RNA: Structure, Biophysics and Physiology

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

In the past year, we reported the co-crystal and cryoEM structures of an in-vitro evolved DNA aptamer called Lettuce that turns on the fluorescence of conditional fluorophores. While this is an artificially evolved system, the structure of this 50 nt DNA revealed a degree of sophistication that rivals or exceeds that of many RNAs of comparable size. This allows, for the first time, a comparison of molecular architectural strategies available to folded (e.g., not simple helical) DNA and RNA, and thereby the elucidation of the structural principles that give rise to the complex architectures of natural RNA molecules. The structure of Lettuce reveled that, unlike in the case of RNA, backbone-base interactions are rare, underlining the critical role of the ribose 2'-OH in forming long-range interactions in RNA. Surprisingly, analysis of the overall strcture of Lettuce reveals that it achieves a level of compactness (defined as the number of square angstroms of solvent-accessible surface of the molecule per unit of molecular mass) comparable or exceeding that of many RNAs. Thus, DNA, which primarily employs sophisticated nucleobase-nucleobase interactions as its primary folding strategy, can form a structure with a large solvent-inaccessible interior. Moreover, analysis of the stereochemical properties of Lettuce shows that its deoxyriboses are primarily in the DNA-typical C2'-endo conformation. The structure of Lettuce shows how a DNA can attain a complex architecture employing structural strategies distinct from those of RNA, and suggests that new principles of nucleic acid structure may be forthcoming from the analysis of functional DNA molecules.