title: Synthesis of small interfering RNAs containing acetal-type nucleoside analogs at their 3'-ends and analysis of their silencing activity and their ability to bind to the Argonaute2 PAZ domain.
abstract: In this study, we aimed to create small interfering RNAs (siRNAs) with increased silencing activities and nuclease resistance properties. Therefore, we designed and synthesized five types of siRNA containing acetal-type nucleoside analogs at their 3'-dangling ends. We found that the siRNA containing 1-O-(2,2,2-trifluoroethyl)-β-D-ribofuranose at the 3'-dangling end was the most potent among the synthesized siRNAs and showed more resistance to nucleolytic degradation by a 3' exonuclease than a natural RNA did. Thus, modification of siRNAs by addition of 1-O-(2,2,2-trifluoroethyl)-β-D-ribofuranose may hold promise as a means of improving the silencing activity and nuclease resistance of siRNAs.
authors.affiliation: Course of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Inada
authors.affiliation: United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Nakamoto
authors.affiliation: Department of Bio-molecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokogawa
authors.affiliation: Course of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. Electronic address: uenoy@gifu-u.ac.jp.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ueno
mesh_terms: D000080:Acetals / Q000737:chemistry*; D060565:Argonaute Proteins / Q000737:chemistry*; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D020868:Gene Silencing; D006801:Humans; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: C466422:AGO2 protein, human; D000080:Acetals; D060565:Argonaute Proteins; D034741:RNA, Small Interfering
keywords: Acetal linkage; Nuclease-resistant; PAZ domain; RNAi; siRNA