title: Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy.
abstract: Myotonic dystrophy (DM) is caused by a CTG expansion in the 3' untranslated region of the DM gene. One model of DM pathogenesis suggests that RNAs from the expanded allele create a gain-of-function mutation by the inappropriate binding of proteins to the CUG repeats. Data presented here indicate that the conserved heterogeneous nuclear ribonucleoprotein, CUG-binding protein (CUG-BP), may mediate the trans-dominant effect of the RNA. CUG-BP was found to bind to the human cardiac troponin T (cTNT) pre-messenger RNA and regulate its alternative splicing. Splicing of cTNT was disrupted in DM striated muscle and in normal cells expressing transcripts that contain CUG repeats. Altered expression of genes regulated posttranscriptionally by CUG-BP therefore may contribute to DM pathogenesis.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Philips
authors.forename: L T
authors.initials: LT
authors.lastname: Timchenko
authors.forename: T A
authors.initials: TA
authors.lastname: Cooper
mesh_terms: D017398:Alternative Splicing; D000067879:CELF1 Protein; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005091:Exons; D006801:Humans; D007438:Introns; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000378:metabolism; D065636:Myotonin-Protein Kinase; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D018911:Trinucleotide Repeats; D014336:Troponin / Q000235:genetics; D020107:Troponin T
chemical_list: D000067879:CELF1 Protein; C102843:CELF1 protein, human; C585517:DMPK protein, human; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D014336:Troponin; D020107:Troponin T; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases