Putting RNA to work: Translating RNA fundamentals into biotechnological engineering practice

Synthetic biology, in close concert with systems biology, is revolutionizing the field of metabolic engineering by providing novel tools and technologies to rationally, in a standardized way, reroute metabolism with a view to optimally converting renewable resources into a broad range of bio-products, bio-materials and bio-energy. Increasingly, these novel synthetic biology tools are exploiting the extensive programmable nature of RNA, vis-à-vis DNA- and protein-based devices, to rationally design standardized, composable, and orthogonal parts, which can be scaled and tuned promptly and at will. This review gives an extensive overview of the recently developed parts and tools for i) modulating gene expression ii) building genetic circuits iii) detecting molecules, iv) reporting cellular processes and v) building RNA nanostructures. These parts and tools are becoming necessary armamentarium for contemporary metabolic engineering. Furthermore, the design criteria, technological challenges, and recent metabolic engineering success stories of the use of RNA devices are highlighted. Finally, the future trends in transforming metabolism through RNA engineering are critically evaluated and summarized.