The ribosomal A-site as an inspiration for the design of RNA binders

The specific binding of aminoglycoside antibiotics to the bacterial ribosomal decoding site (A-site) has inspired the study of RNA-small molecules interactions and the search for novel RNA binders. Among the numerous RNA targets studied so far, the A-site holds a unique place. It is among the few truly validated RNA targets for which naturally occurring ligands have been discovered as “cognate” binders. In addition, due to its encapsulating architecture, the A-site is a more discriminating RNA target when compared to other RNA sequences. Previous observations and current challenges for the designers of potent and specific RNA binders are discussed.