Affinage

PARN

Poly(A)-specific ribonuclease PARN · UniProt O95453

Length
639 aa
Mass
73.5 kDa
Annotated
2026-06-10
56 papers in source corpus 29 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

PARN is a divalent metal ion-dependent, poly(A)-specific 3'-to-5' exoribonuclease that controls the stability and 3'-end maturation of both mRNAs and small noncoding RNAs (PMID:16281054, PMID:11424938, PMID:22442037). Structurally it functions as an obligate homodimer in which the R3H domain of one subunit partially encloses the catalytic site of the other, and disrupting dimerization abolishes both nuclease and RNA-binding activity (PMID:16281054); the enzyme can further self-associate into tetramers and higher-order oligomers that enhance catalytic processivity (PMID:25239613). PARN simultaneously engages the substrate 3' poly(A) tail and the mRNA 5' cap, and cap binding amplifies its processive deadenylation (PMID:16281054, PMID:26772900, PMID:15653638). In the nucleolus and Cajal bodies, PARN performs maturation trimming by removing oligo(A) tails that the noncanonical poly(A) polymerase PAPD5 adds to H/ACA box snoRNAs, scaRNAs, the telomerase RNA TERC/hTR, and Y RNAs; without PARN these oligoadenylated species are diverted to exonucleolytic destruction by EXOSC10/RRP6 or DIS3L/DIS3L2, so PARN stabilizes these RNAs by preventing their degradation (PMID:22442037, PMID:26482878, PMID:26950371, PMID:28760775, PMID:30575725). Through analogous removal of PAPD5-added oligo(A) tails, PARN also destabilizes specific miRNAs, including a set that represses p53 translation, so that PARN loss elevates p53 in a Dicer-dependent manner (PMID:30770239). PARN substrate selection is directed by RNA-binding cofactors—CUGBP1, nucleolin, Ago2-miRISC, PTBP1, and CPSF6—that recruit it to defined transcripts such as c-fos, TNFα, miR-122, and TP53 mRNA (PMID:16601207, PMID:26130707, PMID:26400160, PMID:29168431, PMID:39297407, PMID:41825960), and its activity is gated by phosphorylation, including DNA-damage/MK2-driven Ser557 phosphorylation that switches its localization and partner selection between the nucleolus, ER, and cytosol (PMID:31387300, PMID:31936572). Biallelic PARN mutations reduce deadenylase activity, shorten telomeres, and perturb snoRNA processing and ribosome biogenesis, with effects on hematopoiesis and embryonic development (PMID:26342108, PMID:31273937).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Established that PARN is a poly(A)-specific 3' exonuclease whose poly(A) binding contributes to substrate specificity and that can act in the nucleus, defining the basic enzymatic identity.

    Evidence Protein purification, in vitro deadenylation, and Xenopus oocyte microinjection of xPARN

    PMID:11424938

    Open questions at the time
    • Structural basis of poly(A) recognition not yet resolved
    • Human enzyme regulation not addressed
  2. 2005 High

    Resolved how PARN catalysis works structurally, showing the active unit is a homodimer in which the R3H domain of one subunit engages the partner active site and cap binding amplifies processivity.

    Evidence X-ray crystallography of free and RNA-bound truncated human PARN plus dimerization-disrupting mutagenesis

    PMID:16281054

    Open questions at the time
    • C-terminal domain absent from crystallized construct
    • Cap-binding domain mechanism not directly visualized
  3. 2006 High

    Answered how PARN is targeted to specific mRNAs, identifying CUGBP1 as the first RNA-binding protein that directly recruits a deadenylase to ARE-containing substrates.

    Evidence In vitro deadenylation, co-IP from extracts, and recombinant protein pulldown on c-fos/TNFα mRNAs

    PMID:16601207

    Open questions at the time
    • In vivo significance of CUGBP1 recruitment not established
    • Generality across other ARE mRNAs untested
  4. 2012 High

    Extended PARN's role from mRNA decay to noncoding RNA maturation, showing it trims PAPD5-added oligo(A) tails to complete 3'-end maturation of H/ACA snoRNAs and scaRNAs in nucleoli and Cajal bodies.

