189Synthetic Biology: Parts, Devices and Applications, First Edition. Edited by Christina Smolke.
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA.
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Through control of messenger RNA stability, bacteria are able to process infor-
mation, respond to changing conditions, and maintain homeostasis. Many of the
naturally occurring mechanisms for transcript stability control (TSC) have been
elucidated, and a number of studies have leveraged this understanding to dem-
onstrate that transcript stability can be engineered to control static and dynamic
gene expression. Collectively, that body of work represents a foundation for
developing new forward-engineering approaches that harness mechanistic
understanding to build predictive computational models to guide the develop-
ment of large-scale genetic devices based on TSC and other means. Further
increasing our understanding of RNA degradation pathways and mechanisms
will also improve the ability to anticipate how undesired variations in transcript
stability may confound device output goals and frustrate engineering efforts.
Here, we discuss the current state of the art and identify routes for using TSC to
design increasingly large and complex synthetic biological systems.
10.1 An Introduction to Transcript Control
10.1.1 Why Consider Transcript Control?
In naturally occurring biological systems, RNA-based genetic control mecha-
nisms play crucial roles in regulating cellular functions. Genome-wide studies of
bacterial transcript half-lives [1, 2] have underscored the importance that con-
trol over transcript stability plays in enabling bacteria to process information,
respond to changing cellular and environmental conditions, and, ultimately,
maintain homeostasis. Bacterial transcripts are known to persist for times that
vary in scale over orders of magnitude, from only a few seconds to an hour, or
more. Nature uses several mechanisms to control transcript persistence [3–6],
and experimental evidence has shown that these mechanisms can be engineered
[7–10], providing a route to programming static and dynamic gene expression
[11]. Developing technologies for designing variations in transcript stability
Programming Gene Expression by Engineering
10.2.1 Transcript Stability Control as a “Tuning Knob”
Jason T. Stevens and James M. Carothers
University of Washington, Center for Synthetic Biology, Molecular Engineering and Sciences Institute, Departments
of Chemical Engineering and Bioengineering, 4000 15th Ave NE, Seattle, WA 98195-1654, USA