Mapping the Operational Landscape of MicroRNAs in Synthetic Gene Circuits.

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Mapping the Operational Landscape of MicroRNAs in Synthetic Gene Circuits.

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Title: Mapping the Operational Landscape of MicroRNAs in Synthetic Gene Circuits.
Author(s):
Quarton, Tyler;
Ehrhardt, Kristina;
Lee, James;
Kannan, Srijaa;
Li, Yi;
Ma, Lan;
Bleris, Leonidas
Date Created: 2018-10-22
Format: Text
Item Type: article
Keywords: MicroRNAs
Renal cells
Gene Expression
Abstract: MicroRNAs are a class of short, noncoding RNAs that are ubiquitous modulators of gene expression, with roles in development, homeostasis, and disease. Engineered microRNAs are now frequently used as regulatory modules in synthetic biology. Moreover, synthetic gene circuits equipped with engineered microRNA targets with perfect complementarity to endogenous microRNAs establish an interface with the endogenous milieu at the single-cell level. The function of engineered microRNAs and sensor systems is typically optimized through extensive trial-and-error. Here, using a combination of synthetic biology experimentation in human embryonic kidney cells and quantitative analysis, we investigate the relationship between input genetic template abundance, microRNA concentration, and output under microRNA control. We provide a framework that employs the complete operational landscape of a synthetic gene circuit and enables the stepwise development of mathematical models. We derive a phenomenological model that recapitulates experimentally observed nonlinearities and contains features that provide insight into the microRNA function at various abundances. Our work facilitates the characterization and engineering of multi-component genetic circuits and specifically points to new insights on the operation of microRNAs as mediators of endogenous information and regulators of gene expression in synthetic biology.
Publisher: Nature Partner Journals
ISSN: 2056-7189
Link to Related Resource: https://dx.doi.org/10.1038/s41540-017-0043-y
Persistent Link: http://hdl.handle.net/10735.1/6209
Bibliographic Citation: Quarton, Tyler, Kristina Ehrhardt, James Lee, Srijaa Kannan, et al. 2018. "Mapping the operational landscape of microRNAs in synthetic gene circuits.." Npj Systems Biology And Applications 4: 6.
Terms of Use: CC BY 4.0 (Attribution)
©2018 The Authors.
Sponsors: US National Science Foundation (NSF) CAREER grant 1351354, NSF 1361355.

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CC BY 4.0 (Attribution) Except where otherwise noted, this item's license is described as CC BY 4.0 (Attribution)