    Evidence siRNA knockdown with 3'-end deep sequencing, immunofluorescence, and PAPD5 epistasis; parallel mouse myoblast mRNA stability/migration study

    PMID:22442037 PMID:22956911

    Open questions at the time
    • Why C/D box snoRNAs are spared not explained
    • Direct enzyme-substrate kinetics in vivo not measured
  5. 2015 High

    Connected PARN to telomere biology and disease by showing it matures TERC by removing oligo(A) tails, with patient mutations reducing TERC and shortening telomeres while broadening the miRNA/mRNA targets directed by CUGBP1 and miRISC.

    Evidence TERC 3'-end sequencing in patient cells with complementation rescue; PARN/CUGBP1 reconstitution on miR-122; Ago2-PARN co-IP and TP53 3'-UTR reporters; patient cell activity assays with zebrafish/marrow knockdown

    PMID:26130707 PMID:26342108 PMID:26400160 PMID:26482878

    Open questions at the time
    • Causal chain from TERC defect to specific clinical phenotypes incompletely mapped
    • Several cofactor recruitment events from single labs
  6. 2016 High

    Defined the degradation pathways PARN protects against, showing PARN-mediated deadenylation of hTR limits PAPD5-EXOSC10 decay and decapping/XRN1 routes, and characterized the cap-binding mechanism biophysically.

    Evidence Multi-component knockdown epistasis (PAPD5, EXOSC10, DCP2, XRN1) with telomerase assays; SPR/fluorescence/CD cap-binding kinetics

    PMID:26772900 PMID:26950371

    Open questions at the time
    • Stoichiometry of competing decay enzymes in cells not quantified
    • Physiological cap forms engaged in vivo unclear
  7. 2017 Medium

    Broadened the noncoding RNA target set and revealed cofactor-controlled activation, establishing Y RNA stabilization via PAPD5/DIS3L and nucleolin phosphorylation as an activating switch for PARN.

    Evidence PARN/PAPD5/DIS3L knockdown epistasis with 3'-end sequencing; NCL-PARN co-IP and deadenylase assays with phospho-deficient NCL under UV stress

    PMID:28760775 PMID:29168431

    Open questions at the time
    • Single-lab findings without reciprocal validation
    • Kinase responsible for NCL phosphorylation in this context not pinned down
  8. 2018 High

    Clarified the division of labor among nuclear trimming enzymes, showing PARN acts redundantly with TOE1 on scaRNAs/TERC and works downstream of RRP6 in a two-step TERC processing pathway guided by H/ACA RNP assembly.

    Evidence PARN/TOE1 double knockdown with mTAIL-seq and snRNA pseudouridylation; in vitro processing with purified PARN and RRP6 plus RNP assembly and structure probing

    PMID:29669292 PMID:30575725

    Open questions at the time
    • Determinants partitioning a precursor to processing vs degradation only partly defined
    • Redundancy quantification incomplete
  9. 2019 Medium

    Linked PARN to p53 control and organismal phenotypes, showing it destabilizes p53-repressing miRNAs via DIS3L/DIS3L2, that a phospho-mimic C-terminal switch reshapes nucleolar partner selection, and that PARN loss impairs rRNA biogenesis with embryonic lethality in mice.

    Evidence PARN/PAPD5/DIS3L/DIS3L2 knockdown with miRNA sequencing and Dicer-dependence; S557D mutagenesis with CTD spectroscopy, imaging, and CBP80/CstF-50 co-IP; patient fibroblasts, heterozygous and homozygous Parn KO mice

    PMID:30770239 PMID:31273937 PMID:31387300

    Open questions at the time
    • Some mechanistic links inferred from expression data
    • Identity of the S557 kinase under DNA damage not defined here
  10. 2020 Medium

    Revealed compartmentalized PARN function, showing ER-anchored PARN shapes ER-associated transcript poly(A) profiles and that MK2 phosphorylation of Ser557 drives its DNA-damage relocalization from ER to cytosol.

    Evidence Subcellular fractionation, liposome insertion of purified PARN, ER-anchored constructs, ER-RNA transcriptomics, and MK2 phosphorylation assay

    PMID:31936572

    Open questions at the time
    • Single-lab study; mechanism of ER anchoring partly inferred
    • Generality of ER pool beyond tested transcripts unknown
  11. 2023 Medium

    Demonstrated a disease-relevant feedforward circuit, with PARN sustaining EGFR by degrading miR-7 to drive STAT3-dependent PARN expression and tumor infiltration in glioblastoma stem cells.

