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Showing PNPT1 — PNPASE is a alias.

PNPT1

Polyribonucleotide nucleotidyltransferase 1, mitochondrial · UniProt Q8TCS8

Length
783 aa
Mass
86.0 kDa
Annotated
2026-06-10
97 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

PNPT1 (PNPase) is a trimeric 3'-to-5' exoribonuclease of the mitochondrial intermembrane space that governs both the import of nuclear-encoded RNAs into mitochondria and the turnover of mitochondrial transcripts (PMID:20691904, PMID:23084291). Through its KH and S1 RNA-binding domains it recognizes structured nuclear-encoded RNAs — RNase P RNA, 5S rRNA, MRP RNA, miRNA-378, and lncRNAs including Malat1 — and mediates their import into the matrix (PMID:20691904, PMID:38826135, PMID:28709769). In its degradative role PNPT1 partners with the SUV3 helicase (SUPV3L1) to form a mitochondrial degradosome that assembles in discrete RNA- and nucleoid-associated foci and drives processing, polyadenylation, and decay of mitochondrial mRNAs (PMID:23221631, PMID:18083837); this activity is restrained by the LRPPRC/SLIRP complex, which protects specific mtRNAs from degradation (PMID:22661577). Cryo-EM structures resolve loading, pre-catalytic, and catalytic states in which the S1 domains cap the degradation chamber and switch between open and closed conformations to position substrate for Mg2+-dependent phosphorolytic cleavage (PMID:39997218, PMID:41361968). Functional integrity depends on trimer assembly: pathogenic missense mutations that block trimerization, S1-domain closure, or the active site impair RNA import, mtRNA maturation, and mitochondrial translation, causing respiratory-chain deficiency, hereditary hearing loss (DFNB70), and Leigh syndrome (PMID:23084291, PMID:23084290, PMID:30020492, PMID:39997218, PMID:28645153), while heterozygous loss-of-function variants cause spinocerebellar ataxia type 25 (SCA25) (PMID:35411967). By degrading mitochondrial double-stranded RNA, PNPT1 prevents its cytoplasmic accumulation, and loss of this function triggers a type I interferon response through the mt-dsRNA–PKR–eIF2α axis (PMID:35411967, PMID:38412930). During apoptosis, following mitochondrial outer membrane permeabilization, PNPT1 is released into the cytoplasm where it initiates 3'-to-5' decay of mRNAs and poly(A) noncoding RNAs that lack protective 3' stem-loop structures (PMID:29779946).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 Medium

    Established PNPT1 as a 3'-to-5' RNA-degrading enzyme with growth-inhibitory activity, the first functional characterization of the human protein.

    Evidence in vitro RNA degradation assay and colony formation assay with ectopic expression in melanoma cells

    PMID:12473748

    Open questions at the time
    • Cytoplasmic localization claim later refined to mitochondrial IMS
    • No structural or domain-level mechanism defined
    • Physiological substrates unidentified
  2. 2003 Medium

    Defined how PNPT1 is transcriptionally induced, linking it to interferon signaling.

    Evidence promoter/ISRE deletion, EMSA, and IFN-signaling-defective cell lines mapping JAK/STAT-ISGF3 control

    PMID:14563561

    Open questions at the time
    • Does not address downstream consequences of induction
    • Functional role of IFN-driven PNPT1 not tested here
  3. 2007 Medium

    Connected PNPT1 to mitochondrial RNA metabolism, showing it controls mtRNA processing and polyadenylation from the IMS.

    Evidence stable shRNA silencing in HeLa with Northern blot and poly(A) tail analysis of mitochondrial transcripts

    PMID:18083837

    Open questions at the time
    • Effect described as indirect; direct enzymatic mechanism unresolved
    • Partner enzymes not yet identified
  4. 2007 Medium

    Identified a cytotoxic effector pathway downstream of PNPT1, defining how its overexpression drives apoptosis.

    Evidence ectopic overexpression with dominant-negative PKR, antisense, and rescue epistasis for the PKR-eIF2α-GADD153-Bcl-xL axis

    PMID:17804700

    Open questions at the time
    • Mechanistic trigger linking PNPase to PKR activation not defined
    • Performed in melanoma overexpression context only
  5. 2010 High

    Revealed PNPT1's import function, showing it is required to bring nuclear-encoded RNAs into the mitochondrial matrix and that import is separable from processing.

    Evidence RNAi knockdown, subcellular fractionation, RNA interaction assays, and isolation of a mitochondrial RNA targeting signal

    PMID:20691904

    Open questions at the time
    • Domains responsible for RNA recognition not yet mapped
    • Mechanism of translocation across membranes unresolved
  6. 2012 High

    Identified the PNPase-SUV3 degradosome and its spatial organization, establishing the protein machinery for mitochondrial RNA degradation.

