Synthetic RNA switches as a tool for temporal and spatial control over gene expression

Abstract

The engineering of biological systems offers significant promise for advances in areas including health and medicine, chemical synthesis, energy production, and environmental sustainability. Realizing this potential requires tools that enable design of sophisticated genetic systems. The functional diversity of RNA makes it an attractive and versatile substrate for programming sensing, information processing, computation, and control functions. Recent advances in the design of synthetic RNA switches capable of detecting and responding to molecular and environmental signals enable dynamic modulation of gene expression through diverse mechanisms, including transcription, splicing, stability, RNA interference, and translation. Furthermore, implementation of these switches in genetic circuits highlights the potential for building synthetic cell systems targeted to applications in environmental remediation and next-generation therapeutics and diagnostics.

Modular optimization of multi-gene pathways for fumarate production

“…Finally, reducing the production of byproducts by sRNA switches enabled further improvement in fumarate production up to 33.13 g/L in TGFA091-16. This result was probably due to the fact that synthetic RNA switches enable dynamic modulation of gene expression through diverse mechanisms, including transcription, splicing, stability, RNA interference, and translation (Chang et al, 2012).…”

Controlling mRNA stability and translation with the CRISPR endoribonuclease Csy4

“…Artificial control of gene expression, on the other hand, requires the development of small molecule, protein or RNAbased tools and is essential for advancing synthetic biology and gene therapies. Post-transcriptional regulation of gene expression has been achieved by engineering RNA, for instance by using riboswitches that can not only be exploited to gain insight into endogenous RNA processing mechanisms, but also as programmable elements for building gene circuits (Chang et al 2012). Another promising platform for developing RNA regulatory tools is the Pumilio/ fem-3 binding factor or PUF proteins that recognize singlestranded RNA in a sequence-specific fashion (Wang et al 2013).…”

Applications and advances of metabolite biosensors for metabolic engineering

“…4b), a strategy predominantly used by prokaryotes to regulate translation initiation (Chang et al, 2012). Based on this mechanism, synthetic riboswitches have been engineered to sense a series of metabolites, including theophylline (Topp et al, 2010), ammeline (Dixon et al, 2010), and thiamine pyrophosphate (Muranaka et al, 2009).…”