Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by frameshift mutations in the dystrophin gene. Among the molecular mechanisms potentially involved in DMD, we focused our attention on microRNAs (miRNAs) a new class of gene-expression regulators. The identification of new predicted miRNAs in dystrophin gene could evidence a molecular network specific for DMD. To predict the presence of pre-miRNA in the dystrophin gene, we analyzed its genomic sequence with three microRNA-gene prediction algorithms (mirEval, mirFinder and MiR-abela) which analyze criteria such as the secondary structure and free-folding energy of their precursors, conservation of part of the miRNA sequence or similarity with other miRNAs and since miRNA are occasionally found in clusters, analysis of genomic regions around already known miRNA. A set of 28 pre-miRNAs were predicted to be encoded within the dystrophin gene. The various predictions were compared considering the localization and the structure of the predicted stem loops; 14 of them were resulted in common to all three algorithms. Sequences of predicted miRNA were checked in miRbase and aligned with known stem-loop precursors and mature miRNAs. This analysis evidenced that five putative pre-miRNA showed significant similarity with known miRNAs thus letting suppose that the dystrophin gene could contain new transcription sites for annotated miRNAs. The remaining 23 predictions did not show any alignment with already validated miRNAs and could represent new miRNA molecules. Validation of these predicted miRNAs within dystrophin gene will add new intrinsic molecular networks to the characterization of DMD pathogenesis and could explain the variability of the DMD clinical phenotypes. However, all these findings raise the opportunity for therapeutic intervention at the miRNA level preventing specific pathways underlying this muscle disease. This work has been supported by the Associazione Amici del Centro Dino Ferrari, the Association Monégasque contre les Myopathies, Optistem 223098 and the Associazione La Nostra Famiglia Fondo DMD Gli Amici di Emanuele. MiRNA-dysregulation in dystrophic single fibers
Predicted miRNAs in murine dystrophin gene / M.L. Cassinelli, S. Maciotta, F. Gandolfi, M. Forcato, S. Bocciato, M. Meregalli, Y. Torrente. ((Intervento presentato al convegno Keystone Symposia, Epigenomics Keystone tenutosi a Colorado USA nel 2012.
|Titolo:||Predicted miRNAs in murine dystrophin gene|
|Data di pubblicazione:||gen-2012|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Citazione:||Predicted miRNAs in murine dystrophin gene / M.L. Cassinelli, S. Maciotta, F. Gandolfi, M. Forcato, S. Bocciato, M. Meregalli, Y. Torrente. ((Intervento presentato al convegno Keystone Symposia, Epigenomics Keystone tenutosi a Colorado USA nel 2012.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|