    Evidence PARN knockdown, miR-7/EGFR/STAT3 assays, and orthotopic xenograft survival with STAT3 inhibition

    PMID:37747775

    Open questions at the time
    • Directness of PARN action on miR-7 vs indirect effects not fully separated
    • Single tumor model
  12. 2024 Medium

    Extended PARN to metabolic physiology, showing it partners with PTBP1 to regulate Slc30a8/Chst3 mRNA stability and is required for glucose-stimulated insulin secretion.

    Evidence β-cell conditional Parn KO mice, PARN-PTBP1 co-IP, LACE-seq, and GSIS assays

    PMID:39297407

    Open questions at the time
    • Whether deadenylation per se underlies the secretion phenotype not fully isolated
    • Single lab
  13. 2026 Medium

    Showed PARN acts on poly(A) site choice and miRNA biogenesis in vivo, promoting proximal poly(A) usage and Foxp1 destabilization in B cells, and forming a mutual feedback loop with miR-29a/miR-1207 via CPSF6 recruitment.

    Evidence Conditional B-cell Parn KO with genome-wide poly(A) sequencing and antibody assays; PARN/CPSF6 co-IP, pri-miRNA RIP, and PARN 3'-UTR reporters with migration assays

    PMID:41825960 PMID:42118147

    Open questions at the time
    • Mechanism coupling deadenylation to poly(A) site selection unresolved
    • Single-lab findings awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many cofactor-recruitment and phosphorylation inputs are integrated to direct PARN between its mRNA-decay, ncRNA-maturation, and compartment-specific functions in a given cell state remains unresolved.
  • No unified model integrating cofactor selection with localization switching
  • Quantitative substrate hierarchy in vivo not established
  • Kinase network controlling PARN phosphosites incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0140098 catalytic activity, acting on RNA 6 GO:0016787 hydrolase activity 3
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 2 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
AGO2CBP80CPSF6CUGBP1DKC1NCLPAPD5PTBP1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Crystal structure of C-terminal truncated human PARN in free and RNA-bound forms reveals a homodimer with an R3H domain and a nuclease domain; the R3H domain of one subunit partially encloses the active site of the other, poly(A) binds in a deep cavity in a sequence-nonspecific manner, and mutations disrupting dimerization abolish both enzymatic and RNA-binding activities, establishing the dimer as the structural and functional unit. The cap-binding domain acts with the R3H domain to amplify processivity. X-ray crystallography (free and RNA-bound forms) combined with dimerization-disrupting mutagenesis and enzymatic activity assays The EMBO journal High 16281054
2001 Xenopus PARN (xPARN) is a poly(A)-specific 3' exonuclease that copurifies as 62 kDa and 74 kDa polypeptides (the 62 kDa being a proteolytic product). It contains a tripartite exonuclease domain, a putative RNA recognition motif, and an MCM-like domain. It can be activated in the oocyte nucleus independently of cytoplasmic components, and nuclear export of deadenylated RNA is impeded. The enzyme binds poly(A) in the absence of catalysis, contributing to substrate specificity. Protein purification, molecular cloning, in vitro deadenylation assay, microinjection into Xenopus oocytes, western blot RNA (New York, N.Y.) High 11424938
2006 CUG-BP (CUGBP1) binds ARE-containing mRNAs (c-fos, TNFα) and directly recruits PARN deadenylase to stimulate poly(A) shortening. CUG-BP interacts with PARN in cell extracts by co-immunoprecipitation, and this interaction is recapitulated with recombinant proteins, identifying CUG-BP as the first RNA-binding protein shown to directly recruit a deadenylase to an RNA substrate. In vitro deadenylation assay, co-immunoprecipitation from extracts, recombinant protein pulldown RNA (New York, N.Y.) High 16601207
2012 PARN knockdown in human cells causes accumulation of oligoadenylated processing intermediates of H/ACA box snoRNAs and scaRNAs (but not C/D box RNAs). PARN is concentrated in nucleoli and Cajal bodies. The non-canonical poly(A) polymerase PAPD5 adds oligo(A) tails to snoRNA 3' stubs, and PARN removes these tails to complete 3' end maturation, coupling deadenylation to clean trimming and snoRNA stabilization. siRNA knockdown, deep sequencing of RNA 3' ends, immunofluorescence localization, PAPD5 knockdown epistasis RNA (New York, N.Y.) High 22442037
