RNA molecules stimulate prion protein conversion (original) (raw)
- Letter
- Published: 16 October 2003
Nature volume 425, pages 717–720 (2003)Cite this article
- 2430 Accesses
- 422 Citations
- 106 Altmetric
- Metrics details
Abstract
Much evidence supports the hypothesis that the infectious agents of prion diseases are devoid of nucleic acid, and instead are composed of a specific infectious protein1. This protein, PrPSc, seems to be generated by template-induced conformational change of a normally expressed glycoprotein, PrPC (ref. 2). Although numerous studies have established the conversion of PrPC to PrPSc as the central pathogenic event of prion disease, it is unknown whether cellular factors other than PrPC might be required to stimulate efficient PrPSc production. We investigated the biochemical amplification of protease-resistant PrPSc-like protein (PrPres) using a modified version3 of the protein-misfolding cyclic amplification method4. Here we report that stoichiometric transformation of PrPC to PrPres in vitro requires specific RNA molecules. Notably, whereas mammalian RNA preparations stimulate in vitro amplification of PrPres, RNA preparations from invertebrate species do not. Our findings suggest that host-encoded stimulatory RNA molecules may have a role in the pathogenesis of prion disease. They also provide a practical approach to improve the sensitivity of diagnostic techniques based on PrPres amplification.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Similar content being viewed by others
References
- Prusiner, S. B. Novel proteinaceous infectious particles cause scrapie. Science 216, 136–144 (1982)
CAS PubMed Google Scholar - Prusiner, S. B. (ed.) Prion Biology and Diseases (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1999)
- Lucassen, R., Nishina, K. & Supattapone, S. In vitro amplification of protease-resistant prion protein requires free sulfhydryl groups. Biochemistry 42, 4127–4135 (2003)
Article CAS PubMed Google Scholar - Saborio, G. P., Permanne, B. & Soto, C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411, 810–813 (2001)
Article CAS PubMed Google Scholar - Lockard, R. E. & Kumar, A. Mapping tRNA structure in solution using double-strand-specific ribonuclease V1 from cobra venom. Nucleic Acids Res. 9, 5125–5140 (1981)
Article CAS PubMed PubMed Central Google Scholar - Banks, G. R. A ribonuclease H from Ustilago maydis. Properties, mode of action and substrate specificity of the enzyme. Eur. J. Biochem. 47, 499–507 (1974)
Article CAS PubMed Google Scholar - Kocisko, D. A. et al. Cell-free formation of protease-resistant prion protein. Nature 370, 471–474 (1994)
Article CAS PubMed Google Scholar - Caughey, B., Horiuchi, M., Demaimay, R. & Raymond, G. J. Assays of protease-resistant prion protein and its formation. Methods Enzymol. 309, 122–133 (1999)
Article CAS PubMed Google Scholar - Derrington, E. et al. PrPC has nucleic acid chaperoning properties similar to the nucleocapsid protein of HIV-1. C. R. Acad. Sci. III 325, 17–23 (2002)
CAS Google Scholar - Moscardini, M. et al. Functional interactions of nucleocapsid protein of feline immunodeficiency virus and cellular prion protein with the viral RNA. J. Mol. Biol. 318, 149–159 (2002)
Article CAS PubMed Google Scholar - Gabus, C. et al. The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1. J. Biol. Chem. 276, 19301–19309 (2001)
Article CAS PubMed Google Scholar - Gabus, C. et al. The prion protein has DNA strand transfer properties similar to retroviral nucleocapsid protein. J. Mol. Biol. 307, 1011–1021 (2001)
Article CAS PubMed Google Scholar - Nandi, P. K., Leclerc, E., Nicole, J. C. & Takahashi, M. DNA-induced partial unfolding of prion protein leads to its polymerisation to amyloid. J. Mol. Biol. 322, 153–161 (2002)
Article CAS PubMed Google Scholar - Cordeiro, Y. et al. DNA converts cellular prion protein into the β-sheet conformation and inhibits prion peptide aggregation. J. Biol. Chem. 276, 49400–49409 (2001)
Article CAS PubMed Google Scholar - Weissmann, C. A ‘unified theory’ of prion propagation. Nature 352, 679–683 (1991)
Article CAS PubMed Google Scholar - Chapon, C., Cech, T. R. & Zaug, A. J. Polyadenylation of telomerase RNA in budding yeast. RNA 3, 1337–1351 (1997)
CAS PubMed PubMed Central Google Scholar
Acknowledgements
The authors thank G. Saborio, C. Soto, V. Ambros, C. Cole and W. Wickner for helpful advice. This work was supported by the Burroughs Wellcome Fund Career Development Award, the Hitchcock Foundation, and an NIH Clinical Investigator Development Award.
Author information
Authors and Affiliations
- Department of Biochemistry, Dartmouth Medical School, 7200 Vail Building, Hanover, New Hampshire, 03755, USA
Nathan R. Deleault, Ralf W. Lucassen & Surachai Supattapone
Authors
- Nathan R. Deleault
You can also search for this author inPubMed Google Scholar - Ralf W. Lucassen
You can also search for this author inPubMed Google Scholar - Surachai Supattapone
You can also search for this author inPubMed Google Scholar
Corresponding author
Correspondence toSurachai Supattapone.
Ethics declarations
Competing interests
The authors declare that they have no competing financial interests.
Supplementary information
Rights and permissions
About this article
Cite this article
Deleault, N., Lucassen, R. & Supattapone, S. RNA molecules stimulate prion protein conversion.Nature 425, 717–720 (2003). https://doi.org/10.1038/nature01979
- Received: 04 July 2003
- Accepted: 31 July 2003
- Issue Date: 16 October 2003
- DOI: https://doi.org/10.1038/nature01979