    Evidence FLIM-FRET, BiFC, and siRNA silencing demonstrating co-localization in D-foci and functional interdependence

    PMID:23221631

    Open questions at the time
    • Stoichiometry of the complex not defined
    • Regulation of foci assembly unknown
  7. 2012 High

    Linked PNPT1 mutations to human mitochondrial disease and proved trimerization is required for function.

    Evidence BN-PAGE, RNA import and translation assays, and cDNA rescue in patient fibroblasts (c.1160A>G); positional cloning and cross-species complementation for DFNB70 (p.Glu475Gly)

    PMID:23084290 PMID:23084291

    Open questions at the time
    • Structural basis of trimer disruption not yet resolved
    • Tissue-specificity of phenotypes unexplained
  8. 2012 Medium

    Showed PNPase degradation is actively regulated, identifying LRPPRC/SLIRP as a suppressor of mtRNA decay.

    Evidence in vitro reconstitution with purified PNPase, SUV3, and LRPPRC/SLIRP

    PMID:22661577

    Open questions at the time
    • In vivo relevance of suppression not established
    • Mechanism of protection (sequestration vs. blocking) unclear
  9. 2017 Medium

    Distinguished active-site from trimerization defects, showing catalytic activity is needed for correct ND6 transcript maturation.

    Evidence exome sequencing with WT complementation and RNA analysis in patient myoblasts (Leigh syndrome)

    PMID:28645153

    Open questions at the time
    • Single lab
    • Why ND6 transcripts are particularly affected unresolved
  10. 2018 High

    Provided structural insight into disease mutations, showing they trap PNPase as a dimer with inaccessible RNA-binding domains.

    Evidence 2.8 Å crystal structure of dimeric PNPase, SAXS, and RNA-binding assays of Q387R and E475G mutants

    PMID:30020492

    Open questions at the time
    • Functional trimer structure not captured here
    • S1-domain dynamics during catalysis not resolved
  11. 2018 High

    Uncovered a non-mitochondrial role for PNPT1, showing it executes cytoplasmic RNA decay after apoptotic membrane permeabilization.

    Evidence knockdown/ectopic expression, RNase-deficient mutant, MOMP assay, and 3'-stem-loop substrate mutagenesis

    PMID:29779946

    Open questions at the time
    • Physiological consequence of post-MOMP decay for cell death unclear
    • Substrate selection in vivo not fully mapped
  12. 2022 Medium

    Extended the PNPT1 disease spectrum to dominant SCA25 and tied neurological disease to a type I interferon mechanism.

    Evidence WGS/WES linkage with interferon signature measurement in multiple families

    PMID:35411967

    Open questions at the time
    • Causal chain from haploinsufficiency to neuronal loss not demonstrated
    • Tissue selectivity of ataxia phenotype unexplained
  13. 2024 Medium

    Defined the molecular basis of RNA import, mapping KH and S1 domains as the determinants of nuclear-encoded lncRNA recognition.

    Evidence CLIP-seq, KH/S1 domain knockout mutants, in vitro binding, and machine-learning prediction in HL-1 cells

    PMID:38826135

    Open questions at the time
    • Translocation step beyond binding not addressed
    • In vivo import of identified lncRNAs not quantified
  14. 2024 Medium

    Clarified the antiviral/interferon role, showing PNPase restrains cytoplasmic mt-dsRNA to suppress the PKR-eIF2α stress response.

    Evidence siRNA knockdown during viral infection, mt-dsRNA localization, PKR/eIF2α phosphorylation, and drug screen

    PMID:38412930

    Open questions at the time
    • Mechanism by which viruses upregulate PNPT1 not detailed
    • Single lab
  15. 2025 High

    Resolved the complete catalytic cycle, capturing how S1 domains gate the chamber and how substrate is positioned and cleaved.

    Evidence cryo-EM of loading, pre-catalytic, and catalytic states with SAXS, mutagenesis, and Suv3 interaction assays (P467S, G499R, D713Y)

    PMID:39997218 PMID:41361968

    Open questions at the time
    • Structures of full degradosome with SUV3 not resolved
    • Conformational coupling to import function unaddressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PNPT1 mechanically translocates structured RNAs across mitochondrial membranes, and how its degradative versus import functions are coordinated, remain unresolved.
  • No structural model of RNA translocation across the membrane
  • Switch between import and degradation modes uncharacterized
  • Regulation of cytoplasmic vs. mitochondrial activity pools unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 6 GO:0003723 RNA binding 3 GO:0016787 hydrolase activity 2
Localization
GO:0005739 mitochondrion 4 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2
Partners
AGO2GRSF1LRPPRCSLIRPSUPV3L1TCL1
Complex memberships
SUV3-PNPase mitochondrial degradosome