2015 PARN is required for 3'-end maturation of the telomerase RNA component (TERC). Patient-derived cells with PARN mutations show decreased TERC levels and increased oligo(A)-tailed forms of TERC. Deep sequencing demonstrates that PARN removes post-transcriptionally acquired oligo(A) tails that target TERC for nuclear degradation. Restoring PARN normalizes TERC levels and the proportion of oligo(A) forms. Deep sequencing of TERC 3' ends in patient-derived somatic cells and iPSCs, PARN complementation rescue, PARN disruption in immortalized cells Nature genetics High 26482878
2016 PARN increases human telomerase RNA (hTR) levels by deadenylating hTR, thereby limiting its degradation by EXOSC10 (which is recruited following PAPD5-mediated oligoadenylation). Defects in dyskerin binding lead to hTR degradation via PAPD5 oligoadenylation → EXOSC10 3'-to-5' decay, as well as decapping by DCP2 and 5'-to-3' decay by XRN1. Knockdown of DCP2 and/or EXOSC10 rescues telomerase activity and hTR localization in PARN-deficient cells. Knockdown epistasis (PARN, PAPD5, EXOSC10, DCP2, XRN1), hTR level and localization measurements, telomerase activity assays Nature structural & molecular biology High 26950371
2015 PARN deadenylase activity is required for deadenylation of miR-122 in human cells; PARN knockdown leads to accumulation of 3'-oligoadenylated miR-122 and increased miR-122 stability. CUGBP1 specifically interacts with miR-122 and other UG-rich miRNAs, interacts directly with PARN, and recruits PARN to miR-122 to enhance PARN-mediated deadenylation and degradation in a dose-dependent manner in vitro. PARN knockdown, deep sequencing of miRNA 3' ends, in vitro deadenylation assay with CUGBP1, PARN/CUGBP1 co-immunoprecipitation Nucleic acids research High 26130707
2019 PARN regulates the levels of numerous miRNAs by removing oligo(A) tails added by PAPD5; remaining oligo(A) tails recruit the exonucleases DIS3L or DIS3L2 to degrade the miRNA. PARN knockdown destabilizes multiple miRNAs that repress p53 translation, leading to p53 accumulation in a Dicer-dependent manner, explaining the p53 elevation in PARN-defective patients. PARN/PAPD5/DIS3L/DIS3L2 knockdown epistasis, miRNA 3'-end sequencing, p53 protein measurement, Dicer-dependence experiment Molecular cell High 30770239
2017 PARN depletion reduces levels of abundant human Y RNAs. PAPD5 depletion or DIS3L knockdown rescues the effect of PARN depletion on Y RNA levels, establishing that PARN stabilizes Y RNAs by removing PAPD5-added oligoadenylated tails that otherwise recruit DIS3L for degradation. PARN also deadenylates U6 and RMRP RNAs without affecting their levels. PARN/PAPD5/DIS3L knockdown epistasis, deep sequencing of RNA 3' ends Molecular and cellular biology High 28760775
2018 PARN and TOE1 act redundantly on small Cajal body-specific RNAs (scaRNAs) and on TERC biogenesis. Combined depletion of PARN and TOE1 strongly downregulates scaRNAs, leading to defects in snRNA pseudouridylation. Neither enzyme alone targets mRNA poly(A) tails; their substrates are nuclear small ncRNAs. mTAIL-seq, RNA-seq, double knockdown of PARN and TOE1, snRNA pseudouridylation assay Cell reports High 29669292
2018 TERC precursor processing by PARN and RRP6 occurs in two steps: longer 3'-extended precursors are first trimmed by RRP6, then shorter forms are processed by PARN. H/ACA RNP assembly actively promotes productive processing and protects the mature 3' end; tertiary RNA interactions in longer transcripts favor degradation over processing. In vitro RNA processing assays with purified PARN and RRP6, H/ACA RNP assembly assays, RNA structure probing Nature communications High 30575725
2016 In C. elegans, PARN-1 (the PARN ortholog) trims piRNA 3' ends; PARN-1-deficient animals accumulate untrimmed piRNAs with 3' extensions. Longer piRNAs associate with the Piwi protein PRG-1 but fail to robustly recruit downstream silencing factors, demonstrating that precise piRNA length determined by PARN-1 is required for efficient transcriptome surveillance. PARN-1 loss-of-function genetics in C. elegans, deep sequencing of piRNAs, PRG-1 co-immunoprecipitation, silencing factor recruitment assay Cell High 26919432
2015 Cells from patients with biallelic PARN mutations have severely reduced PARN deadenylation activity and impaired oligoadenylation of specific H/ACA box snoRNAs. PARN-deficient patient cells display short telomeres and aberrant ribosome profiles. Knockdown of PARN in human marrow cells and zebrafish impairs haematopoiesis. Biochemical deadenylation activity assay on patient cells, snoRNA oligoadenylation analysis, telomere length measurement, ribosome profile, PARN knockdown in human marrow cells and zebrafish morpholino experiments Journal of medical genetics Medium 26342108
