Rational and combinatorial strategies for designing oligonucleotides targeted to RNA structures
Toulmé, J.J.; Le Tinévez, R.; Boiziau, C.; Dausse, E.
Nucleic Acids Symposium Series 36: 39-41
1997
ISSN/ISBN: 0261-3166 PMID: 9478200 Document Number: 482453
Many RNA structures play a key role in the regulation of gene expression. We designed synthetic oligonucleotides able to interact with folded RNA regions (see Toulmé et al., Biochimie (1996) 78, 663-673, for a review). We have demonstrated that a decanucleotide can form a triple helix with the stem of the hairpin responsible for ribosomal frame-shifting of the gag-pro message of HTLV-I, leading to the inhibition of translation. We have isolated, through an in vitro selection procedure, from a library composed of oligonucleotides with a random part of 30 nucleotides, sequences able to bind to the TAR RNA element of HIV-1 with a dissociation constant of 20-50 nM. The association between the two partners involve non-canonical interactions. This extends the range of potential targets for antisense sequences to functional RNA structures.