Natural antisense RNA/target RNA interactions: possible models for antisense oligonucleotide drug design.
Current antisense oligonucleotides designed for drug therapy rely on Watson-Crick base pairing for the specificity of interactions between antisense and target molecules. However, thermodynamically stable duplexes containing non-Watson-Crick pairs have been formed with synthetic oligonucleotides. There are also numerous examples of non-canonical base pairs that participate in stable intra- and inter-molecular RNA/RNA pairing in prokaryotic and eukaryotic cells. Several natural antisense RNA/target RNA duplexes contain looped-out and bulged positions as well as non-canonical pairs as exemplified by formation of the Escherichia coli antisense micF RNA/ompF mRNA duplex. Secondary structures and the phylogenetic conservation of nucleotide sequences are well characterized in this system. Natural antisense/ target interactions may serve as models for determining possible and optimal antisense/target interactions in oligonucleotide drug design.
Delihas
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Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook 11794-5222, USA.
Rokita
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SE
Zheng
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P
D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015195:Drug Design; D004926:Escherichia coli / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis*; D016372:RNA, Antisense / Q000737:chemistry*; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D016376:Oligonucleotides, Antisense; D016372:RNA, Antisense; D012329:RNA, Bacterial; D012333:RNA, Messenger