1887

Abstract

The diversity and possible contribution of non-coding regions of the prion protein (PrP) gene () to transmissible spongiform encephalopathy susceptibility and PrP regulation are not fully known. This study defined ten ovine promoters and five untranslated region (UTR) haplotypes found in atypical and classical scrapie cases and healthy control sheep. A greater diversity of promoter and UTR haplotypes was observed in conjunction with the ARQ PrP allele (seven promoter and four UTR haplotypes), while it was observed that the other alleles were linked with a limited number of haplotypes, such as ARR, found to be linked to only two promoter and one UTR haplotypes. analysis identified potential transcription factor binding sites that differed in the promoter haplotype variants. Furthermore, a 5′ UTR internal ribosome entry site motif was identified in exon 2 and highlights a possible role for this exon in regulating PrP expression at the translational level.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.007997-0
2009-05-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/5/1289.html?itemId=/content/journal/jgv/10.1099/vir.0.007997-0&mimeType=html&fmt=ahah

References

  1. Baybutt H., Manson J. 1997; Characterisation of two promoters for prion protein (PrP) gene expression in neuronal cells. Gene 184:125–131 [CrossRef]
    [Google Scholar]
  2. Benestad S. L., Sarradin P., Thu B., Schonheit J., Tranulis M. A., Bratberg B. 2003; Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec 153:202–208 [CrossRef]
    [Google Scholar]
  3. Dawson M., Moore R. C., Bishop S. C. 2008; Progress and limits of PrP gene selection policy. Vet Res 39:
    [Google Scholar]
  4. Funke-Kaiser H., Theis S., Behrouzi T., Thomas A., Scheuch K., Zollmann F. S., Paterka M., Paul M., Orzechowski H. D. 2001; Functional characterization of the human prion protein promoter in neuronal and endothelial cells. J Mol Med 79:529–535 [CrossRef]
    [Google Scholar]
  5. Goldmann W., Hunter N., Smith G., Foster J., Hope J. 1994; PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 75:989–995 [CrossRef]
    [Google Scholar]
  6. Goldmann W., O'Neill G., Cheung F., Charleson F., Ford P., Hunter N. 1999; PrP (prion) gene expression in sheep may be modulated by alternative polyadenylation of its messenger RNA. J Gen Virol 80:2275–2283
    [Google Scholar]
  7. Green B. T., Heaton M. P., Clawson M. L., Laegreid W. W. 2006; Linkage disequilibrium across six prion gene regions spanning 20 kbp in U.S. sheep. Mamm Genome 17:1121–1129 [CrossRef]
    [Google Scholar]
  8. Hills D., Comincini S., Schlaepfer J., Dolf G., Ferretti L., Williams J. L. 2001; Complete genomic sequence of the bovine prion gene ( PRNP ) and polymorphism in its promoter region. Anim Genet 32:231–232 [CrossRef]
    [Google Scholar]
  9. Inoue S., Tanaka M., Horiuchi M., Ishiguro N., Shinagawa M. 1997; Characterization of the bovine prion protein gene: the expression requires interaction between the promoter and intron. J Vet Med Sci 59:175–183 [CrossRef]
    [Google Scholar]
  10. Jang S. K., Pestova T. V., Hellen C. U., Witherell G. W., Wimmer E. 1990; Cap-independent translation of picornavirus RNAs: structure and function of the internal ribosomal entry site. Enzyme 44:292–309
    [Google Scholar]
  11. Jean J.-C., Rich C. B., Joyce-Brady M. 2006; Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 291:L950–L956 [CrossRef]
    [Google Scholar]
  12. Komar A. A., Hatzoglou M. 2005; Internal ribosome entry sites in cellular mRNAs: mystery of their existence. J Biol Chem 280:23425–23428 [CrossRef]
    [Google Scholar]
  13. Komar A. A., Lesnik T., Cullin C., Merrick W. C., Trachsel H., Altmann M. 2003; Internal initiation drives the synthesis of Ure2 protein lacking the prion domain and affects [URE3] propagation in yeast cells. EMBO J 22:1199–1209 [CrossRef]
