%0 Journal Article
%T Photoswitching of Site-Selective RNA Scission by Sequential Incorporation of Azobenzene and Acridine Residues in a DNA Oligomer
%A Akinori Kuzuya
%A Keita Tanaka
%A Makoto Komiyama
%J Journal of Nucleic Acids
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/162452
%X Photoresponsive systems for site-selective RNA scission have been prepared by combining Lu(III) ions with acridine/azobenzene dual-modified DNA. The modified DNA forms a heteroduplex with substrate RNA, and the target phosphodiester linkages in front of the acridine residue is selectively activated so that Lu(III) ion rapidly cleaves the linkage. Azobenzene residue introduced adjacent to the acridine residue acts as a photoresponsive switch, which triggers the site-selective scission upon UV irradiation. A trans isomer of azobenzene efficiently suppresses the scission, whereas the cis isomer formed by UV irradiation hardly affects the scission. As a result, 1.7¨C2.4-fold acceleration of the cleavage was achieved simply by irradiating UV for 3£¿min to the mixture prior to the reaction. Considering the yield of photoisomerization, the intrinsic activity of a cis isomer is up to 14.5-fold higher than that of the trans isomer. 1. Introduction In this couple of decades, significant attention has been focused on site-selective RNA scission, since it is indispensable for future molecular biology and therapy [1¨C3]. Discovery of important roles of short RNA in living cells further promoted this [4]. We have recently developed efficient artificial systems for site-selective RNA scission by combining a metal ion (lanthanide ions or some transition metal ions) as molecular scissor and an acridine-modified DNA as a sequence selective RNA activator [5]. Either of the 5¡ä- or 3¡ä-phosphodiester linkage of the target nucleotide in front of the acridine moiety, which is in protonated form under neutral condition, is site-selectively activated through general acid catalysis [6]. When Lu(III) ion is used as the catalyst, the general acid catalysis preferentially promotes the cleavage at the 3¡ä-side linkage. In addition, conformational change of RNA backbone caused by acridine intercalation is thought to be another important factor in the activation. The other portions of RNA are protected from metal ion-induced hydrolysis by duplex formation with DNA additives. Sequence of the target site can be freely chosen, and the reaction is selective and efficient enough to achieve simultaneous tandem scission in close proximity as small as 10 nucleotides [7]. This technique has been applied to new genotyping methods for single-nucleotide (SNP) or insertion-deletion (indel) polymorphisms [8]. One significant advantage of this system is that any desired function can be added to it by additional modification to the acridine-modified DNA. One such example is the addition of a ligand to DNA
%U http://www.hindawi.com/journals/jna/2011/162452/