Atanasov, Janina (2017)
Design and implementation of a synthetic pre-miR switch for controlling miRNA biogenesis in mammals.
Technische Universität Darmstadt
Dissertation, Erstveröffentlichung
Kurzbeschreibung (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.
Typ des Eintrags: | Dissertation | ||||
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Erschienen: | 2017 | ||||
Autor(en): | Atanasov, Janina | ||||
Art des Eintrags: | Erstveröffentlichung | ||||
Titel: | Design and implementation of a synthetic pre-miR switch for controlling miRNA biogenesis in mammals | ||||
Sprache: | Englisch | ||||
Referenten: | Süß, Prof. Dr. Beatrix ; Löwer, Prof. Dr. Alexander | ||||
Publikationsjahr: | 30 März 2017 | ||||
Ort: | Darmstadt | ||||
Datum der mündlichen Prüfung: | 28 März 2017 | ||||
URL / URN: | http://tuprints.ulb.tu-darmstadt.de/6125 | ||||
Kurzbeschreibung (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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Alternatives oder übersetztes Abstract: |
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URN: | urn:nbn:de:tuda-tuprints-61258 | ||||
Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
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Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Regulatorische RNAs und Ribozyme 10 Fachbereich Biologie > Synthetic Genetic Circuits (2020 umbenannt in "Synthetic RNA biology") |
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Hinterlegungsdatum: | 09 Apr 2017 19:55 | ||||
Letzte Änderung: | 09 Apr 2017 19:55 | ||||
PPN: | |||||
Referenten: | Süß, Prof. Dr. Beatrix ; Löwer, Prof. Dr. Alexander | ||||
Datum der mündlichen Prüfung / Verteidigung / mdl. Prüfung: | 28 März 2017 | ||||
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