Transcriptional adaptation upregulates utrophin in Duchenne muscular dystrophy.

ABSTRACT: Duchenne muscular dystrophy (DMD) is a muscle-degenerating disease caused by mutations in the DMD gene, which encodes the dystrophin protein^1,2. Utrophin (UTRN), the genetic and functional paralogue of DMD, is upregulated in some DMD patients^3-5. To further investigate this UTRN upregulation, we first developed an inducible messenger RNA (mRNA) degradation system for DMD by introducing a premature termination codon (PTC) in one of its alternatively spliced exons. Inclusion of the PTC-containing exon triggers DMD mutant mRNA decay and UTRN upregulation. Notably, blocking nonsense-mediated mRNA decay results in the reversal of UTRN upregulation, whereas overexpressing DMD does not. Furthermore, overexpressing DMD^PTC minigenes in wild-type cells causes UTRN up

SUBMITTER: Falcucci L 

PROVIDER: S-EPMC11903304 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature