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An RNA folding motif: GNRA tetraloop–receptor interactions

Published online by Cambridge University Press:  05 August 2013

Julie L. Fiore
Affiliation:
JILA, National Institute of Standards and Technology, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
David J. Nesbitt*
Affiliation:
JILA, National Institute of Standards and Technology, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
*
*Author for Correspondence: D. J. Nesbitt, JILA, National Institute of Standards and Technology, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA. Tel.: (303)492-8857; Fax: (303)492-5235; E-mail: djn@jila.colorado.edu

Abstract

Nearly two decades after Westhof and Michel first proposed that RNA tetraloops may interact with distal helices, tetraloop–receptor interactions have been recognized as ubiquitous elements of RNA tertiary structure. The unique architecture of GNRA tetraloops (N=any nucleotide, R=purine) enables interaction with a variety of receptors, e.g., helical minor grooves and asymmetric internal loops. The most common example of the latter is the GAAA tetraloop–11 nt tetraloop receptor motif. Biophysical characterization of this motif provided evidence for the modularity of RNA structure, with applications spanning improved crystallization methods to RNA tectonics. In this review, we identify and compare types of GNRA tetraloop–receptor interactions. Then we explore the abundance of structural, kinetic, and thermodynamic information on the frequently occurring and most widely studied GAAA tetraloop–11 nt receptor motif. Studies of this interaction have revealed powerful paradigms for structural assembly of RNA, as well as providing new insights into the roles of cations, transition states and protein chaperones in RNA folding pathways. However, further research will clearly be necessary to characterize other tetraloop–receptor and long-range tertiary binding interactions in detail – an important milestone in the quantitative prediction of free energy landscapes for RNA folding.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2013 

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