Facilitator oligonucleotides increase ribozyme RNA binding to full-length RNA substrates in vitro.
Primer extension arrest (PEA) studies have demonstrated that antisense oligonucleotides (beta 112C, beta 114C), which lie upstream of a ribozyme targeted to beta-amyloid peptide precursor (beta APP) mRNA, but not sense oligonucleotides (beta 112S, beta 116S) or a scrambled oligonucleotide, beta 116 M, affect ribozyme-mediated cleavage in vitro. Substrate dissociation experiments revealed that the ribozyme binding site in this mRNA was masked; PEA kinetics showed the association of the ribozyme and substrate was enhanced by antisense oligonucleotide binding. These studies suggest that masked ribozyme cleavage sites that may occur in disease-causing mRNAs can be targeted for degradation using "facilitator" oligonucleotides.
Denman
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Department of Molecular Biology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001483:Base Sequence; D007700:Kinetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016337:RNA, Catalytic / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D016564:Amyloid beta-Protein Precursor; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic; D012333:RNA, Messenger