Vogel, Marc ; Weigand, Julia E. ; Kluge, Britta ; Grez, Manuel ; Suess, Beatrix (2018)
A small, portable RNA device for the control of exon skipping in mammalian cells.
In: Nucleic acids research, 46 (8)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Splicing is an essential and highly regulated process in mammalian cells. We developed a synthetic riboswitch that efficiently controls alternative splicing of a cassette exon in response to the small molecule ligand tetracycline. The riboswitch was designed to control the accessibility of the 3' splice site by placing the latter inside the closing stem of a conformationally controlled tetracycline aptamer. In the presence of tetracycline, the cassette exon is skipped, whereas it is included in the ligand's absence. The design allows for an easy, context-independent integration of the regulatory device into any gene of interest. Portability of the device was shown through its functionality in four different systems: a synthetic minigene, a reporter gene and two endogenous genes. Furthermore, riboswitch functionality to control cellular signaling cascades was demonstrated by using it to specifically induce cell death through the conditionally controlled expression of CD20, which is a target in cancer therapy.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2018 |
| Autor(en): | Vogel, Marc ; Weigand, Julia E. ; Kluge, Britta ; Grez, Manuel ; Suess, Beatrix |
| Art des Eintrags: | Bibliographie |
| Titel: | A small, portable RNA device for the control of exon skipping in mammalian cells. |
| Sprache: | Englisch |
| Publikationsjahr: | 4 Mai 2018 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nucleic acids research |
| Jahrgang/Volume einer Zeitschrift: | 46 |
| (Heft-)Nummer: | 8 |
| Kurzbeschreibung (Abstract): | Splicing is an essential and highly regulated process in mammalian cells. We developed a synthetic riboswitch that efficiently controls alternative splicing of a cassette exon in response to the small molecule ligand tetracycline. The riboswitch was designed to control the accessibility of the 3' splice site by placing the latter inside the closing stem of a conformationally controlled tetracycline aptamer. In the presence of tetracycline, the cassette exon is skipped, whereas it is included in the ligand's absence. The design allows for an easy, context-independent integration of the regulatory device into any gene of interest. Portability of the device was shown through its functionality in four different systems: a synthetic minigene, a reporter gene and two endogenous genes. Furthermore, riboswitch functionality to control cellular signaling cascades was demonstrated by using it to specifically induce cell death through the conditionally controlled expression of CD20, which is a target in cancer therapy. |
| ID-Nummer: | pmid:29420816 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Synthetic Genetic Circuits (2020 umbenannt in "Synthetic RNA biology") 10 Fachbereich Biologie > RNA Biochemie |
| Hinterlegungsdatum: | 12 Feb 2018 13:38 |
| Letzte Änderung: | 06 Nov 2020 07:09 |
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