Metal ion-induced site-selective RNA hydrolysis by use of acridine-bearing oligonucleotide as cofactor.
New types of noncovalent ribozyme-mimics for site-selective RNA scission are prepared by combining metal ions with oligonucleotides bearing an acridine. Lanthanide(III) ions and various divalent metal ions (Zn(II), Mn(II), Cu(II), Ni(II), Co(II), Mg(II), and Ca(II)) are employed without being bound to any sequence-recognizing moiety. The modified oligonucleotide forms a heteroduplex with the substrate RNA, and selectively activates the phosphodiester linkages in front of the acridine. As a result, these linkages are preferentially hydrolyzed over the others, even though the metal ions are not fixed anywhere. The scission is efficient under physiological conditions, irrespective of the sequence at the target site. Site-selective RNA scission is also successful with the combination of an oligonucleotide bearing an acridine at its terminus, another unmodified oligonucleotide, and the metal ion. In a proposed mechanism, the acridine pushes the unpaired ribonucleotide out of the heteroduplex and changes the conformation of RNA at the target site for the sequence-selective activation.
Kuzuya
Akinori
A
Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
Mizoguchi
Ryo
R
Morisawa
Fumi
F
Machida
Kenzo
K
Komiyama
Makoto
M
D000166:Acridines / Q000737:chemistry*; D001483:Base Sequence; D001665:Binding Sites; D002413:Cations, Divalent / Q000737:chemistry; D006868:Hydrolysis; D007700:Kinetics; D028581:Lanthanoid Series Elements / Q000737:chemistry; D008345:Manganese / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D018716:Molecular Mimicry; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry
D000166:Acridines; D002413:Cations, Divalent; D028581:Lanthanoid Series Elements; D008670:Metals; D009841:Oligonucleotides; D016337:RNA, Catalytic; D008345:Manganese; D012313:RNA; D015032:Zinc