PT - JOURNAL ARTICLE AU - Amy E. Brinegar AU - Zheng Xia AU - James A. Loehr AU - Wei Li AU - George G. Rodney AU - Thomas A. Cooper TI - Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions AID - 10.1101/124230 DP - 2017 Jan 01 TA - bioRxiv PG - 124230 4099 - http://biorxiv.org/content/early/2017/04/05/124230.short 4100 - http://biorxiv.org/content/early/2017/04/05/124230.full AB - Postnatal development of skeletal muscle is a highly dynamic period of tissue remodeling. Here we used RNA-seq to identify transcriptome changes from late embryonic to adult mouse muscle and demonstrate that alternative splicing developmental transitions impact muscle physiology. The first two weeks after birth are particularly dynamic for differential gene expression and AS transitions, and calciumhandling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of three calcineurin A genes, calcium-dependent phosphatases that regulate multiple aspects of muscle biology. Redirected splicing of calcineurin A to the fetal isoforms in adult muscle and in differentiated C2C12 slows the timing of muscle relaxation, promotes nuclear localization of calcineurin targets Nfatc3 and Nfatc2, and affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of AS during muscle postnatal development.