Stretching muscle cells induces transcriptional and splicing transitions and changes in SR proteins View Full Text


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Article Info

DATE

2022-09-19

AUTHORS

Emma R. Hinkle, R. Eric Blue, Yi-Hsuan Tsai, Matthew Combs, Jacquelyn Davi, Alisha R. Coffey, Aladin M. Boriek, Joan M. Taylor, Joel S. Parker, Jimena Giudice

ABSTRACT

Alternative splicing is an RNA processing mechanism involved in skeletal muscle development and pathology. Muscular diseases exhibit splicing alterations and changes in mechanobiology leading us to investigate the interconnection between mechanical forces and RNA processing. We performed deep RNA-sequencing after stretching muscle cells. First, we uncovered transcriptional changes in genes encoding proteins involved in muscle function and transcription. Second, we observed that numerous mechanosensitive genes were part of the MAPK pathway which was activated in response to stretching. Third, we revealed that stretching skeletal muscle cells increased the proportion of alternatively spliced cassette exons and their inclusion. Fourth, we demonstrated that the serine and arginine-rich proteins exhibited stronger transcriptional changes than other RNA-binding proteins and that SRSF4 phosphorylation is mechanosensitive. Identifying SRSF4 as a mechanosensitive RNA-binding protein that might contribute to crosstalk between mechanotransduction, transcription, and splicing could potentially reveal novel insights into muscular diseases, particularly those with unknown etiologies. More... »

PAGES

987

References to SciGraph publications

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  • 2012-04-19. Challenges in estimating percent inclusion of alternatively spliced junctions from RNA-seq data in BMC BIOINFORMATICS
  • 2009-10-27. The SR protein family in GENOME BIOLOGY
  • 2011-05-29. Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy in NATURE MEDICINE
  • 2017-07-31. Genetic mutations in RNA-binding proteins and their roles in ALS in HUMAN GENETICS
  • 2013-03-24. Regulation of splicing by SR proteins and SR protein-specific kinases in CHROMOSOMA
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  • 2018-03-06. Diversification of the muscle proteome through alternative splicing in SKELETAL MUSCLE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s42003-022-03915-7

    DOI

    http://dx.doi.org/10.1038/s42003-022-03915-7

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/36123433


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    29 schema:description Alternative splicing is an RNA processing mechanism involved in skeletal muscle development and pathology. Muscular diseases exhibit splicing alterations and changes in mechanobiology leading us to investigate the interconnection between mechanical forces and RNA processing. We performed deep RNA-sequencing after stretching muscle cells. First, we uncovered transcriptional changes in genes encoding proteins involved in muscle function and transcription. Second, we observed that numerous mechanosensitive genes were part of the MAPK pathway which was activated in response to stretching. Third, we revealed that stretching skeletal muscle cells increased the proportion of alternatively spliced cassette exons and their inclusion. Fourth, we demonstrated that the serine and arginine-rich proteins exhibited stronger transcriptional changes than other RNA-binding proteins and that SRSF4 phosphorylation is mechanosensitive. Identifying SRSF4 as a mechanosensitive RNA-binding protein that might contribute to crosstalk between mechanotransduction, transcription, and splicing could potentially reveal novel insights into muscular diseases, particularly those with unknown etiologies.
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