Small aptamer-based regulatory devices can be designed to control
a range of RNA-dependent cellular processes and emerged as promising
tools for fine-tuning gene expression in synthetic biology. Here,
we design a conceptually new riboswitch device that allows for the
conditional regulation of polyadenylation. By making use of ligand-induced
sequence occlusion, the system efficiently controls the accessibility
of the eukaryotic polyadenylation signal. Undesirable 3′-extended
read-through products are counteracted by the downstream insertion
of a microRNA target site. We demonstrate the modularity of the system
with regard to sensor aptamers and polyadenylation signals used and
combine the newly designed riboswitch with well-known aptazymes to
yield superior composite systems. In addition, we show that the switches
can be used to control alternative polyadenylation. The presented
genetic switches require very little coding space and can be easily
optimized by rational adjustments of the thermodynamic stability.
The polyadenylation riboswitch extends the repertoire of RNA-based
regulators and opens new possibilities for the generation of complex
synthetic circuits.
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