Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Biology, Molecular and Cellular Biology

Date of Defense

12-12-2016

Graduate Advisor

Mindy Steiniger, PhD.

Committee

Dr. Mindy Steiniger

Dr. Bethany Zolman

Dr. Wendy Olivas

Dr. Michael Hughes

Abstract

Rarely in research is the path to an answer straightforward. Initial questions lead to more questions, many times doubling back to allow for greater insight into the original question. For example, discovery of interactions between previously unrelated pathways can lead to breakthroughs with regard to understanding of gene regulation. One such novel interaction and the subsequent discoveries this interaction spurred are discussed herein. Transposons, or “Jumping Genes” are mobile genetic elements found throughout all three major domains of life. Transposons comprise 44% of the human genome and possess the ability to move within the genome. This ability makes them an important driver of evolution, but also requires that they be tightly regulated. In 2008, a number of papers were published outlining a new class of small RNA, endogenous small interfering RNA (esiRNA). These esiRNAs were derived from transposons and structured loci (hairpins.) EsiRNAs are produced from a dsRNA precursor in a Dicer-2 dependent manner. When a novel interaction between the 3’ end processing factor Symplekin and Dicer-2 was discovered, further investigation into this relationship, and the very nature of esiRNA precursors was warranted. Herein, I uncover the mechanism by which certain classes of transposons create the dsRNA precursor necessary for esiRNA biogenesis and shed light onto their regulation. I further investigate the difference between retrotransposons or hairpin derived esiRNAs with regard to their physical characteristics and subcellular location. Lastly, I investigate the role 3’ end processing machinery, such as Symplekin, plays in esiRNA biogenesis.

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