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 PNPASE (PNPT1) localizes in the mitochondrial intermembrane space and is required for import of nuclear-encoded RNAs (RNase P RNA, 5S rRNA, MRP RNA) into the mitochondrial matrix; RNA processing and import activities are separable functions, and a mitochondrial RNA targeting signal was isolated that enables RNA import in a PNPASE-dependent manner. RNAi knockdown, RNA hybridization, subcellular fractionation, PNPASE-imported RNA interaction assays, mitochondrial targeting signal characterization Cell High 20691904
2012 Human PNPase (PNPT1) and hSuv3 helicase (SUPV3L1) form a mitochondrial RNA-degrading complex (degradosome) exclusively in distinct mitochondrial foci (D-foci) that co-localize with mitochondrial RNA and nucleoids; interaction between PNPase and hSuv3 is essential for efficient mitochondrial RNA degradation. FLIM-FRET, bimolecular fluorescence complementation (BiFC), siRNA silencing with RNA decay intermediate accumulation assay Nucleic acids research High 23221631
2012 A PNPT1 missense mutation (c.1160A>G) disrupts PNPase trimerization (no PNPase complex detected by BN-PAGE), impairs 5S rRNA and MRP RNA import into mitochondria, reduces mitochondrial translation rate, and causes respiratory-chain deficiency; wild-type PNPT1 overexpression rescues 5S rRNA import and mitochondrial translation. Blue-native PAGE, RNA hybridization, mitochondrial translation rate measurement, cDNA rescue experiment in patient fibroblasts American journal of human genetics High 23084291
2012 A PNPT1 missense mutation (c.1424A>G; p.Glu475Gly) within the second RNase-PH domain results in hypofunctional protein with disturbed PNPase trimerization and impaired mitochondrial RNA import, causing hereditary hearing loss (DFNB70). Positional cloning, in vitro complementation in bacteria/yeast/mammalian cells, trimerization assay, RNA import assay American journal of human genetics High 23084290
2018 During apoptosis, PNPT1 is released from the mitochondrial intermembrane space following mitochondrial outer membrane permeabilization (MOMP) and directly initiates 3'-to-5' decay of mRNAs and poly(A) noncoding RNAs; decay requires RNase activity (RNase-deficient mutant inactive); substrates require single-stranded 3' ends — adding a 3'-stem-loop to an mRNA prevents its decay, and disrupting the 3'-stem-loop of a decay-resistant ncRNA renders it susceptible. PNPT1 knockdown/ectopic expression, RNase-deficient mutant, 3'-stem-loop mutagenesis, MOMP assay, RNA decay measurement Cell High 29779946
2018 Disease-linked human PNPase mutants Q387R and E475G form dimers instead of the functional trimer, have significantly lower RNA binding and degradation activities; the S1 domain is required for binding structured (stem-loop) RNA but not single-stranded RNA; in the dimeric assembly, KH and S1 RNA-binding domains are relatively inaccessible. Crystal structure of dimeric PNPase (2.8 Å), SAXS, RNA binding assays, mutagenesis Nucleic acids research High 30020492
2002 Human PNPase (hPNPase old-35/PNPT1) localizes in the cytoplasm of human cells and induces RNA degradation in vitro; ectopic expression reduces colony formation in melanoma cells, confirming growth-inhibitory activity. Subcellular localization (immunofluorescence), in vitro RNA degradation assay, colony formation assay with ectopic expression Proceedings of the National Academy of Sciences of the United States of America Medium 12473748
2007 PNPase RNAi silencing in HeLa cells significantly affects processing and polyadenylation of mitochondrial mRNAs (e.g., abolishes stable poly(A) tails on COX1 transcripts), demonstrating that PNPase located in the mitochondrial IMS is involved in mtRNA processing and polyadenylation by indirect means. Stable shRNA silencing, Northern blot analysis, poly(A) tail length analysis RNA (New York, N.Y.) Medium 18083837
2012 LRPPRC/SLIRP complex suppresses PNPase-mediated 3' exonucleolytic degradation of mitochondrial mRNAs in vitro, linking PNPase to regulated mRNA stability in human mitochondria. In vitro RNA degradation assay with purified components (PNPase, SUV3, LRPPRC/SLIRP) Nucleic acids research Medium 22661577
2017 PNPT1 compound heterozygous variants (active-site mutations) do not affect PNPase trimer formation but cause accumulation of specific RNA processing intermediates from ND6 transcripts and small mRNA fragments, indicating PNPase activity is essential for correct maturation of ND6 mitochondrial transcripts and removal of degradation intermediates. Exome sequencing, wild-type PNPT1 complementation in patient myoblasts, RNA analysis (Northern blot/RT-PCR), structural prediction Human molecular genetics Medium 28645153
