Nuclear RNA foci in the heart in myotonic dystrophy.
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.
Mankodi
Ami
A
Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Lin
Xiaoyan
X
Blaxall
Burns C
BC
Swanson
Maurice S
MS
Thornton
Charles A
CA
D017398:Alternative Splicing; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D062554:NAV1.5 Voltage-Gated Sodium Channel; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015138:RNA, Nuclear / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics; D019680:Trinucleotide Repeat Expansion
C585517:DMPK protein, human; C493663:MBNL1 protein, human; C499444:MBNL2 protein, human; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015138:RNA, Nuclear; D016601:RNA-Binding Proteins; C568320:SCN5A protein, human; D015222:Sodium Channels; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases