Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice. (3rd September 2018)

• Record Type: Journal Article
• Authors: Ballarino, Monica; Cipriano, Andrea; Tita, Rossella; Santini, Tiziana; Desideri, Fabio; Morlando, Mariangela; Colantoni, Alessio; Carrieri, Claudia; Nicoletti, Carmine; Musarò, Antonio; Carroll, Dònal O'; Bozzoni, Irene
• Is Part Of: EMBO journal. Volume 37:Number 18(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-03
• Subjects: CRISPR/Cas9 -- epigenetic control -- heart development -- lncRNAs -- myogenesis; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201899697
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: Myogenesis is a highly regulated process that involves the conversion of progenitor cells into multinucleated myofibers. Besides proteins and miRNAs, long noncoding RNAs (lncRNAs) have been shown to participate in myogenic regulatory circuitries. Here, we characterize a murine chromatin‐associated muscle‐specific lncRNA, Charme, which contributes to the robustness of the myogenic program in vitro and in vivo . In myocytes, Charme depletion triggers the disassembly of a specific chromosomal domain and the downregulation of myogenic genes contained therein. Notably, several Charme ‐sensitive genes are associated with human cardiomyopathies and Charme depletion in mice results in a peculiar cardiac remodeling phenotype with changes in size, structure, and shape of the heart. Moreover, the existence of an orthologous transcript in human, regulating the same subset of target genes, suggests an important and evolutionarily conserved function for Charme . Altogether, these data describe a new example of a chromatin‐associated lncRNA regulating the robustness of skeletal and cardiac myogenesis. Synopsis: The study characterises the chromatin‐associated long noncoding RNA (lncRNA) Charme, a novel murine muscle‐specific lncRNA conserved in human. Depletion studies in vitro and in vivo show that Charme regulates myogenesis by stabilising long‐range chromosomal interactions required to control the expression of pro‐myogenic loci. Charme is a novel chromatin‐associated muscle‐specific lncRNA. Charme regulates the robustness of skeletal and cardiac myogenesis by controlling the chromosomal architecture of pro‐myogenic genomic loci. Functional depletion of Charme in mice results in a severe cardiac phenotype and leads to lifespan reduction. Abstract : By inserting an artificial polyadenylation site in vivo, this study shows that expression of a specific lncRNA is required for local chromatin organisation and normal cardiac development.