2006 TCL1 oncoprotein physically interacts with PNPase through its AKT interaction domain binding to either RNase PH repeat domain of PNPase, without influencing PNPase RNA degrading activity. Co-immunoprecipitation, protein docking modeling, in vitro RNA degradation assay Cancer letters Medium 16934922
2007 Overexpression of hPNPase(old-35) induces apoptosis in melanoma cells via activation of double-stranded RNA-dependent protein kinase (PKR), leading to eIF2α phosphorylation, GADD153 induction, shutdown of protein synthesis, and downregulation of Bcl-xL; a dominant-negative PKR inhibitor blocks this apoptosis pathway. Ectopic overexpression, dominant-negative inhibitor, Western blotting for PKR, eIF2α, GADD153, Bcl-xL; Bcl-xL overexpression and GADD153 antisense rescue Cancer research Medium 17804700
2019 IFN-α induces upregulation of PNPT1 in pancreatic β cells, which causes degradation of miR-26a, leading to upregulation of TET2 enzyme and increased 5-hydroxymethylcytosine (DNA demethylation) at inflammatory/immune gene loci; IFN-α-specific β cell expression in transgenic mice led to T1D development through a PNPT1/TET2-dependent mechanism. Human islet IFN-α treatment, miR-26a and TET2 expression analysis, 5-hmC measurement, IFNα-INS1CreERT2 transgenic mouse model JCI insight Medium 30721151
2023 Pnpt1 deficiency in macrophages enhances NLRP3 inflammasome-dependent IL-1β/IL-18 release; this inflammasome activation is dependent on increased glycolysis and expression of mitochondrial antiviral-signaling protein (MAVS), but not NF-κB signaling; Pnpt1-deficient macrophages show increased glycolysis after LPS and increased mt-ROS after NLRP3 activation. Myeloid-specific Pnpt1 knockout mice, peritoneal/BMDM cultures, LPS/nigericin/ATP/poly(I:C) stimulation, IL-1β/IL-18 ELISA, glycolysis measurement, mt-ROS assay, MAVS dependency assay Cellular & molecular immunology Medium 36596874
2018 PNPase contributes to mitochondrial miRNA import through transport of miRNA-378; Ago2 and PNPase associate, with increased association in diabetic state; PNPase overexpression in HL-1 cardiomyocytes increases mitochondrial miRNA-378 levels leading to decreased ATP6 levels and ATP synthase activity. Co-immunoprecipitation (Ago2-PNPase), PNPase overexpression in HL-1 cells, mitochondrial miRNA quantification, ATP synthase activity assay Journal of molecular and cellular cardiology Medium 28709769
2025 Cryo-EM structures of human PNPase in three functional states (loading, pre-catalytic, catalytic) reveal that S1 domains cap the RNA-degradation chamber and shift between open and closed conformations; disease-associated mutations P467S and G499R impair S1 domain closure and reduce stem-loop RNA binding and degradation; D713Y mutation in the S1 domain does not affect RNA-binding affinity but diminishes interaction with Suv3 helicase for cooperative degradation of structured RNA. Cryo-EM structure determination, SAXS, mutagenesis, RNA binding and degradation assays, Suv3 interaction assay Nucleic acids research High 39997218
2025 Cryo-EM structures of hPNPase during RNA degradation show that flexible loops facilitate substrate RNA recruitment and guide it to the active site; terminal nucleotides reorient (base flipping) in the pre-catalytic state positioning the RNA backbone for cleavage stabilized by Mg2+; the catalytic state shows nucleophilic attack of phosphate on the RNA backbone mediated by key active-site residues. High-resolution cryo-EM of three functional states (loading, pre-catalytic, catalytic) Nucleic acids research High 41361968
2018 PNPase mitochondrial IMS localization during mitochondrial RNA processing; PNPT1 variants causing disease result in defective RNA processing and/or trimerization; functional PNPT1 transcripts accumulate unprocessed intermediates in patient fibroblasts; blood shows increased interferon response. cDNA splicing analysis, patient fibroblast RNA processing analysis, interferon score measurement Journal of clinical medicine Medium 31752325
