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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Dissection of Drosophila melanogaster Flight Muscles for Omics Approaches
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Alternative splicing diversifies the skeletal muscle transcriptome during prolonged spaceflight.

Mason Henrich1, Pin Ha2, Yuanyuan Wang3

  • 1Department of Molecular, Cell & Developmental Biology, University of California, 615 Charles E Young Dr S Room 446, Los Angeles, CA, 90095, USA. mhenrich@g.ucla.edu.

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Spaceflight alters skeletal muscle by changing gene expression and splicing. Differential alternative splicing, not just differential gene expression, impacts muscle atrophy and fiber type during space missions.

Keywords:
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Area of Science:

  • Space biology
  • Molecular biology
  • Skeletal muscle physiology

Background:

  • Manned spaceflight increases the need to understand skeletal muscle adaptations to microgravity.
  • Differential gene expression (DGE) in microgravity is well-studied, but differential alternative splicing (DAS) is not.
  • This study investigates both DGE and DAS in skeletal muscle during spaceflight.

Purpose of the Study:

  • To comprehensively characterize the skeletal muscle transcriptome during microgravity exposure.
  • To investigate the roles of both differential gene expression (DGE) and differential alternative splicing (DAS) in microgravity-induced skeletal muscle changes.
  • To provide insights into molecular mechanisms underlying muscle plasticity in space.

Main Methods:

  • RNA-sequencing, immunohistochemistry, and morphological analyses were performed.
  • Samples were from gastrocnemius and quadriceps muscles of female BALB/c mice.
  • Mice were exposed to 9 weeks of microgravity or ground control conditions.

Main Results:

  • Microgravity remodeled the skeletal muscle transcriptome through both DGE and DAS.
  • DAS, unlike DGE, enriched structural and functional gene networks, affecting muscle atrophy and fiber type.
  • RNA-binding proteins showed differential splicing but not differential expression, suggesting an upstream regulatory mechanism.

Conclusions:

  • This is the first study to examine coordinated DGE and DAS in limb muscles during spaceflight.
  • It offers new understanding of how splice variants regulate microgravity adaptations in skeletal muscle.
  • It highlights potential for splicing regulator therapies to mitigate muscle atrophy and fiber type changes in astronauts.