Biomolecular engineering of intracellular switches in eukaryotes

<p>Tools to selectively and reversibly control gene expression are useful to study and model cellular functions. When optimized, these cellular<br>switches can turn a protein’s function “on” and “off” based on cues designated by the researcher. These cues include small molecules, drugs,<br>hormones, and even temperature variations. Here we review three distinct areas in gene expression that are commonly targeted when designing<br>cellular switches. Transcriptional switches target gene expression at the level of mRNA polymerization, with examples including the tetracycline<br>gene induction system as well as nuclear receptors. Translational switches target the process of turning the mRNA signal into protein, with examples<br>including riboswitches and RNA interference. Post-translational switches control how proteins interact with one another to attenuate or<br>relay signals. Examples of post-translational modification include dimerization and intein splicing. In general, the delay times between switch<br>and effect decreases from transcription to translation to post-translation; furthermore, the fastest switches may offer the most elegant opportunities<br>to influence and study cell behavior. We discuss the pros and cons of these strategies, which directly influence their usefulness to study and<br>implement drug targeting at the tissue and cellular level.</p> <p>