2012 PARN knockdown in mouse myoblasts stabilizes a defined set of ~40 mRNAs including ZFP36L2, and increases Zfp36l2 poly(A) tail length and translation. The PARN-dependent regulatory elements reside in the 3' UTR. PARN knockdown also broadly affects gene expression, reducing levels of mRNAs encoding cell migration and adhesion factors; PARN-depleted cells migrate faster in wound-healing assays. Stable PARN knockdown, global mRNA half-life analysis, poly(A) tail length assay, 3' UTR reporter assay, wound-healing migration assay PLoS genetics Medium 22956911
2016 Molecular recognition of the mRNA 5' cap by PARN differs from other cap-binding proteins: PARN dimer subunits show negative cooperativity in cap binding; non-coulombic interactions dominate complex formation; and PARN has versatile activity toward alternative cap forms. Cap binding amplifies the processivity of PARN deadenylation. Surface plasmon resonance kinetics, quantitative equilibrium fluorescence titrations, circular dichroism Biochimica et biophysica acta Medium 26772900
2019 The intrinsically disordered C-terminal domain (CTD) of PARN contains nuclear and nucleolar localization signals. Phosphorylation-mimic mutation S557D disrupts local CTD structure and alters binding partner selection: under normal conditions nucleolus-residing PARN recruits CBP80 to repress deadenylase activity; DNA damage-induced phosphorylation of S557 expels CBP80 from nucleoli (releasing activity inhibition) and recruits CstF-50 into nucleoli to activate deadenylation. This function switch reshapes the profile of small nuclear ncRNAs in response to DNA damage. Mutagenesis (S557D phospho-mimic), spectroscopic analysis of CTD structure, fluorescence microscopy of protein localization, co-immunoprecipitation of CBP80 and CstF-50, ncRNA profiling Cells Medium 31387300
2015 PARN is a phosphoprotein and its phosphorylation state is modulated by serum status. Under serum deprivation, cap association by PARN increases while eIF4E cap occupancy decreases, suggesting a competition at the 5' cap regulated by post-translational phosphorylation of PARN that influences whether mRNA is translated or decayed. Cap-binding fractionation assay, phosphoprotein analysis, serum starvation treatment, reporter translation assay Nucleic acids research Medium 15653638
2015 PARN mediates miRNA-dependent degradation of TP53 mRNA. Argonaute-2 (Ago-2), the core component of miRISC, co-exists in complexes with PARN and activates its deadenylase activity. miR-125b-loaded miRISC recruits PARN to TP53 mRNA via both an ARE and an adjacent miR-125b/miR-504 targeting site in the 3' UTR; HuR can revert this recruitment. Co-immunoprecipitation of Ago-2 with PARN, in vitro deadenylase activity assay, 3' UTR reporter assays, PARN knockdown mRNA stability measurement Nucleic acids research Medium 26400160
2017 Nucleolin (NCL) phosphorylation at CK2 consensus sites is required to activate PARN deadenylase activity upon oncogenic stimuli and UV stress. NCL interacts directly with PARN and, under non-stress conditions, forms complexes with p53 and HuR. Phosphorylation-deficient NCL (NCL-6/S*A) cannot activate PARN, and hypophosphorylated NCL favors interactions with HuR and p53. NCL interacts with PARN substrate mRNAs including TP53 and BCL2. Co-immunoprecipitation of NCL with PARN, deadenylase activity assay with WT vs. phospho-deficient NCL, UV stress treatment, mRNA stability measurement RNA biology Medium 29168431
2014 PARN can self-associate into tetramers and higher-order oligomers both in vitro and in living cells. Self-association is triggered by the R3H domain, which causes burial of Trp219 in a solvent-inaccessible environment. The RRM and C-terminal domains modulate the dissociation rate of tetrameric PARN. Tetramerization significantly enhances the catalytic activity and processivity of the truncated form lacking the RRM and C-terminal domains. Analytical ultracentrifugation/size-exclusion chromatography for oligomerization, site-directed mutagenesis of R3H domain, tryptophan fluorescence spectroscopy, in vitro deadenylase activity assay of truncations Biochimica et biophysica acta Medium 25239613
2019 PARN deficiency compromises ribosomal RNA biogenesis in patient fibroblasts and heterozygous Parn knockout mice. PARN deficiency down-regulates shelterin transcripts (TRF1, TRF2, TPP1, RAP1, POT1) and DKC1 mRNA (the latter through p53 activation). Homozygous Parn KO causes early embryonic lethality not rescued by p53 KO. Patient fibroblast analysis, inducible PARN KO and complementation cell line, heterozygous Parn KO mice, rRNA biogenesis assay, RT-qPCR for shelterin transcripts, double Parn/p53 KO EMBO molecular medicine Medium 31273937
