4.7 Article

microRNA-mRNA Profile of Skeletal Muscle Differentiation and Relevance to Congenital Myotonic Dystrophy

Journal

Publisher

MDPI
DOI: 10.3390/ijms22052692

Keywords

microRNA; muscle differentiation; congenital myotonic dystrophy

Funding

  1. American Academy of Pediatrics Marshall Klaus Perinatal Research Award [R01-AR068429-01]
  2. National Institute of Arthritis and Musculoskeletal and Skin Diseases of National Institute of Health (NIH)

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miRNAs play a key role in regulating mRNA during processes like muscle differentiation. Understanding miRNA targets can provide insights into muscle biology and gene expression changes caused by diseases. The study found that differentially expressed miRNAs are enriched for functions related to calcium signaling and sarcomere formation.
microRNAs (miRNAs) regulate messenger RNA (mRNA) abundance and translation during key developmental processes including muscle differentiation. Assessment of miRNA targets can provide insight into muscle biology and gene expression profiles altered by disease. mRNA and miRNA libraries were generated from C2C12 myoblasts during differentiation, and predicted miRNA targets were identified based on presence of miRNA binding sites and reciprocal expression. Seventeen miRNAs were differentially expressed at all time intervals (comparing days 0, 2, and 5) of differentiation. mRNA targets of differentially expressed miRNAs were enriched for functions related to calcium signaling and sarcomere formation. To evaluate this relationship in a disease state, we evaluated the miRNAs differentially expressed in human congenital myotonic dystrophy (CMD) myoblasts and compared with normal control. Seventy-four miRNAs were differentially expressed during healthy human myocyte maturation, of which only 12 were also up- or downregulated in CMD patient cells. The 62 miRNAs that were only differentially expressed in healthy cells were compared with differentiating C2C12 cells. Eighteen of the 62 were conserved in mouse and up- or down-regulated during mouse myoblast differentiation, and their C2C12 targets were enriched for functions related to muscle differentiation and contraction.

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