprotein-associated disease is associated with BANK1, RNASET2 and TNIP1 polymorphisms. Journal of neuroimmunology 6 36054934
2022 A potential role of human RNASET2 overexpression in the pathogenesis of Graves' disease. Endocrine 6 36180758
2025 RNASET2 Deficiency Induces Hepatocellular Carcinoma Metastasis through Cholesterol-Triggered MET Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 39903758
2024 Macrophage transplantation rescues RNASET2-deficient leukodystrophy by replacing deficient microglia in a zebrafish model. Proceedings of the National Academy of Sciences of the United States of America 5 38753517
2022 Diagnostic and therapeutic potential of RNASET2 in Crohn's disease: Disease-risk polymorphism modulates allelic-imbalance in expression and circulating protein levels and recombinant-RNASET2 attenuates pro-inflammatory cytokine secretion. Frontiers in immunology 5 36466822
2024 Regulation of neutrophil associated RNASET2 expression in rheumatoid arthritis. Scientific reports 4 39500942
2024 Exploring the role of RNASET2 in the immune response of black soldier fly larvae. Archives of insect biochemistry and physiology 3 39190478
2023 Musashi-2 binds with Fbxo6 to induce Rnaset2 ubiquitination and chemokine signaling pathway during vascular smooth muscle cell phenotypic switch in atherosclerosis. Cellular signalling 3 37633478
2015 New Strategies for Expression and Purification of Recombinant Human RNASET2 Protein in Pichia pastoris. Molecular biotechnology 3 25663099
2025 A Multi-omic study integrating plasma protein, multiple tissues, and single-cell identifies RNASET2 as a key gene for lung cancer. Discover oncology 2 39930075
2024 Pathogenic Roles for RNASET2 in Clear Cell Renal Cell Carcinoma. Laboratory investigation; a journal of technical methods and pathology 2 38431116
2020 Expression and purification of the human tumor suppressor protein RNASET2 in CHO-S cells. Protein expression and purification 1 32450138
2013 [Association of RNASET2 gene polymorphisms and haplotypes with Graves disease in Han Chinese population from coastal regions of Shandong]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 24327149
2026 Integrative multi-omics Mendelian randomization and functional validation identifies RNASET2 as a novel therapeutic target for autoimmune thyroiditis. Frontiers in endocrinology 0 41704487
2026 Restorative macrophage-derived RNAseT2 stimulates muscle stem cell fusion via an SLK/N-WASP/actin bundling dependent axis. Nature communications 0 41980967
2025 The human RNASET2 alarmin-like molecule differentially affects prostate cancer cells behavior in both cell autonomous and non-cell autonomous manners. Journal of translational medicine 0 40389981
2025 Unlocking microglia pyroptosis in a model of type I interferon-driven neuroinflammation: lessons from Rnaset2-/- mice. Cell death & disease 0 41453865
2018 Novel RNASET2 Pathogenic Variants in an East Asian Child with Delayed Psychomotor Development. Fetal and pediatric pathology 0 29336640

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