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 fag polymerase, were not affected by the G-quartet oligomers. Neither phosphodiester nor chimeric oligomers of a G-quartet-containing oligomer were as potent in inhibition of telomerase activity as phosphorothioate oligomers, These results may provide a molecular target to study the effects of G-quartet-containing oligomers.