Phosphorothioate oligonucleotides block reverse transcription by the Rnase H activity associated with the HIV-1 polymerase.
We demonstrate the degradation of RNA bound to an antisense oligonucleotide by a reverse transcriptase enzyme-associated RNase H activity. We found that phosphorothioate oligonucleotides inhibit the RNase H activity by binding to AMV RT, rather than to the template RNA, whereas the RNase H activity of HIV-1 RT is not affected by the antisense phosphorothioate oligonucleotide. Selective inhibition of HIV-1 gene expression involves the degradation of the template RNA bound to the antisense phosphorothioate oligonucleotide by the RNase H activity associated with the HIV-1 polymerase.
Hatta
T
T
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
Takai
K
K
Yokoyama
S
S
Nakashima
H
H
Yamamoto
N
N
Takaku
H
H
D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D001483:Base Sequence; D015497:HIV-1 / Q000201:enzymology*; D008969:Molecular Sequence Data; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D016914:Ribonuclease H / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D009692:Nucleic Acid Heteroduplexes; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D012313:RNA; D012194:RNA-Directed DNA Polymerase; D016914:Ribonuclease H