2022 Heterozygous loss-of-function PNPT1 variants (nonsense and splice variants in the S1 domain) cause spinocerebellar ataxia type 25 (SCA25); affected carriers show elevated type I interferon response, consistent with PNPase preventing abnormal accumulation of double-stranded mtRNAs and their cytoplasmic leakage. WGS/WES with linkage analysis, interferon signature measurement in patient blood, structural/functional variant analysis Annals of neurology Medium 35411967
2024 PNPT1 knockdown prevents cytoplasmic accumulation of mitochondrial double-stranded RNAs; viruses upregulate PNPT1 to suppress integrated stress response; inhibition of PNPT1 causes mt-dsRNA relocation to cytoplasm, activating PKR → eIF2α phosphorylation → translation suppression and viral propagation blockade. PNPT1 siRNA knockdown during viral infection, mt-dsRNA localization assay, PKR/eIF2α phosphorylation Western blot, lanatoside C drug screen International journal of antimicrobial agents Medium 38412930
2017 PNPT1 mutations causing Leigh syndrome disrupt PNPase active site but do not affect trimer formation, causing accumulation of RNA processing intermediates from ND6 and other mitochondrial transcripts; wild-type PNPT1 expression in patient myoblasts complemented the defects. Exome sequencing, wild-type PNPT1 complementation in patient myoblasts, RNA analysis, BN-PAGE, structural prediction Human molecular genetics Medium 28645153
2018 The mitochondrial degradosome SUV3-PNPase complex, together with co-factor GRSF1 (which melts G-quadraplexes), restricts antisense mitochondrial RNAs that form G-quadraplexes. SUV3/PNPase/GRSF1 interaction and functional analyses in mitochondrial RNA surveillance Molecular & cellular oncology Low 30525095
2003 IFN-β controls hPNPase(old-35)/PNPT1 expression by transcriptional modulation via the interferon stimulatory response element (ISRE) in its promoter; transcriptional activation is mediated by the ISGF3 complex through the JAK/STAT pathway. Promoter analysis, ISRE deletion, gel shift (EMSA) assay, cell lines defective in IFN signaling molecules Gene Medium 14563561
2024 PNPase KH and S1 domains mediate binding of nuclear-encoded lncRNAs (including Malat1) in the mitochondrion; knockout of KH and S1 domains in HL-1 cells decreases lncRNA binding to PNPase; sequence and secondary structural features identified by machine learning predict lncRNA binding to PNPase for mitochondrial import. Cross-linked immunoprecipitation (CLIP) sequencing, KH/S1 domain knockout mutants, in vitro fluorescence binding assays, machine learning (CART, SVM) American journal of physiology. Cell physiology Medium 38826135
2022 In patient fibroblasts with PNPT1 compound heterozygous mutations, there is reduced RNA import of RNase P into mitochondria; exogenous wild-type PNPT1 (but not mutants) rescues ATP production, confirming pathogenicity; skin fibroblasts show markedly decreased PNPase expression. Exome sequencing, RNA import assay (RNase P), ATP production assay, wild-type/mutant PNPT1 rescue expression Clinical genetics Medium 28594066
2022 SP1 and NFY transcription factors bind the PNPT1 promoter and regulate PNPT1 expression and mitochondrial activity, as demonstrated by EMSA, ChIP, luciferase reporter assays, and siRNA-based mRNA silencing. Luciferase reporter assays, EMSA, ChIP, siRNA silencing, RT-qPCR International journal of molecular sciences Medium 36232701
2022 OGD (oxygen-glucose deprivation) increases PNPT1 protein levels in the cytoplasm of HL-1 mouse atrial myocytes; PNPT1 knockdown reduces OGD-induced degradation of ACTB and TUBA mRNAs, reduces apoptosis rate, increases mitochondrial membrane potential, and improves mitochondrial morphology. PNPT1-siRNA knockdown, qPCR for mRNA targets, flow cytometry (apoptosis), JC-1 mitochondrial membrane potential assay, electron microscopy Nan fang yi ke da xue xue bao Low 35527495
1998 Negative result: miR-183-5p directly targets the 3' UTR of PNPT1 mRNA to suppress its expression, reversing the tumor-suppressive role of PNPT1 in bladder cancer cells. Dual-luciferase reporter assay (3' UTR targeting), PNPT1 overexpression/depletion, in vitro apoptosis assay Current medical science Low 35788944
1998 PREPRINT — In glioblastoma, temozolomide treatment triggers a feed-forward loop between PNPT1 and miR-181d: ATR kinase activation causes PNPT1-dependent degradation of miR-181d, increasing MGMT expression variance and temozolomide resistance; this resistance is suppressed by exogenous miR-181d. Feed-forward loop characterization, ATR inhibition, PNPT1 knockdown, miR-181d overexpression, MGMT expression variance analysis bioRxivpreprint Low bio_10.1101_2025.04.22.650094

