In the past funding period, we have made significant progress in combining methods of photoregulation with the control of RNA function. In the new funding period, we want to combine these findings and push their application to new limits in diverse fields – together with quite a number of projects of this CRC: In a continuing long-term project between the Heckel group and the Schwalbe group (A1), the Suess group (A2) and the Wachtveitl group (A7) we will continue to develop a riboswitch against a photoswitchable small molecule. Our efforts have so far resulted in several aptamers, which bind with good affinity (600 nM) to the trans photoisomers of a chloramphenicol-derivatized azobenzene (“azoCm”) while no interaction could be detected to the cis photoisomer. With the new capture SELEX approaches established in the Suess group (A2), we will refine our search for photoswitchable riboswitches. In a second set of projects, we will build on the successful regulation of miR-92a in the skin of living mice with light but we now want to target regulatory RNA deeper in living organisms. This requires photochemical strategies which are fine-tuned to certain wavelength windows. With the collaborative potential of this CRC we want to target the heart and the thymus of mice and even plants. In all of these cases we will provide light-regulatable antimiRs as well as (pre-)microRNA mimics. Also, based on findings of the previous funding period, we want to perfect the photoswitching of hybridization of RNA and the regulation of the formation of RNA G-quadruplexes.