Lee Su Kyung, Park Min Woo, Yang Eun Gyeong, Yu Jaehoon, Jeong Sunjoo
Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Republic of Korea.
Biochem Biophys Res Commun. 2005 Feb 4;327(1):294-9. doi: 10.1016/j.bbrc.2004.12.011.
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.
结构转录因子TCF-1直接与β-连环蛋白相互作用,并激活对早期发育和致癌作用至关重要的各种靶基因的转录。我们筛选出一种RNA适体,它能特异性结合TCF-1与β-连环蛋白相互作用的N端基序。结构分析表明,它形成了一个茎环结构,该结构负责结合TCF-1并包含一对内环。该RNA适体干扰了TCF-1与β-连环蛋白的结合,也抑制了TCF-1/β-连环蛋白复合物的形成。TCF-1/β-连环蛋白复合物的破坏可能会改变TCF-1的转录活性。综合我们的观察结果表明,合理设计的RNA适体可以破坏活性转录复合物形成所需的蛋白质-蛋白质相互作用。