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Transposable Element RNAi Goes beyond Post-transcriptional Silencing: mRNA-Derived Small RNAs Both Regulate Genes and Initiate DNA Methylation

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서명/저자사항Transposable Element RNAi Goes beyond Post-transcriptional Silencing: mRNA-Derived Small RNAs Both Regulate Genes and Initiate DNA Methylation.
개인저자McCue, Andrea D.
단체저자명The Ohio State University. Molecular Genetics.
발행사항[S.l.]: The Ohio State University., 2015.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2015.
형태사항360 p.
기본자료 저록Dissertations Abstracts International 81-06B.
Dissertation Abstract International
ISBN9781392849910
학위논문주기Thesis (Ph.D.)--The Ohio State University, 2015.
일반주기 Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Advisor: Slotkin, R. Keith.
이용제한사항This item must not be sold to any third party vendors.
요약Transposable elements (TEs) are mobile genetic elements found in all branches of life. These parasitic elements' mobility make them potent mutagens. As such, recognition and silencing of TEs is crucial for the health and survival of their host organisms. All multicellular organisms avoid the detrimental effects of TE activity through repressive epigenetic modifications of the TE chromatin that heritably prevent TE transcription and, ultimately, transposition. These epigenetic alterations include cytosine DNA methylation, histone tail modifications, and chromatin condensation. I utilized the model genetic plant, Arabidopsis thaliana, to address the biological question of how organisms recognize actively transcribing TEs for heritable epigenetic silencing. I found that when TEs are transcriptionally active, an endogenous RNA interference pathway degrades TE mRNA into 21-22 nucleotide small RNAs. This degradation acts to repress TE activity and rein in TE replication. Additionally, I found that some of these small RNAs are able to regulate genic mRNA through their incorporation into the Argonaute1 protein and their complementarity to genic mRNAs. This mechanism of TE influence on non-neighboring genes is novel and was one of the first examples in the literature to directly demonstrate this mechanism. In addition to their role in TE and genic post-transcriptional regulation, I also identified a role for these small RNAs in the establishment of DNA methylation of actively transcribing TEs. Upon discovery of this pathway and its function, I further determined the molecular mechanism for this expression-dependent DNA methylation pathway. This finding represents a link between active TEs and their epigenetic silencing that had not existed before and provides a possible mechanism whereby novel TEs may be quickly and efficiently recognized for heritable epigenetic silencing.
일반주제명Genetics.
Molecular biology.
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