Myotonic Dystrophy: The Structure of CUG Repeats in Solution

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Title: Myotonic Dystrophy: The Structure of CUG Repeats in Solution
Author: Truong, Brian
Abstract: Myotonic dystrophy (DM), a genetic and neuromuscular disorder, is the most common form of adult-onset muscular dystrophy resulting in symptoms such as proximal muscle weakness, myotonia, iridescent cataracts and cardiac arrhythmia. Myotonic dystrophy type 1 (DM1), the most prevalent type of DM, is caused by a (CTG)n expansion in the 3â untranslated region of the dystrophin myotonin protein kinase gene. At the RNA level, the CUG repeats form a stem-loop that is thought to be the pathogenic element. Previous work in the Berglund Lab determined the crystal structure of CUG repeats and found these repeats form a structure similar to standard double-stranded A-form nucleic acid. However, since crystal structures may be misleading, we verify A-form conformation using a solution-based assay. A-form double-stranded RNA (dsRNA) is known to be cleaved into small RNA molecules in cells; therefore, the cellular machinery that recognizes and cleaves these dsRNA should degrade expanded CUG repeats. To test this hypothesis, we use an enzyme called Dicer that recognizes and cleaves A-form dsRNA. The cleavage of r(CUG)54 by Dicer confirms CUG repeats adopt a conformation similar to A-form in solution. The structure of CUG repeats may therefore lead to the design of potential drugs for DM.
Description: 29 p. A THESIS Presented to the Department of Chemistry and the Clark Honors College of the University of Oregon in partial fulfillment of the requirements for degree of Bachelor of Arts, March 2007. A print copy of this title is available through the UO Libraries under the call number: SCA Archiv Truong 2007
Date: 2007-03

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