Date of Graduation

5-2015

Document Type

Thesis

Degree Name

Master of Science in Kinesiology (MS)

Degree Level

Graduate

Department

Health, Human Performance and Recreation

Advisor/Mentor

Greene, Nicholas P.

Committee Member

Washington, Tyrone A.

Second Committee Member

Bottje, Walter G.

Keywords

Biological sciences; Health and environmental sciences; Mitochondria; Protein synthesis; Skeletal muscle; microRNAs

Abstract

microRNA (miRNA) post-transcriptional modification is becoming a well-established mechanism for controlling mRNA translation. microRNAs -1, -133, and -206 are under the control of skeletal muscle promoters and affect muscle plasticity and metabolic health. A detailed review on the generation and processing of miRNAs with a view to skeletal muscle brings up intriguing connections in the transcriptional connections between multiple miRNAs. Additionally, exciting new research has defined a role of miRNAs in skeletal muscle mitochondria showing an additional, direct link to metabolic function. Multiple investigations in models of exercise, aging, hypertrophy, and injury have shown how these interventions can affect miRNA content and activity. Because skeletal muscle is such an abundant and metabolically active tissue, it is important to understand its detailed physiology. Individual overexpression of miR -1 resulted in ~25% less phosphorylation of Akt and phosphorylation of p70S6K1 but did not change overall basal protein synthesis. These same measures of protein synthetic signaling were unaltered in cells overexpressing miR-133b. Additionally, gene and protein contents of COX-IV, a surrogate measure of mitochondrial content, were higher in both miR-1 (~100%) and -133b (~45%) overexpressed cells. Additionally, any change in mitochondrial content was separate from TFAM or PGC-1α protein as neither was changed by miR-1 or -133 overexpression. Together, these results indicate a clear advancement in the knowledge of the effects miRs -1 and -133 have on protein synthesis and on the mitochondrial network by taking clear steps towards understanding the effects of miRs -1 and -133b on protein synthesis and the mitochondrial network through assessment of mitochondrial content and turnover.

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