Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing
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Cell Nucleus / metabolism*
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Humans
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Middle Aged
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Muscle Proteins / genetics
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Myocytes, Cardiac / metabolism*
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Myotonic Dystrophy / genetics*
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Myotonin-Protein Kinase
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NAV1.5 Voltage-Gated Sodium Channel
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Protein Serine-Threonine Kinases / genetics
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RNA, Nuclear / metabolism*
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RNA-Binding Proteins / analysis
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RNA-Binding Proteins / metabolism*
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Sodium Channels / genetics
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Trinucleotide Repeat Expansion*
Substances
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DMPK protein, human
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MBNL1 protein, human
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MBNL2 protein, human
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Muscle Proteins
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NAV1.5 Voltage-Gated Sodium Channel
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RNA, Nuclear
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RNA-Binding Proteins
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SCN5A protein, human
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Sodium Channels
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Myotonin-Protein Kinase
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Protein Serine-Threonine Kinases