Constitutive and regulated modes of splicing produce six major myotonic dystrophy protein kinase (DMPK) isoforms with distinct properties
| العنوان: | Constitutive and regulated modes of splicing produce six major myotonic dystrophy protein kinase (DMPK) isoforms with distinct properties |
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| المؤلفون: | Derick G. Wansink, W.J.A.A. van den Broek, Marga Coerwinkel, Bé Wieringa, G Jansen, Patricia J. T. A. Groenen |
| المصدر: | Human Molecular Genetics, 9, 4, pp. 605-616 Human Molecular Genetics, 9, 605-616 |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | Protein isoform, Untranslated region, Male, Immunologische ontstekingsprocessen in de nier, DNA, Complementary, Pathobiologische rol van myotone dystrofie protein kinase isovormen, Mice, Transgenic, Biology, Protein Serine-Threonine Kinases, Myotonic dystrophy, Myotonin-Protein Kinase, Frameshift mutation, Exon, Mice, Inflammatory reactions in the kidneys, Genetics, medicine, Animals, Humans, Myotonic Dystrophy, RNA, Messenger, Transgenes, Molecular Biology, Genetics (clinical), Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Myotonin-protein kinase, Alternative splicing, General Medicine, Exons, medicine.disease, Molecular biology, Isoenzymes, Pathobiological role of myotonic dystrophy protein kinase isoforms, Alternative Splicing, RNA splicing, COS Cells, Protein Processing, Post-Translational |
| الوصف: | Myotonic dystrophy (DM) is the most prevalent inherited neuromuscular disease in adults. The genetic defect is a CTG triplet repeat expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase ( DMPK ) gene, consisting of 15 exons. Using a transgenic DMPK-overexpressor mouse model, we demonstrate here that the endogenous mouse DMPK gene and the human DMPK transgene produce six major alternatively spliced mRNAs which have almost identical cell type-dependent distribution frequencies and expression patterns. Use of a cryptic 5' splice site in exon 8, which results in absence or presence of 15 nucleotides specifying a VSGGG peptide motif, and/or use of a cryptic 3' splice site in exon 14, which leads to a frameshift in the mRNA reading frame, occur as independent stochastic events in all tissues examined. In contrast, the excision of exons 13/14 that causes a frameshift and creates a C-terminally truncated protein is clearly cell type dependent and occurs predominantly in smooth muscle. We generated all six full-length mouse cDNAs that result from combinations of these three major splicing events and show that their transfection into cells in culture leads to production of four different approximately 74 kDa full-length (heart-, skeletal muscle- or brain-specific) and two C-terminally truncated approximately 68 kDa (smooth muscle-specific) isoforms. Information on DMPK mRNA and protein isoform expression patterns will be useful for recognizing differential effects of (CTG)(n)expansion in DM manifestation. |
| تدمد: | 0964-6906 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f45c36aa7692176a8117187c7076d7ed https://pubmed.ncbi.nlm.nih.gov/10699184 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f45c36aa7692176a8117187c7076d7ed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09646906 |
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