The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PARN  -  poly(A)-specific ribonuclease

Homo sapiens

Synonyms: DAN, Deadenylating nuclease, Deadenylation nuclease, Poly(A)-specific ribonuclease PARN, Polyadenylate-specific ribonuclease
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PARN

  • We conclude that the four conserved acidic amino acids are essential residues of the PARN active site and that the active site of PARN functionally and structurally resembles the active site for 3'-exonuclease domain of Escherichia coli DNA polymerase I [1].
  • 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 [2].
  • Stimulation was observed with each of the three types of tumor cells used: LX-1 lung carcinoma, DAN pancreatic carcinoma, and TRIG melanoma [3].
  • In the present study, we have examined a biological role(s) of DAN in the regulation of RA-mediated cellular differentiation in neuroblastoma cells [4].

High impact information on PARN

  • Some of the KH motifs (KHs) of KSRP directly mediate RNA binding, mRNA decay, and interactions with the exosome and poly(A) ribonuclease (PARN) [5].
  • Several observations suggest that cap-DAN interactions are functionally important for the networking between regulated mRNA stability and translation [6].
  • Mutations disrupting dimerization abolish both the enzymatic and RNA-binding activities, suggesting that the PARN dimer is a structural and functional unit [7].
  • These data provide additional evidence that PARN is responsible for deadenylation during oocyte maturation and suggest that interactions between 5' cap and 3' poly(A) tail may integrate translational efficiency with mRNA stability [8].
  • Known cap-binding proteins, such as eIF4E and the nuclear cap-binding complex, are not detectable in the enzyme preparation, and PARN itself binds to m(7)GTP-Sepharose and is eluted specifically with the cap analog m(7)GTP [8].

Biological context of PARN

  • Based on our data we discuss binding and coordination of divalent metal ions in the active site of PARN [9].
  • By DNA sequence analysis of cDNA and genomic clones, fluorescence in situ hybridization, and reverse transcriptase-PCR, we have determined that the active human PARN gene is located in 16p13 and that a truncated copy lacking the 5' end is located in 15q11 [2].
  • 2. Although PARN and F37 gene sequences are present on 15q and 16p, our data suggest that the synteny of these loci is the result of independent genetic events [2].
  • Taken together, these data are consistent with a natural competition existing at the 5' cap structure between PARN and eIF4E that may be regulated by changes in post-translational modifications [10].
  • The amino acid sequence of DAN shows homology to the RNase D family of 3'-exonucleases [11].

Anatomical context of PARN

  • Here we report that deadenylation in HeLa cell extracts and by a purified mammalian poly(A)-specific exoribonuclease, PARN (previously designated deadenylating nuclease, DAN), is stimulated by the presence of an m(7)-guanosine cap on substrate RNAs [8].
  • Hybridization data with DAN from the infected cells demonstrated the presence of similar levels of viral sequences and the mutations in each of the MX-infected cell lines [12].
  • The forced expression of DAN gene enhanced the neurite extension in the presence of RA, suggesting that DAN gene product might contain some regulatory role(s) in the RA-induced cellular differentiation in neuroblastoma cells [4].

Associations of PARN with chemical compounds

  • Interestingly, adenosine dinucleotide (A) was efficiently hydrolyzed in the presence of Mn2+, Zn2+, or Co2+, suggesting that the substrate length requirement for PARN can be modulated by the identity of the divalent metal ion [9].
  • Furthermore, we show that the apparent dissociation constant ((app)K(d)) values for Fe(2+) binding at both sites were affected in PARN polypeptides in which the conserved acidic amino acid residues were substituted to alanine [1].
  • We have studied how the m7G(5')ppp(5')G cap structure affects the activity of PARN [13].
  • We have used iron(II)-induced hydroxyl radical cleavage to map Fe(2+) binding sites in PARN [1].
  • Finally, we present compelling evidence that the major deadenylase in C6/36 extracts is likely to be a homolog of the human poly(A) specific ribonuclease, PARN [14].

Physical interactions of PARN

  • Moreover, CUG-BP interacts with PARN in extracts by coimmunoprecipitation, and this interaction can be recapitulated using recombinant proteins [15].

Regulatory relationships of PARN

  • The CBC-mediated inhibition of PARN was cap-independent, and in keeping with this, the CBP80 subunit alone inhibited PARN [16].
  • CUG-BP binds specifically to both of these RNAs and stimulates poly(A) shortening by PARN [15].

Other interactions of PARN

  • We showed that CBC, via its 80-kDa subunit (CBP80), inhibited PARN, suggesting that CBC can regulate mRNA deadenylation [16].
  • Poly(A)-specific ribonuclease (PARN) is an oligomeric, processive, and cap-interacting 3' exonuclease [13].
  • Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability [10].

