1. Department of Biochemistry, 7200 Vail Building, Dartmouth Medical School, Hanover, New Hampshire 03755, USA

Correspondence to: Surachai Supattapone¹ Email: supattapone@dartmouth.edu

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, PrP^Sc, seems to be generated by template-induced conformational change of a normally expressed glycoprotein, PrP^C (ref. 2). Although numerous studies have established the conversion of PrP^C to PrP^Sc as the central pathogenic event of prion disease, it is unknown whether cellular factors other than PrP^C might be required to stimulate efficient PrP^Sc production. We investigated the biochemical amplification of protease-resistant PrP^Sc-like protein (PrPres) using a modified version³ of the protein-misfolding cyclic amplification method⁴. Here we report that stoichiometric transformation of PrP^C 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.