The architectural transcription factor TCF-1 interacts directly with beta-catenin and activates transcription of various target genes that are important for early development and carcinogenesis. We selected an RNA aptamer that specifically bound to the beta-catenin-interacting N-terminal motif of TCF-1. Structural analysis revealed that it formed a stem-loop structure that was responsible for binding TCF-1 and contained a pair of internal loops. The RNA aptamer interfered with the binding of TCF-1 to beta-catenin and also inhibited the formation of TCF-1/beta-catenin complexes. Disruption of TCF-1/beta-catenin complexes could alter the transcriptional activity of TCF-1. Taken together our observations show that a rationally designed RNA aptamer can disrupt protein-protein interactions required for the formation of an active transcription complex. (C) 2004 Published by Elsevier Inc.