Rodrigo, Guillermo, Prakash, Satya, Shen, Shensi, Majer, Eszter, Daròs, José-Antonio and Jaramillo, Alfonso (2017) Model-based design of RNA hybridization networks implemented in living cells. Nucleic Acids Research, 45 (16). pp. 9797-9808. doi:10.1093/nar/gkx698 ISSN 0305-1048.

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Abstract

Synthetic gene circuits allow the behavior of living cells to be reprogrammed, and non-coding small RNAs (sRNAs) are increasingly being used as programmable regulators of gene expression. However, sRNAs (natural or synthetic) are generally used to regulate single target genes, while complex dynamic behaviors would require networks of sRNAs regulating each other. Here, we report a strategy for implementing such networks that exploits hybridization reactions carried out exclusively by multifaceted sRNAs that are both targets of and triggers for other sRNAs. These networks are ultimately coupled to the control of gene expression. We relied on a thermodynamic model of the different stable conformational states underlying this system at the nucleotide level. To test our model, we designed five different RNA hybridization networks with a linear architecture, and we implemented them in Escherichia coli. We validated the network architecture at the molecular level by native polyacrylamide gel electrophoresis, as well as the network function at the bacterial population and single-cell levels with a fluorescent reporter. Our results suggest that it is possible to engineer complex cellular programs based on RNA from first principles. Because these networks are mainly based on physical interactions, our designs could be expanded to other organisms as portable regulatory resources or to implement biological computations.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre
Library of Congress Subject Headings (LCSH):	Non-coding RNA, Synthetic biology, Genetic regulation, Escherichia coli -- Genetics
Journal or Publication Title:	Nucleic Acids Research
Publisher:	Oxford University Press
ISSN:	0305-1048
Official Date:	19 September 2017
Dates:	Date Event 19 September 2017 Published 1 August 2017 Available 27 July 2017 Accepted 17 May 2017 Submitted
Volume:	45
Number:	16
Page Range:	pp. 9797-9808
DOI:	10.1093/nar/gkx698
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	9 August 2018
Date of first compliant Open Access:	9 August 2018
Funder:	Seventh Framework Programme (European Commission) (FP7), Horizon 2020 (European Commission) (H2020), Engineering and Physical Sciences Research Council (EPSRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University of Warwick. School of Life Sciences
Grant number:	610730 (FP7), 613745 (FP7), 642738 (H2020), BB/M017982/1 (BBSRC)

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