title: Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain.
abstract: AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.
authors.affiliation: Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016; CREST, Japan Science and Technology Agency, Saitama 332-0012; Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601; Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama 362-0806; and Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nomura
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Fukunaga
authors.forename: Kazuya
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Manabu
authors.initials: M
authors.lastname: Chiba
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iibuchi
authors.forename: Taku
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Gota
authors.initials: G
authors.lastname: Kawai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kozu
authors.forename: Taiichi
authors.initials: T
authors.lastname: Sakamoto
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D050676:Core Binding Factor Alpha 2 Subunit / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D006801:Humans; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D059372:Nucleotide Motifs; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D052157:Aptamers, Nucleotide; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D012996:Solutions; D004247:DNA
keywords: AML1; NMR structure; RNA aptamer; RUNX1; SELEX