Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 26, Pages 8041-8045Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1422273112
Keywords
myotonic dystrophy; RNA foci; p68 RNA helicase; CUG repeats
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Funding
- National Institutes of Health [AR044387, AR052791, AR064488, CA159942, DK102597, GM551888]
- Fondazione Malattie Miotoniche
- Cincinnati Children's Hospital Medical Center
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Myotonic dystrophies type 1 (DM1) and type 2 (DM2) are neuromuscular diseases, caused by accumulation of CUG and CCUG RNAs in toxic aggregates. Here we report that the increased stability of the mutant RNAs in both types of DMis caused by deficiency of RNA helicase p68. We have identified p68 by studying CCUG-binding proteins associated with degradation of the mutant CCUG repeats. Protein levels of p68 are reduced in DM1 and DM2 biopsied skeletal muscle. Delivery of p68 in DM1/2 cells causes degradation of the mutant RNAs, whereas delivery of p68 in skeletal muscle of DM1 mouse model reduces skeletal muscle myopathy and atrophy. Our study shows that correction of p68 may reduce toxicity of the mutant RNAs in DM1 and in DM2.
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