the dmd locus harbours multiple long non-coding rnas which orchestrate and control transcription of muscle dystrophin mrna isoformsdmd轨迹港口多个长非编码rna编排和控制肌肉的肌营养不良蛋白mrna转录亚型.pdf

The DMD Locus Harbours Multiple Long Non-Coding RNAs Which Orchestrate and Control Transcription of Muscle Dystrophin mRNA Isoforms 1. 2. 2 1 1 Matteo Bovolenta , Daniela Erriquez , Emanuele Valli , Simona Brioschi , Chiara Scotton , 1 1 3 1 1 Marcella Neri , Maria Sofia Falzarano , Samuele Gherardi , Marina Fabris , Paola Rimessi , 1 3 1 Francesca Gualandi , Giovanni Perini , Alessandra Ferlini * 1 Department of Medical Science, Section of Medical Genetics, University of Ferrara, Ferrara, Italy, 2 Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy, 3 Department of Pharmacy and Biotechnology, Health Sciences and Technologies – Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Bologna, Italy Abstract The 2.2 Mb long dystrophin (DMD) gene, the largest gene in the human genome, corresponds to roughly 0.1% of the entire human DNA sequence. Mutations in this gene cause Duchenne muscular dystrophy and other milder X-linked, recessive dystrophinopathies. Using a custom-made tiling array, specifically designed for the DMD locus, we identified a variety of novel long non-coding RNAs (lncRNAs), both sense and antisense oriented, whose expression profiles mirror that of DMD gene. Importantly, these transcripts are intronic in origin and specifically localized to the nucleus and are transcribed contextually with dystrophin isoforms or primed by MyoD-induced myogenic differentiation. Furthermore, their forced ectopic expression in both human