Kinetic Modeling of RNA Folding and Allostery

The three dimensional arrangement of nucleotides in RNA molecules are indispensable for their biological function. However, the rules and relationships that define how RNA “folds” into these biologically relevant conformations, or states, is poorly understood. In order to examine how cations and proteins can influence this process, I focused on measuring the folding process of a 60mer fragment of the GTPase center of the large subunit of the ribosome. The folding pathway was interrogated with a wide spectrum of biophysical techniques. We elucidated a six state divalent ion induced folding pathway and an allosteric mechanism underlying the binding of the L11 protein. This work establishes the remarkable complexity of RNA folding and binding of this particular molecule, and suggests that multi-state folding pathways might not be the exception, but the rule