Atanasov, Janina (2017)
Design and implementation of a synthetic pre-miR switch for controlling miRNA biogenesis in mammals.
Technische Universität Darmstadt
Ph.D. Thesis, Primary publication
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genehmigte Dissertation Janina Atanasov_FB10.pdf Copyright Information: CC BY 4.0 International - Creative Commons, Attribution. Download (5MB) | Preview |
Item Type: | Ph.D. Thesis | ||||
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Type of entry: | Primary publication | ||||
Title: | Design and implementation of a synthetic pre-miR switch for controlling miRNA biogenesis in mammals | ||||
Language: | English | ||||
Referees: | Süß, Prof. Dr. Beatrix ; Löwer, Prof. Dr. Alexander | ||||
Date: | 30 March 2017 | ||||
Place of Publication: | Darmstadt | ||||
Date of oral examination: | 28 March 2017 | ||||
Abstract: | In this study a natural miRNA precursor was modified by replacing the natural terminal loop with a regulatory sensor domain, the TetR-binding aptamer to enable the ligand-dependent control of the processing of miRNA precursor to mature miRNAs. The TetR aptamer was positioned close to the Dicer cleavage sites, which allowed sterical control over pre-miR processing by Dicer. The design proved to be widely applicable, allowing to regulate the biogenesis of three structurally different miRNAs: miR-126, -34a and -199a. Dicer cleavage could be inhibited up to 143-fold via co-expression of the TetR protein, yet could be completely restored upon addition of doxycycline. Moreover, the functionality of the pre-miR switches for gene regulation through the interaction of the respective miRNA with its specific target sequence could be shown. Thus, this work describes the development of a RNA-based tool that is capable of robustly and reversibly controlling miRNA abundance. |
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URN: | urn:nbn:de:tuda-tuprints-61258 | ||||
Classification DDC: | 500 Science and mathematics > 500 Science 500 Science and mathematics > 570 Life sciences, biology |
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Divisions: | 10 Department of Biology 10 Department of Biology > Ribogenetics 10 Department of Biology > Synthetic Genetic Circuits (2020 renamed "Synthetic RNA biology) |
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Date Deposited: | 06 Apr 2017 08:08 | ||||
Last Modified: | 06 Apr 2017 08:08 | ||||
URI: | https://tuprints.ulb.tu-darmstadt.de/id/eprint/6125 | ||||
PPN: | 401483932 | ||||
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