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Modulating myoblast differentiation with RNA-based controllers

Tunable genetic controllers play a critical role in the engineering of biological systems that respond to environmental and cellular signals. RNA devices, a class of engineered RNA-based controllers, enable tunable gene expression control of target genes in response to molecular effectors. RNA devic...

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Detalles Bibliográficos
Autores principales: Dykstra, Peter B., Rando, Thomas A., Smolke, Christina D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9514614/
https://www.ncbi.nlm.nih.gov/pubmed/36166456
http://dx.doi.org/10.1371/journal.pone.0275298
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author Dykstra, Peter B.
Rando, Thomas A.
Smolke, Christina D.
author_facet Dykstra, Peter B.
Rando, Thomas A.
Smolke, Christina D.
author_sort Dykstra, Peter B.
collection PubMed
description Tunable genetic controllers play a critical role in the engineering of biological systems that respond to environmental and cellular signals. RNA devices, a class of engineered RNA-based controllers, enable tunable gene expression control of target genes in response to molecular effectors. RNA devices have been demonstrated in a number of systems showing proof-of-concept of applying ligand-responsive control over therapeutic activities, including regulation of cell fate decisions such as T cell proliferation and apoptosis. Here, we describe the application of a theophylline-responsive RNA device in a muscle progenitor cell system to control myogenic differentiation. Ribozyme-based RNA switches responsive to theophylline control fluorescent reporter expression in C2C12 myoblasts in a ligand dependent manner. HRAS and JAK1, both anti-differentiation proteins, were incorporated into RNA devices. Finally, we demonstrate that the regulation of HRAS expression via theophylline-responsive RNA devices results in the modulation of myoblast differentiation in a theophylline-dependent manner. Our work highlights the potential for RNA devices to exert drug-responsive, tunable control over cell fate decisions with applications in stem cell therapy and basic stem cell biology research.
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spelling pubmed-95146142022-09-28 Modulating myoblast differentiation with RNA-based controllers Dykstra, Peter B. Rando, Thomas A. Smolke, Christina D. PLoS One Research Article Tunable genetic controllers play a critical role in the engineering of biological systems that respond to environmental and cellular signals. RNA devices, a class of engineered RNA-based controllers, enable tunable gene expression control of target genes in response to molecular effectors. RNA devices have been demonstrated in a number of systems showing proof-of-concept of applying ligand-responsive control over therapeutic activities, including regulation of cell fate decisions such as T cell proliferation and apoptosis. Here, we describe the application of a theophylline-responsive RNA device in a muscle progenitor cell system to control myogenic differentiation. Ribozyme-based RNA switches responsive to theophylline control fluorescent reporter expression in C2C12 myoblasts in a ligand dependent manner. HRAS and JAK1, both anti-differentiation proteins, were incorporated into RNA devices. Finally, we demonstrate that the regulation of HRAS expression via theophylline-responsive RNA devices results in the modulation of myoblast differentiation in a theophylline-dependent manner. Our work highlights the potential for RNA devices to exert drug-responsive, tunable control over cell fate decisions with applications in stem cell therapy and basic stem cell biology research. Public Library of Science 2022-09-27 /pmc/articles/PMC9514614/ /pubmed/36166456 http://dx.doi.org/10.1371/journal.pone.0275298 Text en © 2022 Dykstra et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dykstra, Peter B.
Rando, Thomas A.
Smolke, Christina D.
Modulating myoblast differentiation with RNA-based controllers
title Modulating myoblast differentiation with RNA-based controllers
title_full Modulating myoblast differentiation with RNA-based controllers
title_fullStr Modulating myoblast differentiation with RNA-based controllers
title_full_unstemmed Modulating myoblast differentiation with RNA-based controllers
title_short Modulating myoblast differentiation with RNA-based controllers
title_sort modulating myoblast differentiation with rna-based controllers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9514614/
https://www.ncbi.nlm.nih.gov/pubmed/36166456
http://dx.doi.org/10.1371/journal.pone.0275298
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