One RNA aptamer sequence, two structures: a collaborating pair that inhibits AMPA receptors

RNA is ideally suited for in vitro evolution experiments, because a single RNA molecule possesses both genotypic (replicable sequence) and phenotypic (selectable shape) properties. Using systematic evolution of ligands by exponential enrichment (SELEX), we found a single 58-nt aptamer sequence that assumes two structures with different functions, both of which are required to inhibit the GluR2 AMPA receptor channel. Yet, the two structures, once formed during transcription, appear to be incapable of interconverting through unfolding and refolding, presumably due to their extraordinary structural stability. Thus, our results suggest more broadly that natural RNA molecules can evolve to acquire alternative structures and associated functions. Such divergence of RNA phenotype may precede gene duplication at the genome level.