Published online before print October 27, 2005, doi: 10.1161/01.RES.0000193598.89753.e3
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Submitted on June 14, 2005
Revised on September 15, 2005
Accepted on October 18, 2005
Nuclear RNA Foci in the Heart in Myotonic Dystrophy
Ami Mankodi ;
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.
* To whom correspondence should be addressed. 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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