Apical Loop−Internal Loop Interactions:  A New RNA−RNA Recognition Motif Identified through in Vitro Selection against RNA Hairpins of the Hepatitis C Virus mRNA

We performed in vitro selection of oligoribonucleotides in order to identify high-affinity motifs recognizing RNA hairpins located at the 3‘ end (SL1) and at the 5‘ end (domain IV of the internal ribosome entry site) of the hepatitis C virus mRNA. We selected aptamers constituted by an internal loop complementary to the SL1 apical loop, flanked by G-C-rich double-stranded regions, able to form complexes with a K d of 70 nM, at 37 °C under ionic conditions close to intracellular ones. The complex involves selective apical loop (SL1)−internal loop (aptamer) interactions. Similar structurally organized aptamers were independently identified against domain IV and were shown to also give rise to such complexes. Apical loop−internal loop interaction could constitute a new recognition motif allowing specific intra- or intermolecular RNA−RNA association.