Development of JB Recognition Codes for Manipulation of RNA Structures and Functions

Carnegie Mellon University, Pittsburgh PA

Investigators

Abstract

RNA molecules have diverse and essential functions in cells, related to their three-dimensional structures. This project is developing a more comprehensive molecular toolbox than is currently available to manipulate RNA structure in an attempt to advance the understanding of their biological roles. This research program serves as a training ground for high school, undergraduate and graduate students and postdoctoral associates. Training is provided in synthetic, physical organic, analytical, and biophysical chemistry, as well as in molecular and cellular biology. Implementation of this research project is strengthening the ongoing effort to build a Chemical Biology program, at Carnegie Mellon University. The program promotes rigorous undergraduate research training and fosters interest in science among K-12 students and teachers in the Greater Western Pennsylvania area. This interdisciplinary program is providing students and research associates with a unique skillset essential for their future career in graduate schools as well as in industry. This research project is developing an entirely new set of nucleic acid recognition codes, namely "Janus" bases (or JBs). These bases are capable of forming bifacial H-bonding interactions with adjoining nucleobases on the opposing strands of RNA double helix. In particular, the research is chemically synthesizing JBs and the corresponding millamolecular ligands and evaluating their binding properties with a fluorescence-based assay. The proposed JBs are designed to bind to all 16 possible combinations of matched and mismatched base-pairs, providing a complete toolset for manipulation of RNA structure and function. In addition to their small size and digital recognition, the other benefits of JBs include improvements in recognition specificity and selectivity. Completion of this project will allow the determination of the feasibility of JB recognition and the ability to manipulate RNA structure and function, pertinent to the development of a malleable molecular platform for binding rapidly evolving RNA targets.