Intrinsic Contribution of the 2′-Hydroxyl to RNA Conformational Heterogeneity

Citations Over TimeTop 24% of 2012 papers

Abstract

Canonical duplex RNA assumes only the A-form conformation at the secondary structure level while, in contrast, a wide range of noncanonical, tertiary conformations of RNA occur. Here, we show how the 2'-hydroxyl controls RNA conformational properties. Quantum mechanical calculations reveal that the orientation of the 2'-hydroxyl significantly alters the intrinsic flexibility of the phosphodiester backbone, favoring the A-form in duplex RNA when it is in the base orientation and facilitating sampling of a wide range of noncanonical, tertiary structures when it is in the O3' orientation. Influencing the orientation of the 2'-hydroxyl are interactions with the environment, as evidenced by crystallographic survey data, indicating the 2'-hydroxyl to sample more of the O3' orientation in noncanonical RNA structures. These results indicate that the 2'-hydroxyl acts as a "switch", both limiting the conformation of RNA to the A-form at the secondary structure level and allowing RNA to sample a wide range of noncanonical tertiary conformations.

Related Papers

• → Nonenzymatic Recombination of RNA: Possible Mechanism for the Formation of Novel Sequences(2007)39 cited
• → Replacement of the phosphodiester linkage in oligonucleotides by heterocycles: the effect of triazole- and imidazole-modified backbones on DNA/RNA duplex stability(1997)24 cited
• → Thermal melting studies with PNA and PNA-DNA chimera(1999)5 cited
• → Occurrence of 2'-5' phosphodiester linkages in RNA preparations. III. Formation of 2'-5' phosphodiester linkages in polyribonucleotides.(1977)
• → Formation of 2′-5′ Phosphodiester Linkages in Polyribonucleotides(1977)