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Reduction of toxic RNAs in myotonic dystrophies type 1 and type 2 by the RNA helicase p68/DDX5

Jones, Karlie, Wei, Christina, Schoser, Benedikt, Meola, Giovanni, Timchenko, Nikolai, Timchenko, Lubov
Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.26 pp. 8041-8045
RNA, RNA helicases, biopsy, introns, mutants, oligonucleotides, patients, skeletal muscle, toxicity
Significance Inherited multisystemic diseases, myotonic dystrophies type 1 (DM1) and type 2 (DM2), are caused by long CUG and CCUG RNA repeats. The mutant RNA CCUG repeats should be degraded after intron excision; however, this RNA accumulates in cells, leading to pathology. Although mutant RNAs may be degraded with synthetic oligonucleotides, the identification of a cause of the increased stability of CUG and CCUG RNAs would help to improve the efficiency of their degradation. We found that the reduction of RNA helicase p68 in skeletal muscle biopsies of DM1 and DM2 patients contributes to the delay of degradation of the mutant RNAs. Our work suggests RNA helicase p68 as a therapeutic target in DM, correction of which improves degradation of the mutant RNAs, reducing DM pathology.