Source papers

Stage 0 corpus · 97 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Copurification of E. coli RNAase E and PNPase: evidence for a specific association between two enzymes important in RNA processing and degradation. Cell 394 7510217
2010 PNPASE regulates RNA import into mitochondria. Cell 304 20691904
2012 Human mitochondrial RNA decay mediated by PNPase-hSuv3 complex takes place in distinct foci. Nucleic acids research 188 23221631
2001 Acquirement of cold sensitivity by quadruple deletion of the cspA family and its suppression by PNPase S1 domain in Escherichia coli. Molecular microbiology 174 11298285
2012 LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria. Nucleic acids research 162 22661577
2002 Identification and cloning of human polynucleotide phosphorylase, hPNPase old-35, in the context of terminal differentiation and cellular senescence. Proceedings of the National Academy of Sciences of the United States of America 108 12473748
1994 Roles of RNase E, RNase II and PNPase in the degradation of the rpsO transcripts of Escherichia coli: stabilizing function of RNase II and evidence for efficient degradation in an ams pnp rnb mutant. The EMBO journal 101 7519147
2002 DEAD box RhlB RNA helicase physically associates with exoribonuclease PNPase to degrade double-stranded RNA independent of the degradosome-assembling region of RNase E. The Journal of biological chemistry 94 12181321
2003 A Streptomyces coelicolor functional orthologue of Escherichia coli RNase E shows shuffling of catalytic and PNPase-binding domains. Molecular microbiology 92 12675796
2008 Crystal structure of Escherichia coli PNPase: central channel residues are involved in processive RNA degradation. RNA (New York, N.Y.) 91 18812438
2001 PNPase autocontrols its expression by degrading a double-stranded structure in the pnp mRNA leader. The EMBO journal 90 11726520
2012 The crucial role of PNPase in the degradation of small RNAs that are not associated with Hfq. RNA (New York, N.Y.) 89 22355164
2002 PNPase activity determines the efficiency of mRNA 3'-end processing, the degradation of tRNA and the extent of polyadenylation in chloroplasts. The EMBO journal 87 12486011
2012 Mutation in PNPT1, which encodes a polyribonucleotide nucleotidyltransferase, impairs RNA import into mitochondria and causes respiratory-chain deficiency. American journal of human genetics 84 23084291
2002 Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. Journal of molecular biology 82 12419256
2018 PNPT1 Release from Mitochondria during Apoptosis Triggers Decay of Poly(A) RNAs. Cell 76 29779946
2017 Exploring the mitochondrial microRNA import pathway through Polynucleotide Phosphorylase (PNPase). Journal of molecular and cellular cardiology 75 28709769
2012 A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss. American journal of human genetics 75 23084290
2007 Stable PNPase RNAi silencing: its effect on the processing and adenylation of human mitochondrial RNA. RNA (New York, N.Y.) 71 18083837
2014 A PNPase dependent CRISPR System in Listeria. PLoS genetics 68 24415952
2008 PNPase is a key player in the regulation of small RNAs that control the expression of outer membrane proteins. RNA (New York, N.Y.) 67 18203924
2011 PNPASE and RNA trafficking into mitochondria. Biochimica et biophysica acta 65 22023881
2023 Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages. Cellular & molecular immunology 61 36596874
1996 PNPase modulates RNase II expression in Escherichia coli: implications for mRNA decay and cell metabolism. Molecular microbiology 60 8809756
2015 Next generation sequencing analysis reveals that the ribonucleases RNase II, RNase R and PNPase affect bacterial motility and biofilm formation in E. coli. BMC genomics 55 25757888
2005 RhlB helicase rather than enolase is the beta-subunit of the Escherichia coli polynucleotide phosphorylase (PNPase)-exoribonucleolytic complex. Proceedings of the National Academy of Sciences of the United States of America 54 16275923
2007 The PNPase, exosome and RNA helicases as the building components of evolutionarily-conserved RNA degradation machines. Journal of biomedical science 51 17514363
2017 Defective mitochondrial RNA processing due to PNPT1 variants causes Leigh syndrome. Human molecular genetics 47 28645153
1994 Decay of the IS10 antisense RNA by 3' exoribonucleases: evidence that RNase II stabilizes RNA-OUT against PNPase attack. Molecular microbiology 47 7531807
2003 Expression regulation and genomic organization of human polynucleotide phosphorylase, hPNPase(old-35), a Type I interferon inducible early response gene. Gene 46 14563561
2016 Regulation and functions of bacterial PNPase. Wiley interdisciplinary reviews. RNA 41 26750178
2021 A cooperative PNPase-Hfq-RNA carrier complex facilitates bacterial riboregulation. Molecular cell 37 34157309
2016 Whole-exome sequencing identifies novel variants in PNPT1 causing oxidative phosphorylation defects and severe multisystem disease. European journal of human genetics : EJHG 34 27759031
2020 PNPT1 mutations may cause Aicardi-Goutières-Syndrome. Brain & development 31 33158637
