| First Author | Brinegar AE | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28826478 | Mgi Jnum | J:256956 |
| Mgi Id | MGI:6117002 | Doi | 10.7554/eLife.27192 |
| Citation | Brinegar AE, et al. (2017) Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions. Elife 6:e27192 |
| abstractText | 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 2 weeks after birth are particularly dynamic for differential gene expression and alternative splicing transitions, and calcium-handling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of the 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 target Nfatc3, and/or affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of alternative splicing during muscle postnatal development. |
