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Repurposing the mam...
Repurposing the mammalian RNA-binding protein Musashi-1 as an allosteric translation repressor in bacteria
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- Dolcemascolo, Roswitha (författare)
- Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain.;Univ Politecn Valencia, Dept Biotechnol, Valencia, Spain.
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- Heras-Hernandez, Maria (författare)
- Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain.
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- Goiriz, Lucas (författare)
- Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain.;Univ Politecn Valencia, Dept Appl Math, Valencia, Spain.
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- Montagud-Martinez, Roser (författare)
- Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain.;Univ Politecn Valencia, Dept Biotechnol, Valencia, Spain.
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- Requena-Menendez, Alejandro (författare)
- Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain.
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- Ruiz, Raul (författare)
- Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain.
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- Perez-Rafols, Anna (författare)
- Giotto Biotech SRL, Sesto Fiorentino, Italy.;Univ Florence, Magnet Resonance Ctr CERM, Dept Chem Ugo Schiff, Consorzio Interuniv Risonanze Magnet Metalloprotei, Sesto Fiorentino, Italy.
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- Higuera-Rodriguez, R. Anahi (författare)
- Dynam Biosensors GmbH, Planegg, Germany.;Tech Univ Munich, Dept Phys, Garching, Germany.
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- Pérez-Ropero, Guillermo (författare)
- Uppsala universitet,Biokemi,Ridgeview Instruments AB, Uppsala, Sweden.
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- Vranken, Wim F. (författare)
- Vrije Univ Brussel, Struct Biol Brussels, Brussels, Belgium.;Vrije Univ Brussel, Univ Libre Bruxelles, Interuniv Inst Bioinformat Brussels, Brussels, Belgium.
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- Martelli, Tommaso (författare)
- Giotto Biotech SRL, Sesto Fiorentino, Italy.
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- Kaiser, Wolfgang (författare)
- Dynam Biosensors GmbH, Planegg, Germany.
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- Buijs, Jos (författare)
- Uppsala universitet,Cancerprecisionsmedicin,Ridgeview Instruments AB, Uppsala, Sweden.
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- Rodrigo, Guillermo (författare)
- Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain.
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Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain;Univ Politecn Valencia, Dept Biotechnol, Valencia, Spain. Univ Valencia, CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain. (creator_code:org_t)
- eLife Sciences Publications Ltd, 2024
- 2024
- Engelska.
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
- Relaterad länk:
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https://doi.org/10.7...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.7...
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Abstract
Ämnesord
Stäng
- The RNA recognition motif (RRM) is the most common RNA-binding protein domain identified in nature. However, RRM-containing proteins are only prevalent in eukaryotic phyla, in which they play central regulatory roles. Here, we engineered an orthogonal post-transcriptional control system of gene expression in the bacterium Escherichia coli with the mammalian RNA-binding protein Musashi-1, which is a stem cell marker with neurodevelopmental role that contains two canonical RRMs. In the circuit, Musashi-1 is regulated transcriptionally and works as an allosteric translation repressor thanks to a specific interaction with the N-terminal coding region of a messenger RNA and its structural plasticity to respond to fatty acids. We fully characterized the genetic system at the population and single-cell levels showing a significant fold change in reporter expression, and the underlying molecular mechanism by assessing the in vitro binding kinetics and in vivo functionality of a series of RNA mutants. The dynamic response of the system was well recapitulated by a bottom-up mathematical model. Moreover, we applied the post-transcriptional mechanism engineered with Musashi-1 to specifically regulate a gene within an operon, implement combinatorial regulation, and reduce protein expression noise. This work illustrates how RRM-based regulation can be adapted to simple organisms, thereby adding a new regulatory layer in prokaryotes for translation control.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- binding kinetics
- dynamic systems and modelling
- genetic circuits
- post-transcriptional regulation
- RNA recognition motif
- synthetic biology
- E. coli
- Mouse
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Dolcemascolo, Ro ...
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Heras-Hernandez, ...
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Goiriz, Lucas
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Montagud-Martine ...
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Requena-Menendez ...
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Ruiz, Raul
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Perez-Rafols, An ...
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Higuera-Rodrigue ...
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Pérez-Ropero, Gu ...
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Vranken, Wim F.
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Martelli, Tommas ...
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Kaiser, Wolfgang
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Buijs, Jos
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Rodrigo, Guiller ...
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