TY - JOUR T1 - Computational design of Small Transcription Activating RNAs (STARs) for versatile and dynamic gene regulation JF - bioRxiv DO - 10.1101/169391 SP - 169391 AU - James Chappell AU - Alexandra Westbrook AU - Matthew Verosloff AU - Julius B. Lucks Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/28/169391.abstract N2 - A longstanding goal of synthetic biology has been the programmable control of cellular functions. Central to this goal is the creation of versatile regulatory toolsets that allow for programmable control of gene expression. Of the many regulatory molecules available, RNA regulators offer the intriguing possibility of de novo design – allowing for the bottom-up molecular-level design of genetic control systems. Here we present a computational design approach for the creation of a bacterial regulator called Small Transcription Activating RNAs (STARs) and create a library of high-performing and orthogonal STARs that achieve up to ∼9000-fold gene activation. We then demonstrate the versatility of RNA-based transcription control by showing the broad utility of STARs – from acting synergistically with existing constitutive and inducible regulators, to reprogramming cellular phenotypes and controlling multigene metabolic pathway expression. Finally, we combine these new STARs with themselves and CRISPRi transcriptional repressors to deliver new types of RNA-based genetic circuitry that allow for sophisticated and temporal control of gene expression. ER -