Aptamer-Mediated Control of Polyadenylation for Gene Expression Regulation in Mammalian Cells

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Zusammenfassung

Small aptamer-based regulatory devices can be designed to control a range of RNA-dependent cellular processes and emerged as promising tools for fine-tuning gene expression in synthetic biology. Here, we design a conceptually new riboswitch device that allows for the conditional regulation of polyadenylation. By making use of ligand-induced sequence occlusion, the system efficiently controls the accessibility of the eukaryotic polyadenylation signal. Undesirable 3'-extended read-through products are counteracted by the downstream insertion of a microRNA target site. We demonstrate the modularity of the system with regard to sensor aptamers and polyadenylation signals used and combine the newly designed riboswitch with well-known aptazymes to yield superior composite systems. In addition, we show that the switches can be used to control alternative polyadenylation. The presented genetic switches require very little coding space and can be easily optimized by rational adjustments of the thermodynamic stability. The polyadenylation riboswitch extends the repertoire of RNA-based regulators and opens new possibilities for the generation of complex synthetic circuits.

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540 Chemie
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synthetic riboswitch, conditional gene expression, polyadenylation, guanine aptamer, tetracycline aptamer, miRNA
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ISO 690SPÖRING, Maike, Ronja BONEBERG, Jörg S. HARTIG, 2020. Aptamer-Mediated Control of Polyadenylation for Gene Expression Regulation in Mammalian Cells. In: ACS Synthetic Biology. American Chemical Society (ACS). 2020, 9(11), pp. 3008-3018. eISSN 2161-5063. Available under: doi: 10.1021/acssynbio.0c00222
BibTex
@article{Sporing2020-11-20Aptam-51988,
  year={2020},
  doi={10.1021/acssynbio.0c00222},
  title={Aptamer-Mediated Control of Polyadenylation for Gene Expression Regulation in Mammalian Cells},
  number={11},
  volume={9},
  journal={ACS Synthetic Biology},
  pages={3008--3018},
  author={Spöring, Maike and Boneberg, Ronja and Hartig, Jörg S.}
}
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