Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions

Amy E. Brinegar, Zheng Xia, James Anthony Loehr, Wei Li, George Gerald Rodney, Thomas A. Cooper

Research output: Research - peer-reviewArticle

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 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.

LanguageEnglish (US)
Article numbere27192
JournaleLife
Volume6
DOIs
StatePublished - Aug 11 2017

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Muscle Development
Calcineurin
Alternative Splicing
Skeletal Muscle
Calcium
Muscles
Muscle
Protein Isoforms
Genes
vif Genes
Muscle Relaxation
Transcriptome
Phosphoric Monoester Hydrolases
Parturition
RNA
Gene Expression
Physiology
Transcription
Gene expression
Tissue

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions. / Brinegar, Amy E.; Xia, Zheng; Loehr, James Anthony; Li, Wei; Rodney, George Gerald; Cooper, Thomas A.

In: eLife, Vol. 6, e27192, 11.08.2017.

Research output: Research - peer-reviewArticle

Brinegar, Amy E. ; Xia, Zheng ; Loehr, James Anthony ; Li, Wei ; Rodney, George Gerald ; Cooper, Thomas A./ Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions. In: eLife. 2017 ; Vol. 6.
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