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Nucleic Acids Research Advance Access published online on December 26, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm1141
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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.

RNA

DNA mimicry by a high-affinity anti-NF-{kappa}B RNA aptamer

Nicholas J. Reiter1, L. James Maher, III2 and Samuel E. Butcher1,*

1Department of Biochemistry, University of Wisconsin-Madison and 2Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

*To whom correspondence should be addressed. Tel: 608-263-4081; Fax: 608-262-3453; Email: butcher{at}biochem.wisc.edu

Received September 20, 2007. Revised November 21, 2007. Accepted December 7, 2007.

The binding of RNA molecules to proteins or other ligands can require extensive RNA folding to create an induced fit. Understanding the generality of this principle involves comparing structures of RNA before and after complex formation. Here we report the NMR solution structure of a 29-nt RNA aptamer whose crystal structure had previously been determined in complex with its transcription factor target, the p502 form of NF-{kappa}B. The RNA aptamer internal loop structure has pre-organized features that are also found in the complex, including non-canonical base pairing and cross-strand base stacking. Remarkably, the free RNA aptamer structure possesses a major groove that more closely resembles B-form DNA than RNA. Upon protein binding, changes in RNA structure include the kinking of the internal loop and distortion of the terminal tetraloop. Thus, complex formation involves both pre-formed and induced fit binding interactions. The high affinity of the NF-{kappa}B transcription factor for this RNA aptamer may largely be due to the structural pre-organization of the RNA that results in its ability to mimic DNA.


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