Document Type

Campus-Only Access for Five (5) Years

Embargo Period

8-25-2016

Degree Program

Molecular & Cellular Biology

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2016

Month Degree Awarded

September

Advisor Name

Lawrence

Advisor Middle Initial

M.

Advisor Last Name

Schwartz

Co-advisor Name

Li-Jun

Co-advisor Last Name

Ma

Third Advisor Name

Leonid

Third Advisor Middle Initial

A.

Third Advisor Last Name

Pobezinsky

Abstract

A variety of diseases lead to the atrophy and/or death of skeletal muscle. To better understand the molecular mechanisms that mediate these processes, I have taken advantage of the intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta, which undergo sequential programs of atrophy and programmed cell death at the end of metamorphosis. ISM death is mediated by changes in gene expression and numerous cell-death associated transcripts have been identified. MicroRNAs (miRs) are small (~22 nucleotide) non-coding RNAs that bind to sequences in messenger RNAs (mRNAs) and either cause translational arrest or mRNA degradation. To test the hypothesis that developmentally regulated miRs may control the stability and/or translatability of target mRNAs in the ISMs, putative mRNA targets for the test miRs have been identified and their 3’ untranslated region (UTR) have been cloned into a dual luciferase reporter plasmid. The microRNA mir-92b binds to the 3’ UTR of the Small Cytoplasmic Leucine Rich repeat Protein (SCLP) mRNA. Expression of miR-92b declines during development and SCLP expression increases with the commitment to die. I found that the miR-92b inhibits luciferase mRNA translation (spectrophotometric plate assays), but does not lead to transcript degradation (quantitative polymerase chain reaction; qPCR). miR-92 plays a survival role in several mammalian tissues and is repressed in two types of cardiomyopathy. Consequently, understanding how miRs regulate mRNA translation and stability may provide a better understanding of the regulation of muscle atrophy and death as well as provide novel tools for diagnostics or therapeutics.

First Advisor

Lawrence M. Schwartz

Second Advisor

Li-jun Ma

Third Advisor

Leonid A. Pobezinsky

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