ArticleACS synthetic biology2012
Feedback control of protein expression in mammalian cells by tunable synthetic translational inhibition.
Article in ACS synthetic biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 100 citations in OpenAlex.
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- A genetic mammalian proportional-integral feedback control circuit for robust and precise gene regulation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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- PERSIST platform provides programmable RNA regulation using CRISPR endoRNases.Nature communications · 2022Article
- A hierarchy of biomolecular proportional-integral-derivative feedback controllers for robust perfect adaptation and dynamic performance.Nature communications · 2022Article
- Directed evolution of orthogonal RNA-RBP pairs through library-vs-library in vitro selection.Nucleic acids research · 2022Article
- Mechanobiology of immune cells: Messengers, receivers and followers in leishmaniasis aiding synthetic devices.Current research in immunology · 2022Review
- Oral antibiotics relieve allergic asthma in post-weaning miceFrontiers in immunology · 2022Article
- A synthetic distributed genetic multi-bit counter.iScience · 2021Article
- Protein-Based Systems for Translational Regulation of Synthetic mRNAs in Mammalian Cells.Life (Basel, Switzerland) · 2021Review
- Context-aware synthetic biology by controller design: Engineering the mammalian cell.Cell systems · 2021Review
- Overcoming the design, build, test bottleneck for synthesis of nonrepetitive protein-RNA cassettes.Nature communications · 2021Article
- Using sliding mode observers to estimateIET systems biology · 2020Article
- The Molecular Floodgates of Stress-Induced Senescence Reveal Translation, Signalling and Protein Activity Central to the Post-Mortem Proteome.International journal of molecular sciences · 2020Article
- Caliciviral protein-based artificial translational activator for mammalian gene circuits with RNA-only delivery.Nature communications · 2020Article
- Auto-regulatory feedback by RNA-binding proteins.Journal of molecular cell biology · 2019Review
- Adaptive information processing of network modules to dynamic and spatial stimuli.BMC systems biology · 2019Article
- Synthetic switch to minimize CRISPR off-target effects by self-restricting Cas9 transcription and translation.Nucleic acids research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Feedback regulation plays a crucial role in dynamic gene expression in nature, but synthetic translational feedback systems have yet to be demonstrated. Here we use an RNA/protein interaction-based synthetic translational switch to create a feedback system that tightly controls the expression of proteins of interest in mammalian cells. Feedback is mediated by modified ribosomal L7Ae proteins, which bind a set of RNA motifs with a range of affinities. We designed these motifs into L7Ae-encoding mRNA. Newly translated L7Ae binds its own mRNA, inhibiting further translation. This inhibition tightly feedback-regulates the concentration of L7Ae and any fusion partner of interest. A mathematical model predicts system behavior as a function of RNA/protein affinity. We further demonstrate that the L7Ae protein can simultaneously and tunably regulate the expression of multiple proteins of interest by binding RNA control motifs built into each mRNA, allowing control over the coordinated expression of protein networks.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.