Synthetic devices that target endogenous gene regulation can be used to engineer genetic systems to control cellular behavior.The constructing of regulatory circuits has been limited by the inabilities of cellular genes to interface with exogenous signals.Here, we describe a serial of RNA controllers that overcome this limitation by regulating endogenous gene expression in response to any ligand of choice.We show that the RNA controllers can efficiently repress translation of genes of interest in human cells.Any ligands not associated with gene regulation can be directed to inhibit targeted gene translation through the designed RNA controllers.The effective RNA controllers can be included in the synthetic biology toolbox that allows for construction of novel signaling pathways and regulatory loops.