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FLASH GENE
Symbol PARN contributors: mct/npt - updated : 19-10-2018
HGNC name poly(A)-specific ribonuclease (deadenylation nuclease)
HGNC id 8609
Corresponding disease
DKCB6 dyskeratosis congenita, autosomal recessive 6
Location 16p13.12      Physical location : 14.529.558 - 14.724.124
Synonym name
  • deadenylation nuclease
  • Aspecific ribonuclease PARN
    • Synonym symbol(s) DAN, Poly
    EC.number 3.1.13.4
    DNA
    TYPE functioning gene
    STRUCTURE 194.60 kb     24 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - HERC2P4 - D16F37S6 - PARN /D15S543 - qter
    Authors Buiting (99)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    24 - 3000 - 578 - Zhang (2007)
    23 - 2945 - 593 - -
    24 - 3083 73.4 639 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   highly
    Endocrinethyroid   highly
    Lymphoid/Immunethymus   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a catalytic domain
  • three RNA-binding domains (the nuclease, R3H and RRM domains); compared to the RRM domain, the R3H domain played a more important role in the structural integrity of the dimeric PARN
  • a C-terminal domain
    • HOMOLOGY
    intraspecies homolog to PNLDC1
    Homologene
    FAMILY
  • Rnase D family of 3' exoribonucleases
  • CAF1 family
    • CATEGORY enzyme , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,ribosome
    intracellular,nucleus,nucleolus
    intracellular,nuclear envelope
    text not stably associated to ribosomes
    basic FUNCTION
  • poly A specific exoribonuclease, deadenylation nuclease, degrading poly A tail of mRNA molecules
  • intrinsic cap binding activity
  • key enzyme in eukaryotic organisms to regulate the stability of mRNA by degrading the 3' poly-(A) tail
  • PARN participates in diverse and important intracellular processes by acting as a regulator of mRNA stability and translational efficiency
  • PARN modulates decay of a defined set of mRNAs in mammalian cells and implicate this deadenylase in coordinating control of genes required for cell movement
  • PARN is a divalent metal-ion dependent poly(A)-specific, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades poly(A) tails of eukaryotic mRNAs
  • PARN participates in diverse physiological processes by regulating mRNA fates through deadenylation
  • self-association may likely facilitate PARN to concentrate around the target mRNAs by restricted diffusion
  • new role for PARN in the biogenesis of TERC, providing a mechanism linking PARN mutations to telomere diseases
  • PNLDC1 shows limited conservation compared to PARN and represents an evolutionary related but distinct group of enzymes
  • PARN and TOE1 are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases
    • CELLULAR PROCESS protein, translation/synthesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with the cleavage and polyadenylation specific factors CPSF1, CPSF2, CPSF3, CPSF4, CPSF5, CPSF6 and CSTF3
  • PARN is part of the enzymatic machinery that matures the human 18S ribosomal RNA (rRNA)
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • iron Fe2+
    • protein
  • interacting with NCBP1, potential regulator of PARN
  • PARN increased TERC levels by deadenylating TERC, thereby limiting its degradation by EXOSC10
  • PARN downregulates PLD2 whereas PLD2 upregulates PARN
  • ELAVL1 and PARN destabilize Cat2 transcribed nuclear RNA (Ctn RNA) in absence of ADARB1, indicating that ADAR2 stabilizes Ctn RNA by antagonizing its degradation by PARN and ELAVL1
  • NCL phosphorylation offers specificity to its protein-protein, protein-RNA interactions, resulting in the PARN deadenylase regulation, and hence gene expression, during cellular stress responses
    • cell & other
    REGULATION
    activated by stimulated by the presence of an m(7)-guanine cap on substrate RNAs
    ASSOCIATED DISORDERS
    corresponding disease(s) DKCB6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    PARN deficiency leads to human telomerase RNA instability
    tumoral     --over  
    increased levels of PARN and NOCT correlate with significantly increased survival in squamous cell lung cancer
    Susceptibility
  • to idiopathic pulmonary fibrosis (IPF)
    • Variant & Polymorphism other
  • mutation carriers had shortened leukocyte telomere lengths, and explain ~7p100 of familial pulmonary fibrosis
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS