RNA and Protein function in Telomerase

Harvard University, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): Telomerase is a specialized reverse transcriptase responsible for synthesizing telomeric DNA at the ends of linear chromosomes, thereby promoting genomic stability. The enzymatic activity of the telomerase ribonucleoprotein (RNP) requires both the telomerase RNA and the telomerase reverse transcriptase. The proposed research employs single molecule fluorescence resonance energy transfer (FRET) and force spectroscopy to test the hypothesis that dynamic changes in RNA structure are a central feature of the telomerase catalytic cycle and RNP maturation pathway. Single molecule FRET is a proven method for studying structural dynamics and determining non-accumulating folding intermediates of RNA molecules, while force spectroscopic techniques have provided insight into the mechanochemistry of a host of cellular motor proteins. The application of biophysical techniques to studies of the telomerase ribonucleoprotein (RNP) will establish a paradigm for future research on RNP enzymes, with particular emphasis on relating enzymatic function with human disease.