While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the current issue of Science, Nikolaus Rajewsky and his team at the Berlin Institute of Medical Systems Biology (BIMSB) of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), as well as other collaborators within the MDC and Charité, present data that — for the first time — link a circular RNA to brain function.

RNA is much more than the mundane messenger between DNA and the protein it encodes. Indeed, there are several different kinds of non-coding RNA molecules. They can be long non-coding RNAs (lncRNAs) or short regulatory RNAs (miRs); they can interfere with protein production (siRNAs) or help make it possible (tRNAs). In the past 20 years, scientists have discovered some two dozen RNA varieties that form intricate networks within the molecular microcosm. The most enigmatic among them are circRNAs, an unusual class of RNAs whose heads are connected to their tails to form a covalently closed ring. These structures had for decades been dismissed as a rare, exotic RNA species. In fact, the opposite is true. Current RNA-sequencing analyses have revealed that they are a large class of RNA, which is highly expressed in brain tissues.