Extensive alternative splicing transitions during postnatal skeletal muscle development are required for Ca2+ handling
- Baylor College of Medicine, United States
Abstract
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 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.
Article and author information
Author details
Funding
National Institutes of Health (R01AR045653)
- Thomas A Cooper
Muscular Dystrophy Association (RG4205)
- Thomas A Cooper
National Institutes of Health (R01HL045565)
- Thomas A Cooper
National Institutes of Health (R01AR060733)
- Thomas A Cooper
National Institutes of Health (T32 HL007676)
- James Anthony Loehr
National Institutes of Health (R01HG007538)
- Wei Li
National Institutes of Health (R01CA193466)
- Wei Li
National Institutes of Health (R01AR061370)
- George Gerald Rodney
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animals were handled following the NIH Guidelines for Use and Care of Laboratory Animals that were approved by the Institutional Animal Care and Use Committee (IACUC) at Baylor College of Medicine, protocol AN-1682).
Copyright
© 2017, Brinegar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Extensive alternative splicing transitions during postnatal skeletal muscle development are required for Ca2+ handling
eLife 6:e27192.
https://doi.org/10.7554/eLife.27192
