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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Mashima T,Nishikawa F,Kamatari YO,Fujiwara H,Saimura M,Nagata T,Kodaki T,Nishikawa S,Kuwata K,Katahira Mdoi
10.1093/nar/gks1132subject
Has Abstractpub_date
2013-01-01 00:00:00pages
1355-62issue
2eissn
0305-1048issn
1362-4962pii
gks1132journal_volume
41pub_type
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