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(Circulation Research. 2005;97:1152.)
© 2005 American Heart Association, Inc.

Cellular Biology

Nuclear RNA Foci in the Heart in Myotonic Dystrophy

Ami Mankodi, Xiaoyan Lin, Burns C. Blaxall, Maurice S. Swanson, Charles A. Thornton

From the Departments of Neurology (A.M., C.A.T.), Neuroscience (X.L.), and Cardiovascular Research Institute (B.C.B.), University of Rochester Medical Center, New York; and the Department of Molecular Genetics and Microbiology (M.S.S.), University of Florida, Gainesville.

Correspondence to Charles A. Thornton, MD, Department of Neurology, Box 673, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642. E-mail Charles_Thornton{at}URMC.Rochester.Edu

The disease mechanism underlying myotonic dystrophy type 1 (DM1) pathogenesis in skeletal muscle may involve sequestration of RNA binding proteins in nuclear foci of expanded poly(CUG) RNA. Here we report evidence for a parallel mechanism in the heart. Accumulation of expanded poly(CUG) RNA in nuclear foci is associated with sequestration of muscleblind proteins and abnormal regulation of alternative splicing in DM1 cardiac muscle. A toxic effect of RNA with an expanded repeat may contribute to cardiac disease in DM1.

Key Words: myotonic dystrophy • CUG repeats • RNA foci • muscleblind • alternative splicing

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