2020 PARN is anchored to the endoplasmic reticulum (ER) surface where it reshapes the poly(A) length profile of ER-associated RNAs by suppressing long poly(A) tails. ER-anchored PARN triggers degradation of a subset of ER-enriched transcripts including MDM2, modulating DNA damage response and cell viability. MK2 kinase phosphorylates PARN-Ser557 during DNA damage to promote PARN translocation from the ER to the cytosol. Subcellular fractionation, liposome insertion assay with purified PARN, ER-anchored PARN expression constructs, transcriptome sequencing of ER-associated RNAs, MK2 kinase phosphorylation assay, poly(A) tail length analysis Cells Medium 31936572
2009 Synthetic fluoro-pyranosyl nucleoside analogues (cytosine- and adenine-based) competitively inhibit human PARN at its active site. Kinetic analysis shows the inhibition is competitive and cannot be released by altering Mg²⁺ concentration. Molecular docking indicates the sugar moiety stabilizes the compounds in the active site through interactions with catalytic residues. In vitro PARN deadenylase activity kinetic analysis, molecular docking and molecular dynamics simulation Biochemistry Medium 19472977
2011 Novel uracil-based glucopyranosyl nucleoside analogues (including U1) inhibit human PARN via slow-binding, slow-release competitive inhibition at the active site, with Ki values in the low µM range (11–33-fold lower than previously reported adenosine/cytosine analogues). Molecular docking confirms binding at the PARN active site. In vitro kinetic analysis (slow-binding inhibition kinetics), molecular docking Biochimie Medium 22041582
2009 Purine nucleotides inhibit human PARN in vitro: RTP nucleotides act as non-competitive inhibitors, while RDP and RMP exhibit competitive inhibition. Mg²⁺ can release inhibition by RTP and RDP but not RMP. In vitro PARN deadenylase activity kinetic analysis with varied Mg²⁺ Journal of enzyme inhibition and medicinal chemistry Medium 18763168
2024 PARN interacts with polypyrimidine tract-binding protein 1 (PTBP1) in pancreatic β cells, co-regulating the RNA stability of Slc30a8 and Chst3 mRNAs. PARN deficiency in β cells impairs glucose-stimulated insulin secretion (GSIS) and insulin maturation; conditional PARN knockout mice show reduced GSIS without altered β-cell development or insulin sensitivity. β-cell-specific conditional Parn KO mice, co-immunoprecipitation of PARN with PTBP1, LACE-seq for RNA-protein interactions, NIT-1 cell knockdown, glucose-stimulated insulin secretion assay, transcriptomics Advanced science Medium 39297407
2023 In glioblastoma stem cells, PARN positively regulates EGFR expression by negatively regulating the EGFR-targeting miRNA miR-7 through its 3'-5' exoribonuclease activity. Increased EGFR then creates a positive feedback loop activating STAT3, which transcriptionally drives PARN expression. PARN depletion in GSCs reduces tumor infiltration and prolongs survival in orthotopic xenografts. PARN knockdown (siRNA, shRNA), miR-7 level measurement, EGFR/STAT3 signaling assays, orthotopic brain tumor xenograft survival, pharmacological STAT3 inhibition, siRNA nanocapsule delivery Cancer research Medium 37747775
2026 PARN binds 3' UTRs and promotes utilization of proximal poly(A) sites genome-wide in B cells in vivo, binding UGUA and AA(U/A)AAA upstream elements to form a specific spatial RNA-protein complex. Through its exonuclease activity, PARN shortens poly(A) tails to decrease mRNA stability of targets including Foxp1, thereby promoting antibody secretion and class switch recombination. Conditional B-cell PARN knockout, genome-wide poly(A) site sequencing, RNA immunoprecipitation for binding elements, poly(A) tail length analysis, antibody secretion assay Advanced science Medium 42118147
2026 PARN associates with pri-miR-29a and pri-miR-1207 and regulates their poly(A) tail lengths. CPSF6 recruits PARN to pri-miRNAs, and together they affect primary and mature miR-29a-3p levels. miR-29a-3p and miR-1207-5p in turn bind the 3' UTR of PARN mRNA to regulate its expression, establishing a mutual feedback regulatory loop. Modulation of PARN, miR-29a-3p, or miR-1207-5p expression affects cell migration. RNA immunoprecipitation of PARN with pri-miRNAs, CPSF6 co-immunoprecipitation, 3' UTR reporter for PARN mRNA, miRNA 3'-end sequencing, migration assay Life science alliance Medium 41825960

