An obvious advantage of a molecular computer over its electronic counterpart is its potential to operate within a biological environment, by responding to and acting on biological components. Win and Smolke previously created single input–single output RNA devices in the yeast Saccharomyces cerevisiae using three components: a sensor that detects the signal, a transmitter that conveys the signal and an actuator that mediates the intracellular response to the initiating signal. In their recent study, they extend this framework and construct various combinations of these basic modules, thus allowing them to create higher-order RNA devices that can act as Boolean logic gates and perform AND, OR, NAND (not-AND) and NOR (not-OR) operations.
The molecular modules used in the authors' system are RNA aptamers (the sensor) and ribozymes (the actuator), which are coupled by an RNA sequence (the transmitter). Aptamers are short RNA molecules that recognize and bind to specific target molecules. Ribozymes are short single-stranded molecules with enzymatic activity. Binding of an input molecule to the sensor causes a conformational shift in the sensor — this input molecule-bound conformation is increasingly favoured as the concentration of the input molecule increases; and this is translated to a change in ribozyme activity. Because the ribozyme is fused to the 3′ UTR of a target gene, changes in ribozyme activity modulate cleavage of the target transcript, thus altering the expression of that gene. The system can be designed so that binding of the input to the sensor either allows or blocks cleavage by the ribozyme. In their system, the authors used as inputs two small organic molecules, theophylline and tetracycline, and the output of the RNA device was GFP expression.
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