2017 Novel biallelic mutations in the PNPT1 gene encoding a mitochondrial-RNA-import protein PNPase cause delayed myelination. Clinical genetics 31 28594066
2019 Epigenetic modulation of β cells by interferon-α via PNPT1/mir-26a/TET2 triggers autoimmune diabetes. JCI insight 30 30721151
2015 CsrA Participates in a PNPase Autoregulatory Mechanism by Selectively Repressing Translation of pnp Transcripts That Have Been Previously Processed by RNase III and PNPase. Journal of bacteriology 29 26438818
2019 Clinical Spectrum and Functional Consequences Associated with Bi-Allelic Pathogenic PNPT1 Variants. Journal of clinical medicine 28 31752325
2021 Circ-PNPT1 contributes to gestational diabetes mellitus (GDM) by regulating the function of trophoblast cells through miR-889-3p/PAK1 axis. Diabetology & metabolic syndrome 25 34074335
2012 Escherichia coli cold-shock gene profiles in response to over-expression/deletion of CsdA, RNase R and PNPase and relevance to low-temperature RNA metabolism. Genes to cells : devoted to molecular & cellular mechanisms 23 22957931
2018 PNPase is involved in the coordination of mRNA degradation and expression in stationary phase cells of Escherichia coli. BMC genomics 22 30486791
2023 RNase E biomolecular condensates stimulate PNPase activity. Scientific reports 21 37558691
2006 The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity. Cancer letters 21 16934922
2022 Heterozygous PNPT1 Variants Cause Spinocerebellar Ataxia Type 25. Annals of neurology 20 35411967
2010 Regulatory mechanisms of exoribonuclease PNPase and regulatory small RNA on T3SS of Dickeya dadantii. Molecular plant-microbe interactions : MPMI 20 20831411
2010 Human polynucleotide phosphorylase (hPNPase(old-35)): an evolutionary conserved gene with an expanding repertoire of RNA degradation functions. Oncogene 20 21151174
2009 Bacillus subtilis trp Leader RNA: RNase J1 endonuclease cleavage specificity and PNPase processing. The Journal of biological chemistry 20 19638340
1990 Histochemical demonstration of purine nucleoside phosphorylase (PNPase) in microglial and astroglial cells of adult rat brain. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20 2120328
2018 Crystal structure of dimeric human PNPase reveals why disease-linked mutants suffer from low RNA import and degradation activities. Nucleic acids research 19 30020492
2018 Controlling the mitochondrial antisense - role of the SUV3-PNPase complex and its co-factor GRSF1 in mitochondrial RNA surveillance. Molecular & cellular oncology 19 30525095
2024 Young (<35 years) haploidentical versus old (≥35 years) mismatched unrelated donors and vice versa for allogeneic stem cell transplantation with post-transplant cyclophosphamide in patients with acute myeloid leukemia in first remission: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone marrow transplantation 18 39155338
2022 PNPase and RhlB Interact and Reduce the Cellular Availability of Oxidized RNA in Deinococcus radiodurans. Microbiology spectrum 18 35856907
2018 Is PNPT1-related hearing loss ever non-syndromic? Whole exome sequencing of adult siblings expands the natural history of PNPT1-related disorders. American journal of medical genetics. Part A 18 30244537
2012 The Yersinia pseudotuberculosis degradosome is required for oxidative stress, while its PNPase subunit plays a degradosome-independent role in cold growth. FEMS microbiology letters 18 23082859
2014 Rapid degradation of Hfq-free RyhB in Yersinia pestis by PNPase independent of putative ribonucleolytic complexes. BioMed research international 17 24818153
2006 Human polynucleotide phosphorylase (hPNPase old-35): an RNA degradation enzyme with pleiotrophic biological effects. Cell cycle (Georgetown, Tex.) 16 16687933
2017 Enolase binds to RnpA in competition with PNPase in Staphylococcus aureus. FEBS letters 15 28960276
2009 Adenovirus-mediated hPNPase(old-35) gene transfer as a therapeutic strategy for neuroblastoma. Journal of cellular physiology 14 19202553
2020 Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both? Journal of medical genetics 13 33199448
2016 The small RNA SraG participates in PNPase homeostasis. RNA (New York, N.Y.) 13 27495318
2015 The Protein Interaction of RNA Helicase B (RhlB) and Polynucleotide Phosphorylase (PNPase) Contributes to the Homeostatic Control of Cysteine in Escherichia coli. The Journal of biological chemistry 12 26494621
2013 A conserved loop in polynucleotide phosphorylase (PNPase) essential for both RNA and ADP/phosphate binding. Biochimie 12 24075876
2008 Progression elevated gene-3 promoter (PEG-Prom) confers cancer cell selectivity to human polynucleotide phosphorylase (hPNPase(old-35))-mediated growth suppression. Journal of cellular physiology 12 17960560
2006 Up-regulation of human PNPase mRNA by beta-interferon has no effect on protein level in melanoma cell lines. Acta biochimica Polonica 12 16505900
2023 Single-exonuclease nanocircuits reveal the RNA degradation dynamics of PNPase and demonstrate potential for RNA sequencing. Nature communications 11 36725855
