Small hairpin RNA as a small molecule sensor

Mol Syst Biol. 4: 227Life has perfected the art of connecting the myriad molecular components in a live cell through regulatory links, transforming a cell from a mere protein shake into the most complex physical system known to man. Research in synthetic biology has strived, among other things, to recreate this complexity to a modest degree. This requires building new regulatory links and networks according to pre‐designed blueprints to generate new biological functions, augment cells with new capabilities and perhaps fix malfunctions in the cell's own programs. As of today, we are still far from being able to take an abstract specification of a network or function and build its working implementation. In a series of reports, including the recent article published in Molecular Systems Biology by Beisel et al (2008), researchers have made a significant step towards this goal. They describe rationally designed molecular switches that can, in principle, use an arbitrary small molecule to affect the amount of an arbitrary messenger RNA (mRNA) via the RNA interference (RNAi) pathway. These switches significantly expand the repertoire of tools available to synthetic biologists, and they will undoubtedly benefit basic biological studies and biomedicine.For about a decade now, researchers in synthetic biology have been co‐opting a variety of regulatory modalities into the ‘biological parts’ toolbox (Baker et al , 2006). Ideally, we want these parts to be amenable to rational design, and be scalable and programmable. The former will let us establish regulatory links at will, such as ‘high concentration of protein A should activate protein B’. The latter will enable multiplying these links and defining their mutual relation. For example, we may require that protein A, microRNA B and small molecule …