Absence of Hydrogen Bonding in Adjacent UU  and AG Mismatches in an Isolated Internal Loop from Ribosomal RNA

Group Objective

The research in Professor Turner's group focuses on the forces directing nucleic acid chemistry, with particular emphasis on RNA folding. This chemistry is important for the biochemical basis of life and for design of therapeutics. Nevertheless, much of it is not well understood. Studies of the properties of short oligonucleotides provide insight into the relative contributions of solvent, electronic interactions, and hydrogen bonding in determining the structure, thermodynamics, and dynamics of nucleic acids. This information is incorporated into computer programs to predict the secondary and three-dimensional structure of an RNA. The results from these studies are providing the foundation for a bioinformatics approach to develop deeper interpretations of the many nucleic acid sequences being determined by the Human Genome Project and other sequencing efforts.

To test the effectiveness of predictions, thestructure and dynamics of self-splicing intervening sequences from the ribosomal RNA precursors of Tetrahymena thermophila and Pneumocystis carinii are also being studied. This work provides insight into the role of tertiary interactions in determining RNA folding. It has also inspired the concept that binding enhanced by tertiary interaction (BETI) can be used as a design principle in developing antisense therapeutics that target RNA. The group is interested in applying structure prediction and antisense design principles to improve targeting of group I introns and other RNAs

The solutions to these challenging problems require many different clues. The group therefore applies the methods of UV, CD, and NMR spectroscopies, thermodynamics, oligonucleotide synthesis, chemical mapping of RNA structure, and rapid reaction kinetics. By combining the results obtained from these various techniques, it is often possible to deduce unifying concepts for the nucleic acid chemistry.

 

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