2014 Blastocyst euploidy and implantation rates in a young (<35 years) and old (≥35 years) presumed fertile and infertile patient population. Fertility and sterility 11 25154676
2013 Identification of genes potentially regulated by human polynucleotide phosphorylase (hPNPase old-35) using melanoma as a model. PloS one 11 24143183
2007 Activation of double-stranded RNA dependent protein kinase, a new pathway by which human polynucleotide phosphorylase (hPNPase(old-35)) induces apoptosis. Cancer research 11 17804700
2022 MiR-183-5p-PNPT1 Axis Enhances Cisplatin-induced Apoptosis in Bladder Cancer Cells. Current medical science 10 35788944
2023 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. NPJ biofilms and microbiomes 9 37286543
2022 SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer. International journal of molecular sciences 9 36232701
2022 Target recognition by RNase E RNA-binding domain AR2 drives sRNA decay in the absence of PNPase. Proceedings of the National Academy of Sciences of the United States of America 9 36409892
2021 Impact of PNPase on the transcriptome of Rhodobacter sphaeroides and its cooperation with RNase III and RNase E. BMC genomics 9 33549057
2018 Biochemical characterization of Campylobacter jejuni PNPase, an exoribonuclease important for bacterial pathogenicity. Biochimie 7 29339148
2009 Acute lymphoblastic leukemia-derived dendritic cells express tumor associated antigens: PNPT1, PMPCB, RHAMM, BSG and ERCC1. Neoplasma 7 19580345
2024 Mitochondrial sequencing identifies long noncoding RNA features that promote binding to PNPase. American journal of physiology. Cell physiology 6 38826135
2021 Crystallographic modeling of the PNPT1:c.1453A>G variant as a cause of mitochondrial dysfunction and autosomal recessive deafness; expanding the neuroimaging and clinical features. Mitochondrion 6 33812062
2024 Selective 8-oxo-rG stalling occurs in the catalytic core of polynucleotide phosphorylase (PNPase) during degradation. Proceedings of the National Academy of Sciences of the United States of America 5 39495922
2022 The absence of PNPase activity in Enterococcus faecalis results in alterations of the bacterial cell-wall but induces high proteolytic and adhesion activities. Gene 5 35609794
2020 PNPT1 and PCGF3 variants associated with angiotensin-converting enzyme inhibitor-induced cough: a nested case-control genome-wide study. Pharmacogenomics 5 32397904
2012 Crystallization and preliminary X-ray diffraction studies of Xanthomonas campestris PNPase in the presence of c-di-GMP. Acta crystallographica. Section F, Structural biology and crystallization communications 5 23027759
2023 Human PNPase causes RNA stabilization and accumulation of R-loops in the Escherichia coli model system. Scientific reports 4 37479726
2025 Structural insights into human PNPase in health and disease. Nucleic acids research 3 39997218
2013 Polynucleotide phosphorylase (PNPase) is required for Salmonella enterica serovar Typhimurium colonization in swine. Microbial pathogenesis 3 24126127
2024 Blockade of pan-viral propagation by inhibition of host cell PNPT1. International journal of antimicrobial agents 2 38412930
2025 A novel polyribonucleotide nucleotidyltransferase 1 (PNPT1) gene variant potentially associated with combined oxidative phosphorylation deficiency 13: case report and literature review. Translational pediatrics 1 40115456
2025 Loop-mediated regulation and base flipping drive RNA cleavage by human mitochondrial PNPase. Nucleic acids research 1 41361968
2024 Clinical Value of Circ-PNPT1 on Adverse Pregnancy Outcomes of Patients with Gestational Diabetes Mellitus. Endocrine, metabolic & immune disorders drug targets 1 36582066
2024 RNase R vs. PNPase: selecting the best-suited exoribonuclease for environmental adaptation. Extremophiles : life under extreme conditions 1 39052080
2024 Unravelling Heterogeneity: A Rare PNPT1 Variant in Childhood-Onset Spinocerebellar Ataxia with Sensorineural Hearing Loss. Cerebellum (London, England) 1 39729134
2024 PNPT1 Spectrum Disorders: An Underrecognized and Complex Group of Neurometabolic Disorders. Muscles (Basel, Switzerland) 1 40757543
2023 Structure and function of Campylobacter jejuni polynucleotide phosphorylase (PNPase): Insights into the role of this RNase in pathogenicity. Biochimie 1 37806617
2013 Ring around the Ro-sie: RNA-mediated alterations of PNPase activity. Cell 1 23540686
2025 A Preliminary Study of circ-PNPT1/miR-144-3p/UBE2G1 Expression in Placental Tissues and Serum and Its Mechanism in Patients With Gestational Diabetes Mellitus. Molecular reproduction and development 0 40996425
2024 Pathological PNPase variants with altered RNA binding and degradation activity affect the phenotype of bacterial and human cell models. NAR molecular medicine 0 41255389
2023 Lack of PNPase activity in Enterococcus faecalis 14 increases the stability of EntDD14 bacteriocin transcripts. Scientific reports 0 38129448
2022 [Role of PNPT1 in cardiomyocyte apoptosis induced by oxygen-glucose deprivation]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 35527495

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