title: Anti-prion activity of an RNA aptamer and its structural basis.
abstract: Prion proteins (PrPs) cause prion diseases, such as bovine spongiform encephalopathy. The conversion of a normal cellular form (PrP(C)) of PrP into an abnormal form (PrP(Sc)) is thought to be associated with the pathogenesis. An RNA aptamer that tightly binds to and stabilizes PrP(C) is expected to block this conversion and to thereby prevent prion diseases. Here, we show that an RNA aptamer comprising only 12 residues, r(GGAGGAGGAGGA) (R12), reduces the PrP(Sc) level in mouse neuronal cells persistently infected with the transmissible spongiform encephalopathy agent. Nuclear magnetic resonance analysis revealed that R12, folded into a unique quadruplex structure, forms a dimer and that each monomer simultaneously binds to two portions of the N-terminal half of PrP(C), resulting in tight binding. Electrostatic and stacking interactions contribute to the affinity of each portion. Our results demonstrate the therapeutic potential of an RNA aptamer as to prion diseases.
authors.affiliation: Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Mashima
authors.forename: Fumiko
authors.initials: F
authors.lastname: Nishikawa
authors.forename: Yuji O
authors.initials: YO
authors.lastname: Kamatari
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kodaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kuwata
authors.forename: Masato
authors.initials: M
authors.lastname: Katahira
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D018621:PrPC Proteins / Q000737:chemistry*; D018620:PrPSc Proteins / Q000032:analysis
chemical_list: D052157:Aptamers, Nucleotide; D010455:Peptides; D018621:PrPC Proteins; D018620:PrPSc Proteins; C579435:R12 RNA aptamer