ArticlePloS one2019
(CTG)n repeat-mediated dysregulation of MBNL1 and MBNL2 expression during myogenesis in DM1 occurs already at the myoblast stage.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Unleashing the power of DNA-encoded libraries for challenging targets in drug discovery.Pharmaceutical science advances · 2026Review
- MBNL depletion drives stem cell fusion and immature myonuclear states in myotonic dystrophy type 1.Nature communications · 2026Article
- Commitment to Myogenic Differentiation Significantly Aggravates the RNA Phenotype in Myotonic Dystrophy Type 1.Neuropathology and applied neurobiology · 2026Article
- Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1.American journal of human genetics · 2026Article
- MBNL loss of function in smooth muscle as a model for myotonic dystrophy associated gastrointestinal dysmotility.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Repeat Expansions with Small TTTCA Insertions in MARCHF6 Cause Familial Myoclonus without Epilepsy.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Characterization ofNAR molecular medicine · 2025Article
- AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.Science advances · 2024Article
- Ameliorated cellular hallmarks of myotonic dystrophy in hybrid myotubes from patient and unaffected donor cells.Stem cell research & therapy · 2024Article
- Two Decades of Arrayed Imaging Reflectometry for Sensitive, High-Throughput Biosensing.Biosensors · 2023Review
- Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development.Human molecular genetics · 2023Article
- Study of an RNA-Focused DNA-Encoded Library Informs Design of a Degrader of a r(CUG) Repeat Expansion.Journal of the American Chemical Society · 2022Article
- Clinical and Molecular Insights into Gastrointestinal Dysfunction in Myotonic Dystrophy Types 1 & 2.International journal of molecular sciences · 2022Review
- Design of novel small molecule base-pair recognizers of toxic CUG RNA transcripts characteristics of DM1.Computational and structural biotechnology journal · 2021Article
- RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease.Frontiers in cell and developmental biology · 2021Review
- Application of CRISPR-Cas9-Mediated Genome Editing for the Treatment of Myotonic Dystrophy Type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Recovery in the Myogenic Program of Congenital Myotonic Dystrophy Myoblasts after Excision of the Expanded (CTG)International journal of molecular sciences · 2019Article
- MicroRNA-Based Therapeutic Perspectives in Myotonic Dystrophy.International journal of molecular sciences · 2019Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myotonic dystrophy type 1 (DM1) is a severe neuromuscular disorder caused by the expression of trinucleotide repeat-containing DMPK transcripts. Abnormally expanded (CUG)n repeats in these transcripts form hairpin-like structures that cause the RNA to accumulate in the cell nucleus by sequestering isoforms of the Muscleblind (MBNL) family, tissue-specific regulators of developmentally programmed, post-transcriptional processes in RNA metabolism. Through this mechanism, the function of MBNL in RNA processing becomes dominantly perturbed, which eventually leads to aberrant alternative splicing and the expression of foetal splice variants of a wide variety of proteins, including the MBNL isoforms themselves. Here, we employ a patient-derived muscle cell model for DM1 to examine in detail the expression of MBNL RNA and protein variants during myogenic differentiation. This DM1 model consists of a panel of isogenic myoblast cell lines that either contain a pathogenic DMPK allele with a congenital mutation of 2600 triplets, or lack this expanded repeat through CRISPR/Cas9-mediated gene editing. We found that the temporal expression levels of MBNL1, MBNL2 and MBNL3 RNAs are not influenced by presence of the (CTG)2600 repeat during myogenesis in vitro. However, throughout myoblast proliferation and differentiation to myotubes a disproportionate inclusion of MBNL1 exon 5 and MBNL2 exons 5 and 8 occurs in cells with the (CTG)2600 repeat. As a consequence, a reduced quantity and imbalanced collection of splice variants of MBNL1 and MBNL2 accumulates in both the cytoplasm and the nucleus of DM1 myoblasts and myotubes. We thus propose that both the quantitative and qualitative changes in the intracellular partitioning of MBNL proteins are a pivotal cause of skeletal muscle problems in DM1, starting already in muscle progenitor cells.
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