Pentatricopeptide repeat (PPR) proteins control diverse aspects of RNA metabolism in eukaryotic cells. Although recent computational and structural studies have provided insights into RNA recognition by PPR proteins, their highly insoluble nature and inconsistencies between predicted and observed modes of RNA binding have restricted our understanding of their biological functions and their use as tools. We have used a consensus design strategy to create artificial PPR domains that are structurally robust and can be programmed for sequence-specific RNA binding. We solved the atomic structures of four of these artificial PPR domains, which enabled us to elucidate the structural basis for their stability and modelling of RNA-protein interactions provided mechanistic insights into the importance of RNA-binding residues and suggests modes of PPR-RNA association. The modular mode of RNA-binding by PPR proteins holds great promise for the engineering of new tools to target RNA and to understand the mechanisms of gene regulation by natural PPR proteins.