Regulating mRNA translation with a kiss.

Loop-loop interactions mediate the recognition between RNA hairpins leading to the formation of so-called kissing complexes. Both the size and the sequence of the loop are critical for ensuring stable interaction. Using in vitro selection we have characterized a few loop sequences that lead to the formation of highly stable kissing complexes. These sequences constitute targets of interest for the rational design of RNA stem loop ligands. Such an appropriate target sequence was identified in a sub-domain of the Internal Ribosomal Entry Site (IRES) of the Hepatitis C Virus (HCV) mRNA. We synthesized chemically-modified RNA hairpins and demonstrated that they specifically reduced the expression of a HCV IRES driven reporter gene in cultured cells.