Anti-idiotype RNAs that mimic the leucine-rich nuclear export signal and specifically bind to CRM1/exportin 1

Background: Anti-idiotype approaches are based on the assumption that an an tibody recognising a ligand can be structurally related to the receptor. Re cently we have generated anti-idiotype RNA aptamers designed to mimic the h uman immunodeficiency virus-1 (HIV-1) Rev nuclear export signal (NES). Nucl ear injection of either NES-peptide conjugates or aptamer causes the inhibi tion of Rev-mediated export. This implied that NES mimics and export substr ate might compete for binding to the NES receptor. The mechanism of inhibit ion, however, is unknown, Results: The interaction between the export aptamer and CRM1 was characteri sed in vitro. The aptamer binds specifically to CRM1 and this interaction i s sensitive to competition by Rev NES-peptide conjugates. The recognition d omain of CRM1 has been mapped and includes residues found previously to aff ect binding of leptomycin B, a fungicide interfering with nuclear export. Conclusions: Inhibition of Rev-mediated export in vivo by export aptamers a ppears to result from the binding of the aptamers to the NES-recognition do main of CRM1. This observation demonstrates that anti-idiotype RNA can mimi c faithfully structural and functional properties of a protein and can be u sed to map ligand-binding domains of receptors.