DNA mimicry by a high-affinity anti-NF-κB RNA aptamer

Nicholas J. Reiter, L James Maher III, Samuel E. Butcher

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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-κB. 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-κB 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.

Original languageEnglish (US)
Pages (from-to)1227-1236
Number of pages10
JournalNucleic Acids Research
Volume36
Issue number4
DOIs
StatePublished - Mar 2008

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Nucleotide Aptamers
Molecular Mimicry
RNA
Transcription Factors
RNA Folding
B-Form DNA
Protein Binding
Base Pairing
Ligands
DNA
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

DNA mimicry by a high-affinity anti-NF-κB RNA aptamer. / Reiter, Nicholas J.; Maher III, L James; Butcher, Samuel E.

In: Nucleic Acids Research, Vol. 36, No. 4, 03.2008, p. 1227-1236.

Research output: Contribution to journalArticle

Reiter, Nicholas J. ; Maher III, L James ; Butcher, Samuel E. / DNA mimicry by a high-affinity anti-NF-κB RNA aptamer. In: Nucleic Acids Research. 2008 ; Vol. 36, No. 4. pp. 1227-1236.
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