title: Gene suppression via U1 small nuclear RNA interference (U1i) machinery using oligonucleotides containing 2'-modified-4'-thionucleosides.
abstract: Gene suppression via U1 small nuclear RNA interference (U1i) is considered to be one of the most attractive approaches, and takes the place of general antisense, RNA interference (RNAi), and anti-micro RNA machineries. Since the U1i can be induced by short oligonucleotides (ONs), namely U1 adaptors consisting of a 'target domain' and a 'U1 domain', we prepared adaptor ONs using 2'-modified-4'-thionucleosides developed by our group, and evaluated their U1i activity. As a result, the desired gene suppression via U1i was observed in ONs prepared as a combination of 2'-fluoro-4'-thionucleoside and 2'-fluoronucleoside units as well as only 2'-fluoronucleoside units, while those prepared as combination of 2'-OMe nucleoside/2'-OMe-4'-thionucleoside and 2'-fluoronucleoside units did not show significant activity. Measurement of Tm values indicated that a higher hybridization ability of adaptor ONs with complementary RNA is one of the important factors to show potent U1i activity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokushima, Shomachi 1-78-1, Tokushima 770-8505, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Naoshi
authors.initials: N
authors.lastname: Yamazaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Tarashima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Furukawa
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Kohji
authors.initials: K
authors.lastname: Itoh
authors.forename: Noriaki
authors.initials: N
authors.lastname: Minakawa
mesh_terms: D001483:Base Sequence; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism*; D013872:Thionucleosides / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; D012342:RNA, Small Nuclear; D013872:Thionucleosides; C405483:U1 small nuclear RNA
keywords: 2′-Modified-4′-thioRNA; Gene suppression; Oligonucleotide; U1 snRNA interference