Date of Award

Spring 1-1-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Leslie A. Leinwand

Second Advisor

Bradley B. Olwin

Third Advisor

Kenneth S. Krauter

Fourth Advisor

Rui Yi

Fifth Advisor

Donald D. Heistad

Abstract

Skeletal muscle is a remarkable organ system that is required for almost all animal life. In vertebrates, skeletal muscle can alter its functional and molecular characteristics in response to pathologic and physiologic stimuli. Additionally, adult muscle retains the ability to regenerate following injury, activating progenitor cells much like the process of muscle formation during embryonic development. Much work has been done to characterize the changes in gene expression that occur during regeneration, and this knowledge has been invaluable in treatment of muscle wasting diseases, such as Duchenne Muscular Dystrophy. Further expanding the complexity of gene expression changes is the discovery that most genes are subject to post-transcriptional regulation by microRNAs (miRNAs). In this thesis, I present two data chapters that explore miRNA function during skeletal myogenesis. In the first, I discuss a novel method for the measurement of miRNA activity using bioluminescent imaging in vivo. This study provides future investigators with a tool to follow the activity of miRNAs during muscle remodeling in vivo. In the second, I present a miRNA expression profiling experiment that identified the down-regulation of an abundant miRNA family, miR-30. I also go on to show that these miRNAs play a key molecular role in the process of myogenesis by regulating epigenetic, transcriptional and post-transcriptional control of gene expression.

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