CUG REPEATS PRESENT IN MYOTONIN KINASE RNA FORM METASTABLE SLIPPERY HAIRPINS

We show that CUG repeats form ''slippery'' hairpins in their natural s equence context of the myotonin kinase gene transcript. This novel typ e of RNA structure is characterized by strong S-1 and T-1 nuclease and lead cleavages in the terminal loop and by mild lead cleavages in the hairpin stem. The latter effect indicates a relaxed metastable struct ure of the stem. (CUG)(5) repeats do not form any detectable secondary structure, whereas hairpins of increasing stability are formed by (CU G)(11), (CUG)(21), and (CUG)(49). The potential role of the RNA hairpi n structure in the pathogenesis of myotonic dystrophy is discussed.