NR APGV
AU Deleault,N.R.; Lucassen,R.W.; Supattapone,S.
TI RNA molecules stimulate prion protein conversion
QU Nature 2003 Oct 16; 425(6959): 717-20
KI Nature. 2003 Oct 16;425(6959):673-4. PMID: 14562085
PT journal article
AB 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 protein. 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 version of the protein-misfolding cyclic amplification method. 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.
MH Animals; Brain/metabolism; Caenorhabditis elegans/genetics; Drosophila melanogaster/genetics; Endonucleases/metabolism; Escherichia coli/genetics; Female; Hamsters; Mesocricetus/genetics; Mice; Prion Diseases/genetics/*metabolism; Prions/*chemistry/*metabolism; Protein Conformation; *Protein Folding; RNA/genetics/isolation & purification/*metabolism; Saccharomyces cerevisiae/genetics; Scrapie/genetics/metabolism; Species Specificity; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Department of Biochemistry, 7200 Vail Building, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
SP englisch
PO England