Document Type


Date of Degree

Spring 2013

Degree Name

PhD (Doctor of Philosophy)

Degree In

Molecular and Cellular Biology

First Advisor

Davidson, Beverly L

First Committee Member

Dupuy, Adam

Second Committee Member

Logsdon, John

Third Committee Member

Russo, Andrew

Fourth Committee Member

Xing, Yi


MicroRNAs (miRNAs) are an abundant and diverse class of small, non-protein coding RNAs that guide the post-transcriptional repression of messenger RNA (mRNA) targets in a sequence-specific manner. Hundreds, if not thousands of distinct miRNA sequences have been described, each of which has the potential to regulate a large number of mRNAs. Over the last decade, miRNAs have been ascribed roles in nearly all biological processes in which they have been tested. More recently, interest has grown in understanding how individual miRNAs evolved, and how they are regulated. In this work, we demonstrate that Transposable Elements are a source for novel miRNA genes and miRNA target sites. We find that primate-specific miRNA binding sites were gained through the transposition of Alu elements. We also find that remnants of Mammalian Interspersed Repeat transposition, which occurred early in mammalian evolution, provide highly conserved functional miRNA binding sites in the human genome. We also provide data to support that long non-coding RNAs (lncRNAs) can provide a novel miRNA binding substrate which, rather than inhibiting the miRNA target, inhibits the miRNA. As such, lncRNAs are proposed to function as endogenous miRNA "sponges," competing for miRNA binding and reducing miRNA-mediated repression of protein-coding mRNA targets. We also explored how dynamic changes to miRNA binding sites can occur by A-to-I editing of the 3 `UTRs of mRNA targets. These works, together with knowledge gained from the regulatory activity of endogenous and exogenously added miRNAs, provided a platform for algorithm development that can be used in the rational design of artificial RNAi triggers with improved target specificity. The cumulative results from our studies identify and in some cases clarify important mechanisms for the emergence of miRNAs and miRNA binding sites on large (over eons) and small (developmental) time scales, and help in translating these gene silencing processes into practical application.


lincRNA, lncRNA, microRNA, RNAi, Transposable Element, Transposon


xii, 146 pages


Includes bibliographical references (pages 130-146).


Copyright 2013 Ryan Spengler

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Cell Biology Commons