AN RNA MOTIF THAT BINDS ATP

RNAs that contain specific high-affinity binding sites for small molec ule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecu les1,2. Here we describe a new in vitro selection procedure designed t o ensure the isolation of RNAs that bind the ligand of interest in sol ution as well as on a solid support. We have used this method to isola te a remarkably small RNA motif that binds ATP, a substrate in numerou s biological reactions and the universal biological high-energy interm ediate. The selected ATP-binding RNAs contain a consensus sequence, em bedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is chara cterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.