ZNF9 Activation of IRES-Mediated Translation of the Human ODC mRNA Is Decreased in Myotonic Dystrophy Type 2
| العنوان: | ZNF9 Activation of IRES-Mediated Translation of the Human ODC mRNA Is Decreased in Myotonic Dystrophy Type 2 |
|---|---|
| المؤلفون: | Bjarne Udd, Morgan A. Sammons, Andrew J. Link, Amanda K. Antons, Mourad Bendjennat, Ralf Krahe |
| المساهمون: | University of Tampere, Department of Medical and Clinical Genetics |
| المصدر: | PLoS ONE PLoS ONE, Vol 5, Iss 2, p e9301 (2010) |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | TRANS-ACTING FACTORS, lcsh:Medicine, RNA-binding protein, Myoblasts, 0302 clinical medicine, Neurologia ja psykiatria - Neurology and psychiatry, Protein biosynthesis, 311 Basic medicine, Myotonic Dystrophy, Muscular dystrophy, lcsh:Science, IN-VIVO, Neurological Disorders/Movement Disorders, Cells, Cultured, 0303 health sciences, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, EXPANDED-REPEAT TRANSCRIPTS, RNA-Binding Proteins, PROTEIN TRANSLATION, LA PROTEIN, RNA Interference, CUG REPEATS, Biochemistry/Transcription and Translation, Research Article, Protein Binding, EXPRESSION, RNA Caps, musculoskeletal diseases, DM2, education, Blotting, Western, Neurological Disorders/Neuromuscular Diseases, Biology, Ornithine Decarboxylase, Myotonic dystrophy, Cell Line, 03 medical and health sciences, Polysome, medicine, Biochemistry/RNA Structure, Humans, RNA, Messenger, Cell Biology/Gene Expression, 030304 developmental biology, Messenger RNA, Binding Sites, lcsh:R, Intron, MASS-SPECTROMETRY, medicine.disease, Molecular biology, Internal ribosome entry site, Protein Biosynthesis, T-CELLS, lcsh:Q, 5' Untranslated Regions, Ribosomes, 030217 neurology & neurosurgery, HeLa Cells |
| الوصف: | Myotonic dystrophy types 1 and 2 (DM1 and DM2) are forms of muscular dystrophy that share similar clinical and molecular manifestations, such as myotonia, muscle weakness, cardiac anomalies, cataracts, and the presence of defined RNA-containing foci in muscle nuclei. DM2 is caused by an expansion of the tetranucleotide CCTG repeat within the first intron of ZNF9, although the mechanism by which the expanded nucleotide repeat causes the debilitating symptoms of DM2 is unclear. Conflicting studies have led to two models for the mechanisms leading to the problems associated with DM2. First, a gain-of-function disease model hypothesizes that the repeat expansions in the transcribed RNA do not directly affect ZNF9 function. Instead repeat-containing RNAs are thought to sequester proteins in the nucleus, causing misregulation of normal cellular processes. In the alternative model, the repeat expansions impair ZNF9 function and lead to a decrease in the level of translation. Here we examine the normal in vivo function of ZNF9. We report that ZNF9 associates with actively translating ribosomes and functions as an activator of cap-independent translation of the human ODC mRNA. This activity is mediated by direct binding of ZNF9 to the internal ribosome entry site sequence (IRES) within the 5′UTR of ODC mRNA. ZNF9 can activate IRES-mediated translation of ODC within primary human myoblasts, and this activity is reduced in myoblasts derived from a DM2 patient. These data identify ZNF9 as a regulator of cap-independent translation and indicate that ZNF9 activity may contribute mechanistically to the myotonic dystrophy type 2 phenotype. Public Library of Science |
| وصف الملف: | fulltext |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0cc9b0d058694acd46d7488489f4981 https://trepo.tuni.fi/handle/10024/65935 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f0cc9b0d058694acd46d7488489f4981 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |