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Selecting small molecule DNA aptamers with significant conformational changes for constructing transcriptional switches and biosensors

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Abstract

Small molecule aptamers discovered by traditional selection methods usually lack conformational changes upon target binding. This limits the use of aptamers as molecular probes for small molecule detection and regulatory elements of genetic circuits. Here, we report a new method called capture and in vitro transcription-systematic evolution of ligands by exponential enrichment (CIVT-SELEX) to select DNA aptamers that can not only bind to small molecule ligands but also undergo significant conformational changes. Through this method, we select a structure-switching aptamer of uridine-5′-diphosphate (UDP). Taking advantage of its conformational changes, we first construct a UDP-responsive transcriptional switch by inserting the aptamer in a genetic circuit and demonstrate that it can respond to the addition of UDP and regulate the transcription of downstream genes. We also build a UDP aptamer-based biosensor that can be used for active glycosyltransferase screening. We believe this method can provide a universal platform for selecting small molecule aptamers with conformational changes and expand the use of aptamers in small molecule detection and genetic regulation.

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Acknowledgements

We would like to thank Dr. J. Yang, Dr. Y. Zheng, Dr. F. Li, Dr. M. Chen, and Dr. L. Chen for their helpful discussion and suggestions. This work was supported by the National Natural Science Foundation of China (32001037, 22176035), the National Key R&D Program of China (2020YFA0210800, 2018YFA0902600), the Natural Science Foundation of Fujian Province (2020J01491, 2020J05120), and Fuzhou University Research Fund (GXRC-20033).

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350108, China

    Shaobin Guo, Jingjing Lin, Lujie Lin, Yan Guo, Zipeng Xu, Xianai Shi & Huanghao Yang

  2. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China

    Wen Xu

  3. Key Laboratory for Analytical Science of Food Safety and Biology of Ministry of Education, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China

    Chunhua Lu, Lanlan Chen & Huanghao Yang

  4. Fujian Key Laboratory of Medical Instrument and Pharmaceutical Technology, Fuzhou University, Fuzhou, 350108, China

    Xianai Shi

Authors
  1. Shaobin Guo
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  2. Jingjing Lin
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  3. Lujie Lin
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  4. Wen Xu
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  5. Yan Guo
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  6. Zipeng Xu
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  7. Chunhua Lu
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  8. Xianai Shi
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  9. Lanlan Chen
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  10. Huanghao Yang
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Corresponding authors

Correspondence to Lanlan Chen or Huanghao Yang.

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The authors declare no conflict of interest.

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The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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11426_2022_1540_MOESM1_ESM.pdf

Selecting Small Molecule DNA Aptamers with Significant Conformational Changes for Constructing Transcriptional Switches and Biosensors

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Guo, S., Lin, J., Lin, L. et al. Selecting small molecule DNA aptamers with significant conformational changes for constructing transcriptional switches and biosensors. Sci. China Chem. 66, 1529–1536 (2023). https://doi.org/10.1007/s11426-022-1540-y

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  • DOI: https://doi.org/10.1007/s11426-022-1540-y

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