Engineering protein-protein devices for multilayered regulation of mRNA translation using orthogonal proteases in mammalian cells
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s41467-018-06825-7.pdf
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Author(s)
Cella, Federica
Wroblewska, Liliana
Weiss, Ron
Siciliano, Velia
Date Issued
October 2018
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Cella, Federica et al. “Engineering Protein-Protein Devices for Multilayered Regulation of mRNA Translation Using Orthogonal Proteases in Mammalian Cells.” Nature Communications 9, 1 (October 2018): 4392 © 2018 The Author(s)
Version
Final published version
Abstract
The development of RNA-encoded regulatory circuits relying on RNA-binding proteins (RBPs) has enhanced the applicability and prospects of post-transcriptional synthetic network for reprogramming cellular functions. However, the construction of RNA-encoded multilayer networks is still limited by the availability of composable and orthogonal regulatory devices. Here, we report on control of mRNA translation with newly engineered RBPs regulated by viral proteases in mammalian cells. By combining post-transcriptional and post-translational control, we expand the operational landscape of RNA-encoded genetic circuits with a set of regulatory devices including: i) RBP-protease, ii) protease-RBP, iii) protease–protease, iv) protein sensor protease-RBP, and v) miRNA-protease/RBP interactions. The rational design of protease-regulated proteins provides a diverse toolbox for synthetic circuit regulation that enhances multi-input information processing-actuation of cellular responses. Our approach enables design of artificial circuits that can reprogram cellular function with potential benefits as research tools and for future in vivo therapeutics and biotechnological applications.
MIT Department
Massachusetts Institute of Technology. Synthetic Biology Center
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41467-018-06825-7