    [Google Scholar]
  14. Lai E. C. 2002; Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet 30:363–364 [CrossRef]
    [Google Scholar]
  15. Lee I. Y., Westaway D., Smit A. F., Wang K., Seto J., Chen L., Acharya C., Ankener M., Baskin D. other authors 1998; Complete genomic sequence and analysis of the prion protein gene region from three mammalian species. Genome Res 8:1022–1037
    [Google Scholar]
  16. Long J. S., Freese J. 2001 Regression models for categorical dependent variables using STATA College Station, TX: Stata Press;
    [Google Scholar]
  17. Matys V., Fricke E., Geffers R., Gössling E., Haubrock M., Hehl R., Hornischer K., Karas D., Kel A. E. other authors 2003; TRANSFAC: transcriptional regulation, from patterns to profiles. Nucleic Acids Res 31:374–378 [CrossRef]
    [Google Scholar]
  18. McCormack J. E., Baybutt H. N., Everington D., Will R. G., Ironside J. W., Manson J. C. 2002; PRNP contains both intronic and upstream regulatory regions that may influence susceptibility to Creutzfeldt–Jakob disease. Gene 288:139–146 [CrossRef]
    [Google Scholar]
  19. Mignone F., Grillo G., Licciulli F., Iacono M., Liuni S., Kersey P. J., Duarte J., Saccone C., Pesole G. 2005; UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs. Nucleic Acids Res 33: (Database issue), D141–D146 [CrossRef]
    [Google Scholar]
  20. Moum T., Olsaker I., Hopp P., Moldal T., Valheim M., Moum T., Benestad S. L. 2005; Polymorphisms at codons 141 and 154 in the ovine prion protein gene are associated with scrapie Nor98 cases. J Gen Virol 86:231–235 [CrossRef]
    [Google Scholar]
  21. O'Neill G. T., Donnelly K., Marshall E., Cairns D., Goldmann W., Hunter N. 2003; Characterization of ovine PrP gene promoter activity in N2a neuroblastoma and ovine foetal brain cell lines. J Anim Breed Genet 120:114–123 [CrossRef]
    [Google Scholar]
  22. O'Neill G. T., Cairns D., Toovey L., Goldmann W., Hunter N. 2005; New ovine PrP gene haplotypes as a result of single nucleotide polymorphisms in the PrP gene promoter. J Anim Breed Genet 122:86–94 [CrossRef]
    [Google Scholar]
  23. Pesole G., Liuni S. 1999; Internet resources for the functional analysis of 5′ and 3′ untranslated regions of eukaryotic mRNA. Trends Genet 15:378 [CrossRef]
    [Google Scholar]
  24. Premzl M., Delbridge M., Gready J. E., Wilson P., Johnson M., Davis J., Kuczek E., Marshall Graves J. A. 2005; The prion protein gene: identifying regulatory signals using marsupial sequence. Gene 349:121–134 [CrossRef]
    [Google Scholar]
  25. Prusiner S. B. 1998; Prions. Proc Natl Acad Sci U S A 95:13363–13383 [CrossRef]
    [Google Scholar]
  26. Saeki K., Matsumoto Y., Matsumoto Y., Onodera T. 1996; Identification of a promoter region in the rat prion protein gene. Biochem Biophys Res Commun 219:47–52 [CrossRef]
    [Google Scholar]
  27. Sander P., Hamann H., Pfeiffer I., Wemheuer W., Brenig B., Groschup M. H., Ziegler U., Distl O., Leeb T. 2004; Analysis of sequence variability of the bovine prion protein gene ( PRNP ) in German cattle breeds. Neurogenetics 5:19–25 [CrossRef]
    [Google Scholar]
  28. Sander P., Hamann H., Drogemuller C., Kashkevich K., Schiebel K., Leeb T. 2005; Bovine prion protein gene ( PRNP ) promoter polymorphisms modulate PRNP expression and may be responsible for differences in bovine spongiform encephalopathy susceptibility. J Biol Chem 280:37408–37414 [CrossRef]
    [Google Scholar]
  29. Saunders G. C., Cawthraw S., Mountjoy S., Hope J., Windl O. 2006; PrP genotypes of atypical scrapie cases in Great Britain. J Gen Virol 87:3141–3149 [CrossRef]
    [Google Scholar]
  30. Zuker M. 2003; Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31:3406–3415 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.007997-0
Loading
/content/journal/jgv/10.1099/vir.0.007997-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error