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Brian Truong
Biochemistry/Honors College

Andy Berglund, Mentor
Jill Murray, Mentor

Myotonic Dystrophy: The Structure of CUG Repeats in Solution

Myotonic dystrophy (DM), a genetic and neuromuscular disorder, is a common form of adult-onset muscular dystrophy that results 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 3' 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. We determined the crystal structure of CUG repeats and found these repeats form a structure similar to standard double-stranded A-form nucleic acid. A-form, double-stranded RNA (dsRNA) is known to be cleaved into small RNA molecules in cells. Therefore, we predict that the cellular machinery that recognizes and cleaves these dsRNA should degrade expanded CUG repeats. To test this hypothesis, we will monitor the cleavage of CUG repeats in solution using an enzyme that recognizes and cleaves A-form dsRNA.