Telomerase as a potential molecular target to study G-quartet phosphorothioates.
Inhibition of gene expression by phosphorothioate oligomers is complex and involves specific and nonspecific mechanisms. Oligomers that contain a G-quartet elicit distinct effects in vitro and in vivo that are dependent on the context of the G-quartet's occurrence within a sequence. The enzyme telomerase, a ribonucleoprotein, has a stretch of C residues in the RNA template, which are used to add terminal dG-rich telomeric repeats to the ends of chromosomes. Some but not all phosphorothioates containing a G-quartet, depending on the context of occurrence, inhibited telomerase activity in vitro. Non-G-quartet phosphorothioates did not inhibit this activity. Activities of control enzymes, such as reverse transcriptase or taq polymerase, were not affected by the G-quartet oligomers. Neither phosphodiester nor chimeric oligomers of a G-quartet-containing oligomer were as potent inhibition of telomerase activity as phosphorothioate oligomers. These results may provide a molecular target to study the effects of G-quartet-containing oligomers.
Sharma
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Oncology Division, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110, USA.
Hsiao
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Narayanan
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D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005354:Fibrosarcoma; D006147:Guanine; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000378:metabolism*; D013873:Thionucleotides; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D051996:Transcription Factor RelA; D006147:Guanine; D019098:Telomerase