Repression of nuclear CELF activity can rescue CELF-regulated alternative splicing defects in skeletal muscle models of myotonic dystrophy | Zendy

Dara S. Berger | Zendy; Andrea N. Ladd | Zendy

Open Access

Repression of nuclear CELF activity can rescue CELF-regulated alternative splicing defects in skeletal muscle models of myotonic dystrophy

Author(s) -

Dara S. Berger,

Andrea N. Ladd

Publication year - 2012

Publication title -

plos currents

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.282

H-Index - 49

ISSN - 2157-3999

DOI - 10.1371/currents.rrn1305

Subject(s) - myotonic dystrophy , rna splicing , trinucleotide repeat expansion , alternative splicing , psychological repression , muscular dystrophy , biology , transgene , myotonia , genetically modified mouse , computational biology , bioinformatics , genetics , gene , gene expression , exon , rna , allele

Myotonic dystrophy type 1 (DM1) is caused by the expansion of CUG repeats in the 3’ UTR of DMPK transcripts. DM1 pathogenesis has been attributed in part to alternative splicing dysregulation via elevation of CUG-BP, Elav-like family member 1 (CELF1). Several therapeutic approaches have been tested in cells and mice, but no previous studies had specifically targeted CELF1. Here, we show that repressing CELF activity rescues CELF-dependent alternative splicing in cell culture and transgenic mouse models of DM1. CELF-independent splicing, however, remained dysregulated. These data highlight both the potential and limitations of targeting CELF1 for the treatment of DM1.

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