ArticleNature medicine2011
Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03424460 (Venous Thromboembolism in Myotonic Dystrophy Type 1), which is not on this map. Cited by 215 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Venous Thromboembolism in Myotonic Dystrophy Type 1
Who cites it
215 citing papers in PubMed, 326 citations in OpenAlex.
- CRISPR/dCas9-mediated tuning of DMPK transcription reveals a quantitative relationship between toxic repeat RNA expression and MBNL1 activity in myotonic dystrophy.Human molecular genetics · 2026Article
- MBNL depletion drives stem cell fusion and immature myonuclear states in myotonic dystrophy type 1.Nature communications · 2026Article
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- Current biomarker development in myotonic dystrophies.Journal of neurology · 2026Review
- Changes in RNA splicing as a surrogate endpoint for myotonic dystrophy Type 1 (DM1) clinical trials.Journal of neuromuscular diseases · 2026Review
- Commitment to Myogenic Differentiation Significantly Aggravates the RNA Phenotype in Myotonic Dystrophy Type 1.Neuropathology and applied neurobiology · 2026Article
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- Proteomics-based evaluation of AAV dystrophin gene therapy outcomes in mdx skeletal muscle.JCI insight · 2026Article
- Alternative Splicing of SORBS1 Affects Neuromuscular Junction Integrity in Myotonic Dystrophy Type 1.Journal of cachexia, sarcopenia and muscle · 2025Article
- Alternative splicing of the Snap23 microexon is regulated by MBNL, QKI, and RBFOX2 in a tissue-specific manner and is altered in striated muscle diseases.RNA biology · 2025Article
- A Live-Cell NanoBRET Assay to Monitor RNA-Protein Interactions and Their Inhibition by Small Molecules.ACS central science · 2025Article
- Multiple Defects in Muscle Regeneration in the HSALR Mouse Model of RNA Toxicity.International journal of molecular sciences · 2025Article
- The bidirectional interplay between RNA processing and mechanotransduction.Cell reports · 2025Review
- Repeat length as a key determinant for disease severity and antisense oligonucleotide activity in myotonic dystrophy type 1.Molecular therapy. Methods & clinical development · 2025Article
- Early Stage Morphogenesis of Transverse Tubules in Rat Cardiomyocytes: The Role of pBIN1.Circulation research · 2025Article
- Molecular genetics of myotonic dystrophy and the evolution of therapeutic approaches.Journal of human genetics · 2025Review
- Bend it like BIN1: how a membrane-curving adaptor protein shapes cardiac physiology.American journal of physiology. Heart and circulatory physiology · 2025Review
- MBNL deficiency in motor neurons disrupts neuromuscular junction maintenance and gait coordination.Brain : a journal of neurology · 2025Article
- Use of HSALab animal · 2025Article
- Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUGAntioxidants (Basel, Switzerland) · 2025Article
155 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 16 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myotonic dystrophy is the most common muscular dystrophy in adults and the first recognized example of an RNA-mediated disease. Congenital myotonic dystrophy (CDM1) and myotonic dystrophy of type 1 (DM1) or of type 2 (DM2) are caused by the expression of mutant RNAs containing expanded CUG or CCUG repeats, respectively. These mutant RNAs sequester the splicing regulator Muscleblind-like-1 (MBNL1), resulting in specific misregulation of the alternative splicing of other pre-mRNAs. We found that alternative splicing of the bridging integrator-1 (BIN1) pre-mRNA is altered in skeletal muscle samples of people with CDM1, DM1 and DM2. BIN1 is involved in tubular invaginations of membranes and is required for the biogenesis of muscle T tubules, which are specialized skeletal muscle membrane structures essential for excitation-contraction coupling. Mutations in the BIN1 gene cause centronuclear myopathy, which shares some histopathological features with myotonic dystrophy. We found that MBNL1 binds the BIN1 pre-mRNA and regulates its alternative splicing. BIN1 missplicing results in expression of an inactive form of BIN1 lacking phosphatidylinositol 5-phosphate-binding and membrane-tubulating activities. Consistent with a defect of BIN1, muscle T tubules are altered in people with myotonic dystrophy, and membrane structures are restored upon expression of the normal splicing form of BIN1 in muscle cells of such individuals. Finally, reproducing BIN1 splicing alteration in mice is sufficient to promote T tubule alterations and muscle weakness, a predominant feature of myotonic dystrophy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.