Thesis Defense: How Helical Junctions Determine the Folding Stability and Allowed Conformations of Structured RNAs

Title:

“How Helical Junctions Determine the Folding Stability and Allowed Conformations of Structured RNAs”

Abstract:

Structured RNAs are inherently dynamic, exploring a diverse set of conformations within the cell. Understanding the physical origins of their folding stability, motion, and interactions with other biological actors will require characterizing the conformational landscapes they explore. The simplest motifs within structured RNAs are two helices joined by non-helical junctions. To dissect the thermodynamic properties of these fundamental helix-junction-helix (HJH) motifs, we computationally probe how junction topology, electrostatics, and tertiary contact location contribute to the folding stability of a simple tethered duplex model system. We then extend this work to construct a map of the allowed conformations of the Transactivation Response Element (TAR), a HJH motif extracted from the genome of the Human Immunodeficiency Virus. This conformational map, analogous to the Ramachandran plots for proteins, can aid in the interpretation of experiments by showing how experimental data fit into the context of the allowed conformational space. Our results indicate that the simple constraints of a single- or double-stranded junction, independent of sequence, profoundly influence the preferred location and orientation of the adjoining helices, helping to determine the folding stability and specificity of the motif. These sequence-independent effects suggest that properties as simple as a junction's topology can broadly determine the conformational landscape, stabilize desired structures, and assist in discriminating against misfolded structures, providing an additional strategy for transcending the limitations imposed by the low information content of RNA primary sequence.

Date: Thursday, October 29th, 2009 - 2pm
Location: Clark Center, S360

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