Differential effects of cordycepin triphosphate and 9 beta-D-arabinofuranosyladenine triphosphate on tRNA and 5 S RNA synthesis in isolated nuclei.
Although cordycepin 5'-triphosphate (3'-dATP), at low concentrations, preferentially inhibits chromatin-associated poly(A) synthesis in isolated nuclei, higher levels of the inhibitor prevent both rRNA (RNA polymerase I activity) and hnRNA (RNA polymerase II activity) synthesis in vitro (Rose, K.M., Bell, L.E. and Jacob, S.T. (1977) Nature 267, 178-180). The present studies demonstrate that this nucleotide can also inhibit tRNA and 5 S RNA synthesis (RNA polymerase III activity). At 50-200 microgram/ml, 3'-dATP inhibits incorporation of [3H]UTP into tRNA and 5 S RNA by approximately 65%, whereas the syntheses of these RNAs were completely blocked when [3H]GTP was used as the substrate. These data suggest the formation of poly(U) in the tRNA and 5 S RNA regions, which is resistant to 3'-dATP. In contrast, another ATP analog, Ara-ATP, which selectively inhibits poly(A) synthesis, does not block tRNA and 5 S RNA synthesis in isolated nuclei. The production of these RNA species in isolated nuclei is also insensitive to Ara-CTP and 2'-dATP. These data suggest that 3'-dATP exerts general inhibitory effects on RNA synthesis and further substantiate the conclusion that Ara-ATP is a selective inhibitor of the polyadenylation reaction in vitro.
D000818:Animals; D001088:Arabinonucleotides / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis*; D012343:RNA, Transfer / Q000096:biosynthesis*; D051381:Rats; D014740:Vidarabine / Q000031:analogs & derivatives*; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives
D001088:Arabinonucleotides; D003838:Deoxyadenine Nucleotides; D001084:Vidarabine Phosphate; C000101:ara-ATP; D012313:RNA; D012343:RNA, Transfer; D014740:Vidarabine