Loop Loop Interactions

Intramolecular RNA folding generates stem-loop structures that frequently constitute scaffolds for triggering a biological process or that are binding sites of proteins (Hentze and Kuhn, 1996; Altuvia and Wagner, 2000). These structures might therefore be targets of interest for the design of ligands that will interfere with these processes or compete with RNA-binding proteins. The different strategies developed over the last 15 years for targeting RNA sequences with nucleic acids are poorly adapted to the recognition of RNA structures (Toulmé et al., 2001). Indeed antisense oligonucleotides, ribozymes, or small interfering RNAs (siRNAs) require a single-stranded complementary sequence for binding. Intramolecular interactions involved in RNA structures weaken the association between the regulatory species (antisense, ribozyme, siRNA) and the target, and consequently the effect induced by these oligomers (Mir and Southern, 1999).

Different possibilities have been considered, including the design of high-affinity chemically modified oligonucleotides, which invade the structure and shift the equilibrium toward the unfolded form (Compagno et al., 1999). Oligonucleotides have also been designed that bind to the double-stranded stem of RNA hairpins (Brossalina and Toulmé, 1993; François et al., 1994; Le Tinévez et al., 1998). In vitro selection offers the unique opportunity to identify oligonucleotides that take advantage of structural peculiarities (loops, bulges, etc.) to establish both canonical (Watson-Crick base pairing) and non-canonical interactions.

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