Rational design of microRNA-responsive switch for programmable translational control in mammalian cells
Abstract Artificial RNA translation modulation usually relies on multiple components, such as RNA binding proteins (RBPs) or microRNAs (miRNAs) for off-switches and double-inverter cascades for on-switches. Recently, translational circular RNAs (circRNAs) were developed as promising alternatives for...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43065-w |
| _version_ | 1797630098322489344 |
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| author | Hui Ning Gan Liu Lei Li Qiang Liu Huiya Huang Zhen Xie |
| author_facet | Hui Ning Gan Liu Lei Li Qiang Liu Huiya Huang Zhen Xie |
| author_sort | Hui Ning |
| collection | DOAJ |
| description | Abstract Artificial RNA translation modulation usually relies on multiple components, such as RNA binding proteins (RBPs) or microRNAs (miRNAs) for off-switches and double-inverter cascades for on-switches. Recently, translational circular RNAs (circRNAs) were developed as promising alternatives for linear messenger RNAs (mRNAs). However, circRNAs still lack straightforward and programmable translation control strategies. Here, we rationally design a programmable miRNA-responsive internal ribosome entry site (IRES) translation activation and repression (PROMITAR) platform capable of implementing miRNA-based translation upregulation and downregulation in a single RNA construct. Based on the PROMITAR platform, we construct logic gates and cell-type classifier circRNAs and successfully identify desired mammalian cell types. We also demonstrate the potential therapeutic application of our platform for targeted cancer cell killing by encoding a cytotoxic protein in our engineered circRNAs. We expect our platform to expand the toolbox for RNA synthetic biology and provide an approach for potential biomedical applications in the future. |
| first_indexed | 2024-03-11T11:02:07Z |
| format | Article |
| id | doaj.art-53025df0a88d4fd0996a994735bd451d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T11:02:07Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-53025df0a88d4fd0996a994735bd451d2023-11-12T12:24:02ZengNature PortfolioNature Communications2041-17232023-11-0114111110.1038/s41467-023-43065-wRational design of microRNA-responsive switch for programmable translational control in mammalian cellsHui Ning0Gan Liu1Lei Li2Qiang Liu3Huiya Huang4Zhen Xie5MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Department of Automation, Beijing National Research Center for Information Science and Technology, Tsinghua UniversitySyngentech Inc., Zhongguancun Life Science Park, Changping DistrictMOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Department of Automation, Beijing National Research Center for Information Science and Technology, Tsinghua UniversitySyngentech Inc., Zhongguancun Life Science Park, Changping DistrictSyngentech Inc., Zhongguancun Life Science Park, Changping DistrictMOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Department of Automation, Beijing National Research Center for Information Science and Technology, Tsinghua UniversityAbstract Artificial RNA translation modulation usually relies on multiple components, such as RNA binding proteins (RBPs) or microRNAs (miRNAs) for off-switches and double-inverter cascades for on-switches. Recently, translational circular RNAs (circRNAs) were developed as promising alternatives for linear messenger RNAs (mRNAs). However, circRNAs still lack straightforward and programmable translation control strategies. Here, we rationally design a programmable miRNA-responsive internal ribosome entry site (IRES) translation activation and repression (PROMITAR) platform capable of implementing miRNA-based translation upregulation and downregulation in a single RNA construct. Based on the PROMITAR platform, we construct logic gates and cell-type classifier circRNAs and successfully identify desired mammalian cell types. We also demonstrate the potential therapeutic application of our platform for targeted cancer cell killing by encoding a cytotoxic protein in our engineered circRNAs. We expect our platform to expand the toolbox for RNA synthetic biology and provide an approach for potential biomedical applications in the future.https://doi.org/10.1038/s41467-023-43065-w |
| spellingShingle | Hui Ning Gan Liu Lei Li Qiang Liu Huiya Huang Zhen Xie Rational design of microRNA-responsive switch for programmable translational control in mammalian cells Nature Communications |
| title | Rational design of microRNA-responsive switch for programmable translational control in mammalian cells |
| title_full | Rational design of microRNA-responsive switch for programmable translational control in mammalian cells |
| title_fullStr | Rational design of microRNA-responsive switch for programmable translational control in mammalian cells |
| title_full_unstemmed | Rational design of microRNA-responsive switch for programmable translational control in mammalian cells |
| title_short | Rational design of microRNA-responsive switch for programmable translational control in mammalian cells |
| title_sort | rational design of microrna responsive switch for programmable translational control in mammalian cells |
| url | https://doi.org/10.1038/s41467-023-43065-w |
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