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Design principles for riboswitch function

Beisel, Chase L. and Smolke, Christina D. (2009) Design principles for riboswitch function. PLoS Computational Biology, 5 (4). Art. No. e1000363. ISSN 1553-734X. PMCID PMC2666153. https://resolver.caltech.edu/CaltechAUTHORS:20090722-113142433

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Abstract

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.pcbi.1000363DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666153/PubMed CentralArticle
ORCID:
AuthorORCID
Smolke, Christina D.0000-0002-5449-8495
Additional Information:© 2009 Beisel, Smolke. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received October 8, 2008; Accepted March 16, 2009; Published April 17, 2009. This work was supported by a grant from the Caltech Joseph Jacobs Institute for Molecular Engineering for Medicine to CDS and a National Defense Science and Engineering Graduate research fellowship from the Department of Defense to CLB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
Group:Jacobs Institute for Molecular Engineering for Medicine
Funders:
Funding AgencyGrant Number
Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
National Defense Science and Engineering Graduate (NDSEG) FellowshipUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC2666153
Record Number:CaltechAUTHORS:20090722-113142433
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20090722-113142433
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14635
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:31 Jul 2009 17:38
Last Modified:12 Feb 2020 20:25

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