Post-transcriptional regulation of gene expression is ubiquitous and fundamental for the control of cell growth, differentiation and the complex developmental programs of multicellular eukaryotes. Despite this realization, the current tools that are available to study RNAs are limited in many respects. Recently we expanded the RNA recognition code of Pumilio and FBF homology (PUF) proteins, enabling RNA-binding proteins with programmable specificities to be designed. The design of proteins that can bind any RNA sequence of interest and modulate its function will be important to elucidate the mechanisms by which gene expression is controlled at the level of RNA and may provide potential therapeutics in the future.