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nature genetics 383 25848748
2015 Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component. Nature genetics 156 26482878
2006 CUG-BP binds to RNA substrates and recruits PARN deadenylase. RNA (New York, N.Y.) 153 16601207
2012 Maturation of mammalian H/ACA box snoRNAs: PAPD5-dependent adenylation and PARN-dependent trimming. RNA (New York, N.Y.) 134 22442037
2016 The RNase PARN-1 Trims piRNA 3' Ends to Promote Transcriptome Surveillance in C. elegans. Cell 118 26919432
2016 Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects. Nature structural & molecular biology 103 26950371
2005 Structural insight into poly(A) binding and catalytic mechanism of human PARN. The EMBO journal 99 16281054
2001 The mechanism and regulation of deadenylation: identification and characterization of Xenopus PARN. RNA (New York, N.Y.) 88 11424938
2015 Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN). Journal of medical genetics 85 26342108
2004 mRNA deadenylation by PARN is essential for embryogenesis in higher plants. RNA (New York, N.Y.) 74 15247430
2018 PARN and TOE1 Constitute a 3' End Maturation Module for Nuclear Non-coding RNAs. Cell reports 69 29669292
2015 Destabilization of microRNAs in human cells by 3' deadenylation mediated by PARN and CUGBP1. Nucleic acids research 65 26130707
2019 The RNase PARN Controls the Levels of Specific miRNAs that Contribute to p53 Regulation. Molecular cell 63 30770239
2013 Poly(A)-specific ribonuclease (PARN): an allosterically regulated, processive and mRNA cap-interacting deadenylase. Critical reviews in biochemistry and molecular biology 60 23496118
2012 The PARN deadenylase targets a discrete set of mRNAs for decay and regulates cell motility in mouse myoblasts. PLoS genetics 48 22956911
2015 PARN deadenylase is involved in miRNA-dependent degradation of TP53 mRNA in mammalian cells. Nucleic acids research 43 26400160
2018 The H/ACA complex disrupts triplex in hTR precursor to permit processing by RRP6 and PARN. Nature communications 42 30575725
2005 Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability. Nucleic acids research 42 15653638
2019 Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models. EMBO molecular medicine 41 31273937
2012 Kiss your tail goodbye: the role of PARN, Nocturnin, and Angel deadenylases in mRNA biology. Biochimica et biophysica acta 38 23274303
2015 Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up. Pediatric neurology 35 26810774
2017 PARN Modulates Y RNA Stability and Its 3'-End Formation. Molecular and cellular biology 32 28760775
2014 Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression. Biochimica et biophysica acta 30 25499764
2017 Nucleolin phosphorylation regulates PARN deadenylase activity during cellular stress response. RNA biology 29 29168431
2012 Modulation of poly(A)-specific ribonuclease (PARN): current knowledge and perspectives. Current medicinal chemistry 29 22834816
2009 Competitive inhibition of human poly(A)-specific ribonuclease (PARN) by synthetic fluoro-pyranosyl nucleosides. Biochemistry 28 19472977
2019 From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants. Human mutation 24 31448843
2023 Cross-talk between PARN and EGFR-STAT3 Signaling Facilitates Self-Renewal and Proliferation of Glioblastoma Stem Cells. Cancer research 22 37747775
2011 PolyA-specific ribonuclease (PARN-1) function in stage-specific mRNA turnover in Trypanosoma brucei. Eukaryotic cell 18 21743004
2011 Kinetic and in silico analysis of the slow-binding inhibition of human poly(A)-specific ribonuclease (PARN) by novel nucleoside analogues. Biochimie 16 22041582
1999 The human gene for the poly(A)-specific ribonuclease (PARN) maps to 16p13 and has a truncated copy in the Prader-Willi/Angelman syndrome region on 15q11-->q13. Cytogenetics and cell genetics 15 10640832
