Sangam: A Confluence of Knowledge Streams

Engineering protein-protein devices for multilayered regulation of mRNA translation using orthogonal proteases in mammalian cells

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dc.contributor Massachusetts Institute of Technology. Synthetic Biology Center
dc.contributor Massachusetts Institute of Technology. Department of Biological Engineering
dc.creator Cella, Federica
dc.creator Wroblewska, Liliana
dc.creator Weiss, Ron
dc.creator Siciliano, Velia
dc.date 2020-11-13T22:14:51Z
dc.date 2020-11-13T22:14:51Z
dc.date 2018-10
dc.date 2018-07
dc.date 2019-03-04T13:30:56Z
dc.date.accessioned 2023-03-01T18:09:42Z
dc.date.available 2023-03-01T18:09:42Z
dc.identifier 2041-1723
dc.identifier https://hdl.handle.net/1721.1/128482
dc.identifier 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)
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/278982
dc.description 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.
dc.description NIH (P50-GM098792)
dc.format application/pdf
dc.publisher Springer Science and Business Media LLC
dc.relation http://dx.doi.org/10.1038/s41467-018-06825-7
dc.relation Nature Communications
dc.rights Creative Commons Attribution 4.0 International license
dc.rights https://creativecommons.org/licenses/by/4.0/
dc.source Nature
dc.title Engineering protein-protein devices for multilayered regulation of mRNA translation using orthogonal proteases in mammalian cells
dc.type Article
dc.type http://purl.org/eprint/type/JournalArticle


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