[Frontiers in Bioscience 15, 550-563, January 1, 2010]

Aptamers to explore prion protein interactions with nucleic acids

Daniel Marc1

1INRA, UR1282, Infectiologie Animale et Sante Publique, IASP, Nouzilly,F-37380, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The SELEX method
4. Properties of aptamers and other nucleic acid ligands of PrP
4.1. General properties
4.2. Sequence features
4.3. Structural features in PrP-specific aptamers.
5. Binding properties, and specificity of prion-nucleic acid interactions
6. Mapping the aptamer-binding site on PrP
6.1. The N-terminal lysine cluster
6.2. The second lysine cluster and the 90-130 region of PrP
6.3. The structured domain of PrP
7. Biological relevance of the PrP-nucleic-acid interaction
7.1. Aptamers as clues to functional ligands of PrP in vivo
7.2. Alternative methods to isolate functional nucleic acid ligands of PrP
7.3. Uncovering possible functions of PrP
8. Aptamers as tools
8.1. Detection of PrPSc
8.2. Removal and concentration of PrPSc
8.3. Preventing PrP misfolding: therapy perspectives
9. Summary and perspectives
10. Acknowledgements
11. References

1. ABSTRACT

A misfolded isoform of the prion protein (PrP) is the essential component of the prion diseases' agent. The prion concept has progressively gained acceptance, in a large part thanks to the realization that it played a role not only in the transmissible spongiform encephalopathies, but also in the non-Mendelian propagation of self-perpetuating phenotypes of the yeast Saccharomyces cerevisiae. Uncertainties about the nature of the agent and the function of PrP have fostered searches of nucleic acid ligands of the protein. In vitro methods of nucleic acid evolutions have been used to identify RNAs or DNAs that bind PrP, towards the triple objective of i) setting up new diagnostic tools, ii) identifying nucleic acids with which PrP may interact, as part of its physiological or pathological function, and iii) elucidating the pathological transconformation of PrP. This review will focus on these studies, their methods, the knowledge acquired from them about the prion protein, and the possibilities that they offer in the areas of diagnosis and therapy of prion diseases.