title: Rational optimization of the DSL ligase ribozyme with GNRA/receptor interacting modules.
abstract: The DSL ribozyme is a class of artificial ligase ribozymes with a highly modular architecture, which catalyzes template-directed RNA ligation on a helical substrate module that can be either covalently connected (cis-DSL) or physically separated (trans-DSL) from the catalytic module. Substrate recognition by the catalytic module is promoted by one or two sets of GNRA/receptor interactions acting as clamps in the cis or trans configurations, respectively. In this study, we have rationally designed and analyzed the catalytic and self-assembly properties of several trans-DSL ribozymes with different sets of natural and artificial GNRA-receptor clamps. Two variants newly designed in this study showed significantly enhanced catalytic properties with respect of the original trans-DSL construct. While this work allows dissection of the turnover and catalytic properties of the trans-DSL ribozyme, it also emphasizes the remarkable modularity of RNA tertiary structure for nano-construction of complex functions.
authors.affiliation: Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, Fukuoka 819-0395, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ishikawa
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Matsumura
authors.forename: Luc
authors.initials: L
authors.lastname: Jaeger
authors.forename: Tan
authors.initials: T
authors.lastname: Inoue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furuta
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Ikawa
mesh_terms: D001483:Base Sequence; D001698:Biomedical Engineering; D020134:Catalytic Domain; D015195:Drug Design; D007700:Kinetics; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D016337:RNA, Catalytic; D012313:RNA