Analytical, diagnostic and therapeutic context of PARN

  • Here, we show by site-directed mutagenesis that these residues of human PARN, i.e. Asp(28), Glu(30), Asp(292), and Asp(382), are essential for catalysis but are not required for stabilization of the PARN x RNA substrate complex [1].
  • The DAN-based method examined NO-treated tumor-derived cell lysates that were immunoprecipitated with an anti-YY1 specific antibody and the NO released was determined quantitatively by fluorometry [17].
  • PATIENTS AND METHODS: BSBF at four recording sites with predominantly nutritive capillary circulation (right and left caput ulnae, right and left medial malleolus) was measured by laser Doppler flowmetry in 25 diabetic patients without cardiovascular autonomic neuropathy (D), 18 neuropathic diabetic patients (DAN) and 36 healthy controls (C) [18].


  1. Identification of the active site of poly(A)-specific ribonuclease by site-directed mutagenesis and Fe(2+)-mediated cleavage. Ren, Y.G., Martínez, J., Virtanen, A. J. Biol. Chem. (2002) [Pubmed]
  2. 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. Buiting, K., Körner, C., Ulrich, B., Wahle, E., Horsthemke, B. Cytogenet. Cell Genet. (1999) [Pubmed]
  3. Interactions between human tumor cells and fibroblasts stimulate hyaluronate synthesis. Knudson, W., Biswas, C., Toole, B.P. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  4. Ectopic expression of DAN enhances the retinoic acid-induced neuronal differentiation in human neuroblastoma cell lines. Nakamura, Y., Ozaki, T., Ichimiya, S., Nakagawara, A., Sakiyama, S. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  5. A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Gherzi, R., Lee, K.Y., Briata, P., Wegmüller, D., Moroni, C., Karin, M., Chen, C.Y. Mol. Cell (2004) [Pubmed]
  6. Interaction between a poly(A)-specific ribonuclease and the 5' cap influences mRNA deadenylation rates in vitro. Gao, M., Fritz, D.T., Ford, L.P., Wilusz, J. Mol. Cell (2000) [Pubmed]
  7. Structural insight into poly(A) binding and catalytic mechanism of human PARN. Wu, M., Reuter, M., Lilie, H., Liu, Y., Wahle, E., Song, H. EMBO J. (2005) [Pubmed]
  8. Cap-dependent deadenylation of mRNA. Dehlin, E., Wormington, M., Körner, C.G., Wahle, E. EMBO J. (2000) [Pubmed]
  9. Coordination of divalent metal ions in the active site of poly(A)-specific ribonuclease. Ren, Y.G., Kirsebom, L.A., Virtanen, A. J. Biol. Chem. (2004) [Pubmed]
  10. Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability. Seal, R., Temperley, R., Wilusz, J., Lightowlers, R.N., Chrzanowska-Lightowlers, Z.M. Nucleic Acids Res. (2005) [Pubmed]
  11. The deadenylating nuclease (DAN) is involved in poly(A) tail removal during the meiotic maturation of Xenopus oocytes. Körner, C.G., Wormington, M., Muckenthaler, M., Schneider, S., Dehlin, E., Wahle, E. EMBO J. (1998) [Pubmed]
  12. Analysis of the function of viral protein X (VPX) of HIV-2. Hu, W., Vander Heyden, N., Ratner, L. Virology (1989) [Pubmed]
  13. The mRNA cap structure stimulates rate of poly(A) removal and amplifies processivity of degradation. Martînez, J., Ren, Y.G., Nilsson, P., Ehrenberg, M., Virtanen, A. J. Biol. Chem. (2001) [Pubmed]
  14. A cell-free mRNA stability assay reveals conservation of the enzymes and mechanisms of mRNA decay between mosquito and mammalian cell lines. Opyrchal, M., Anderson, J.R., Sokoloski, K.J., Wilusz, C.J., Wilusz, J. Insect Biochem. Mol. Biol. (2005) [Pubmed]
  15. CUG-BP binds to RNA substrates and recruits PARN deadenylase. Moraes, K.C., Wilusz, C.J., Wilusz, J. RNA (2006) [Pubmed]
  16. Inhibition of mRNA deadenylation by the nuclear cap binding complex (CBC). Balatsos, N.A., Nilsson, P., Mazza, C., Cusack, S., Virtanen, A. J. Biol. Chem. (2006) [Pubmed]
  17. Inhibition of the transcription factor Yin Yang 1 activity by S-nitrosation. Hongo, F., Garban, H., Huerta-Yepez, S., Vega, M., Jazirehi, A.R., Mizutani, Y., Miki, T., Bonavida, B. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  18. Skin blood flow in the upper and lower extremities of diabetic patients with and without autonomic neuropathy. Urbancic-Rovan, V., Stefanovska, A., Bernjak, A., Azman-Juvan, K., Kocijancic, A. J. Vasc. Res. (2004) [Pubmed]
WikiGenes - Universities