Groher, Florian ; Bofill-Bosch, Cristina ; Schneider, Christopher ; Braun, Johannes ; Jager, Sven ; Geißler, Katharina ; Hamacher, Kay ; Suess, Beatrix (2018)
Riboswitching with ciprofloxacin-development and characterization of a novel RNA regulator.
In: Nucleic acids research, 46 (4)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswitch by in vitro selection and next-generation sequencing-guided cellular screening. The riboswitch recognizes the small molecule drug ciprofloxacin with a KD in the low nanomolar range and adopts a pseudoknot fold stabilized by ligand binding. It efficiently interferes with gene expression both in lower and higher eukaryotes. By controlling an auxotrophy marker and a resistance gene, respectively, we demonstrate efficient, scalable and programmable control of cellular survival in yeast. The applied strategy for the development of the ciprofloxacin riboswitch is easily transferrable to any small molecule target of choice and will thus broaden the spectrum of RNA regulators considerably.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2018 |
| Autor(en): | Groher, Florian ; Bofill-Bosch, Cristina ; Schneider, Christopher ; Braun, Johannes ; Jager, Sven ; Geißler, Katharina ; Hamacher, Kay ; Suess, Beatrix |
| Art des Eintrags: | Bibliographie |
| Titel: | Riboswitching with ciprofloxacin-development and characterization of a novel RNA regulator. |
| Sprache: | Englisch |
| Publikationsjahr: | Februar 2018 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nucleic acids research |
| Jahrgang/Volume einer Zeitschrift: | 46 |
| (Heft-)Nummer: | 4 |
| Kurzbeschreibung (Abstract): | RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswitch by in vitro selection and next-generation sequencing-guided cellular screening. The riboswitch recognizes the small molecule drug ciprofloxacin with a KD in the low nanomolar range and adopts a pseudoknot fold stabilized by ligand binding. It efficiently interferes with gene expression both in lower and higher eukaryotes. By controlling an auxotrophy marker and a resistance gene, respectively, we demonstrate efficient, scalable and programmable control of cellular survival in yeast. The applied strategy for the development of the ciprofloxacin riboswitch is easily transferrable to any small molecule target of choice and will thus broaden the spectrum of RNA regulators considerably. |
| ID-Nummer: | pmid:29346617 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Computational Biology and Simulation 10 Fachbereich Biologie > Synthetic Genetic Circuits (2020 umbenannt in "Synthetic RNA biology") |
| Hinterlegungsdatum: | 23 Jan 2018 07:43 |
| Letzte Änderung: | 06 Sep 2018 08:21 |
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