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Nucleic Acids Research Advance Access published online on May 30, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm374
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Cellular antisense activity of peptide nucleic acid (PNAs) targeted to HIV-1 polypurine tract (PPT) containing RNA

Fatima Boutimah-Hamoudi1,2,3, Erwan Leforestier1,2,3, Catherine Sénamaud-Beaufort1,2,3, Peter E. Nielsen4, Carine Giovannangeli1,2,3 and Tula Ester Saison-Behmoaras1,2,3,*

1INSERM, U565, Acides nucléiques: dynamique, ciblage et fonctions biologiques, 57 rue Cuvier, CP26, Paris Cedex 05, F-75231, France, 2MNHN, USM503, Département de « Régulations, développement et diversité moléculaire », Laboratoire des Régulations et dynamique des génomes, 57 rue Cuvier, CP26, Paris Cedex 5, F-75231, France, 3CNRS, UMR5153, Acides nucléiques: dynamique, ciblage et fonctions biologiques, 57 rue Cuvier, CP26, Paris Cedex 5, F-75231, France and 4Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, The Panum Institute, Blegdamsvej 3c, DK-2200 Copenhagen N, Denmark

*To whom correspondence should be addressed. Tel: +33 1 40 79 36 86; Fax: +33 1 40 79 37 05; Email: tula{at}mnhn.fr

Received April 3, 2007. Revised April 26, 2007. Accepted April 27, 2007.

DNA and RNA oligomers that contain stretches of guanines can associate to form stable secondary structures including G-quadruplexes. Our study shows that the (UUAAAAGAAAAGGGGGGAU) RNA sequence, from the human immunodeficiency virus type 1 (HIV-1 polypurine tract or PPT sequence) forms in vitro a stable folded structure involving the G-run. We have investigated the ability of pyrimidine peptide nucleic acid (PNA) oligomers targeted to the PPT sequence to invade the folded RNA and exhibit biological activity at the translation level in vitro and in cells. We find that PNAs can form stable complexes even with the structured PPT RNA target at neutral pH. We show that T-rich PNAs, namely the tridecamer-I PNA (C4T4CT4) forms triplex structures whereas the C-rich tridecamer-II PNA (TC6T4CT) likely forms a duplex with the target RNA. Interestingly, we find that both C-rich and T-rich PNAs arrested in vitro translation elongation specifically at the PPT target site. Finally, we show that T-rich and C-rich tridecamer PNAs that have been identified as efficient and specific blockers of translation elongation in vitro, specifically inhibit translation in streptolysin-O permeabilized cells where the PPT target sequence has been introduced upstream the reporter luciferase gene.


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