2023 The PARN, TOE1, and USB1 RNA deadenylases and their roles in non-coding RNA regulation. The Journal of biological chemistry 14 37544646
2006 Expression and purification of recombinant poly(A)-specific ribonuclease (PARN). International journal of biological macromolecules 14 16620953
2021 Poly (A)-specific ribonuclease (PARN): More than just "mRNA stock clearing". Life sciences 13 34520768
2020 Multiple bilateral hip fractures in a patient with dyskeratosis congenita caused by a novel mutation in the PARN gene. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 13 33244623
2014 Self-association of poly(A)-specific ribonuclease (PARN) triggered by the R3H domain. Biochimica et biophysica acta 12 25239613
2009 Inhibition of human poly(A)-specific ribonuclease (PARN) by purine nucleotides: kinetic analysis. Journal of enzyme inhibition and medicinal chemistry 12 18763168
2020 CD8+ T-cell senescence and skewed lymphocyte subsets in young Dyskeratosis Congenita patients with PARN and DKC1 mutations. Journal of clinical laboratory analysis 11 32452087
2019 The Intrinsically Disordered C-Terminal Domain Triggers Nucleolar Localization and Function Switch of PARN in Response to DNA Damage. Cells 9 31387300
2017 A feedback mechanism between PLD and deadenylase PARN for the shortening of eukaryotic poly(A) mRNA tails that is deregulated in cancer cells. Biology open 8 28011629
2020 Translation Efficiency and Degradation of ER-Associated mRNAs Modulated by ER-Anchored poly(A)-Specific Ribonuclease (PARN). Cells 7 31936572
2024 PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 39297407
2019 Contributions of the C-terminal domain to poly(A)-specific ribonuclease (PARN) stability and self-association. Biochemistry and biophysics reports 4 30949591
2016 Molecular recognition of mRNA 5' cap by 3' poly(A)-specific ribonuclease (PARN) differs from interactions known for other cap-binding proteins. Biochimica et biophysica acta 4 26772900
2024 Hoyeraal-Hreidarsson syndrome: a case report of dyskeratosis congenita with a novel PARN gene mutation. Annals of medicine and surgery (2012) 3 39649862
2017 [A rare familial form of idiopathic pulmonary fibrosis with Poly(A)-specific ribonuclease (PARN) mutation]. Revue de pneumologie clinique 3 29055513
2025 RNA Analysis Uncovers Pathogenic PARN Variant in Dyskeratosis Congenita. Clinical genetics 2 40859110
2025 Optical Genomic Mapping and Next-Generation Sequencing Identified Retrotransposon Insertion and Missense Variant Disrupting PARN Gene in Dyskeratosis Congenita. Human mutation 2 40896794
2024 Chemical composition and biological activities of essential oil of the Malaysian endemic Syzygium variolosum (King) Chantar. & J.Parn. Natural product research 2 38766974
2022 PARN Knockdown in Cell Lines Results in Differential and Cell-Specific Alterations in the Expression of Cancer-Associated mRNAs. Asian Pacific journal of cancer prevention : APJCP 2 35092390
2025 Germline PARN Variants in Telomere Biology Disorders and Challenges in Variant Curation. Molecular genetics & genomic medicine 1 40438983
2023 Identification of PARN nuclease activity inhibitors by computational-based docking and high-throughput screening. Scientific reports 1 37002320
2026 MAT2A enhances PARN transcription via SRF to accelerate glycolysis and drive malignant progression in osteosarcoma. Communications biology 0 41530371
2026 Monoallelic PARN mutation presenting as pancytopenia, hepatic fibrosis and idiopathic pulmonary fibrosis. BMJ case reports 0 41741124
2026 Mutual feedback regulation between Poly(A)-specific ribonuclease (PARN) and cognate microRNAs. Life science alliance 0 41825960
2026 The RNA-Binding Protein PARN Remodeled 3' UTR Structure Defines Poly(A)-Loading Sites to Mediate Immunoglobulin Homeostasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42118147

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