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Role of long non coding RNA in muscle differentiation and disease

Final Report Summary - MUNCODD (Role of long non coding RNA in muscle differentiation and disease)

The central dogma of molecular biology that genes act as a template for protein production is now a thing of the past. In the post-genomic era, a careful examination in different animal species of which DNA sequences are transcribed in RNA, has opened an interesting debate on the exact definition of a gene and the relationship between the number of genes and the biological complexity of a higher organism. The discovery of a large number of RNA molecules that do not code for proteins has provided an important and new perspective on the role of RNA in gene regulation. The analysis of all cell transcripts has in fact shown that the fraction of the genome that is used as template for proteins is limited 1-2%, while non-coding RNAs are much more abundant. Nonetheless, most of this unannotated transcription remains to be characterized.
The MUNCODD project has allowed to identify the entire repertoire of non coding RNAs that are expressed during human and murine myogenesis and to attribute specific functions to several of these species in the control of muscle differentiation and homeostasis, including the heart. Through the study of non canonical RNA species, we were also able to characterize a novel class of transcripts with a peculiar circular structure (circRNAs) and to show that they too play crucial functions in myogenesis.
Finally, MUNCODD identified a novel possible approach for the therapy of Duchenne Muscular Dystrophy (DMD). Through the study of a DMD patient, we discovered that the ablation of a specific splicing factor (Celf2a) can become curative for those patients where skipping of exon 45 can rescue dystrophin production. In more general terms this study also points to the relevance of studying the genomic milieu of different patients in order to facilitate the clinical development of personalized therapies.