Abstract
Gene differential expression and alternative splicing are mechanisms that give rise to a plethora of tissue-specific transcripts. Although these mechanisms have been studied in various tissues, their role during muscle maturation is not well understood. Because this stage of development is impaired in multiple muscular diseases, we used RNA sequencing to analyze transcriptome remodeling in skeletal muscle from late embryonic stage [embryonic day (E)18.5] to adult mice (7 weeks). Major transcriptomic changes were detected, especially in the first 2 weeks after birth, with a total of 8571 differentially expressed genes and 3096 alternatively spliced genes. Comparison of the two mechanisms showed that they regulate different biological processes essential for the structure and function of skeletal muscle. Investigation of genes mutated in muscle disorders revealed previously unknown transcripts. In particular, we validated a novel exon in Lrp4, a gene mutated in congenital myasthenia, in mice and humans. Overall, the characterization of the transcriptome in disease-relevant tissues revealed key pathways in the regulation of tissue maturation and function. Importantly, the exhaustive description of alternative splicing and resulting transcripts can improve genetic diagnosis of muscular diseases.