Interaction of DNA Intramolecular Structures with Their Complementary Strands: A Thermodynamic Approach for the Control of Gene Expression
The folding of mRNA sequences into secondary/tertiary structures plays an important role in RNA and DNA function and expression. Disruption of these structures can potentially be used in the control of gene expression. However, a detailed understanding of the physicochemical properties of nucleic acid structures is needed before this targeting approach can be used. In this chapter, we have examined six intramolecular DNA structures and have investigated their reaction thermodynamics with single strands partially complementary to their stems and loops. We measured the heat of each reaction directly using isothermal titration calorimetry. These are compared with the heat measured indirectly using Hess cycles obtained from differential scanning calorimetric unfolding thermodynamic profiles. Each reaction yielded favorable free energy terms that were enthalpy driven, indicating each complementary strand was able to disrupt the intramolecular complex. In short, we have developed a thermodynamic approach that can be used in the control of gene expression that targets the loops of secondary structures formed by mRNA.
KeywordsTargeting DNA secondary structures Antisense Heat Thermodynamics
This work was supported by Grant MCB-1122029 from the National Science Foundation and a GAANN graduate fellowship (C.R.) of Grant P200A120231 from the US Department of Education.