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Science 14 August 1992:
Vol. 257. no. 5072, pp. 958 - 961
DOI: 10.1126/science.1502560

Articles

Science, Vol 257, Issue 5072, 958-961
Copyright © 1992 by American Association for the Advancement of Science


articles

Pseudo--half-knot formation with RNA

DJ Ecker, TA Vickers, TW Bruice, SM Freier, RD Jenison, M Manoharan, and M Zounes

ISIS Pharmaceuticals, Carlsbad, CA 92008.

A pseudo--half-knot can be formed by binding an oligonucleotide asymmetrically to an RNA hairpin loop. This binding motif was used to target the human immunodeficiency virus TAR element, an important viral RNA structure that is the receptor for Tat, the major viral transactivator protein. Oligonucleotides complementary to different halves of the TAR structure bound with greater affinity than molecules designed to bind symmetrically around the hairpin. The pseudo--half-knot--forming oligonucleotides altered the TAR structure so that specific recognition and binding of a Tat-derived peptide was disrupted. This general binding motif may be used to disrupt the structure of regulatory RNA hairpins.


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PD-loop: A complex of duplex DNA with an oligonucleotide.
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The Influence of Antisense Oligonucleotide-induced RNA Structure on Escherichia coli RNase H1 Activity.
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Combinatorial Screening and Rational Optimization for Hybridization to Folded Hepatitis C Virus RNA of Oligonucleotides with Biological Antisense Activity.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)