title: Cleavage of human MDR1 mRNA by a hammerhead ribozyme.
abstract: We designed a hammerhead ribozyme which site-specifically cleaved the GUC sequence in codon 179 of MDR1 mRNA. The cleavage site was 6 amino acids upstream from the drug binding site and was considered sufficiently close to the essential locus for P-glycoprotein function. The ribozyme cleaved the MDR1 mRNA under physiological conditions in vitro. The cleavage was dependent on ribozyme concentration and on incubation time. Mg2+ ion was essential for the cleavage. These results show that a potentially useful tool is at hand which may inactivate MDR1 mRNA and revert the multidrug resistance phenotype.
authors.affiliation: Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, NY 10029.
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Dorai
authors.forename: J F
authors.initials: JF
authors.lastname: Holland
authors.forename: T
authors.initials: T
authors.lastname: Ohnuma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001483:Base Sequence; D001665:Binding Sites; D003062:Codon; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D016337:RNA, Catalytic / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016597:Trimetrexate; D014407:Tumor Cells, Cultured; D014750:Vincristine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003062:Codon; D008562:Membrane Glycoproteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D014750:Vincristine; D016597:Trimetrexate