Selective inhibition of initial polyadenylation in isolated nuclei by low levels of cordycepin 5"-triphosphate.
The effect of cordycepin 5'-triphosphate on poly(A) synthesis was investigated in isolated rat hepatic nuclei. Nuclei were incubated in the absence and presence of exogenous primer in order to distinguish the chromatin-associated poly(A) polymerase from the "free" enzyme (Jacob, S.T., Roe, F.J. and Rose, K.M. (1976) Biochem. J. 153, 733--735). The chromatin-bound enzyme, which adds adenylate residues onto the endogenous RNA, was selectively inhibited at low concentrations of cordycepin 5'-triphosphate, 50% inhibition being achieved at 2microng/ml. At least 80 times more inhibitor was required for 50% reduction in the "free" nuclear poly(A) polymerase activity. Inhibition of DNA-dependent RNA synthesis also required higher concentrations of the nucleotide analogue. These data not only offer a mechanism for the selective inhibition of initial polyadenylation of heterogeneous nuclear RNA in vivo by cordycepin, but also provide a satisfactory explanation for the indiscriminate effect of the inhibitor on partially purified or "free" poly(A) and RNA polymerases.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D003839:Deoxyadenosines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism*; D011062:Polynucleotide Adenylyltransferase / Q000037:antagonists & inhibitors; D012313:RNA / Q000096:biosynthesis; D051381:Rats
D000227:Adenine Nucleotides; D003839:Deoxyadenosines; D011061:Poly A; D012313:RNA; D011062:Polynucleotide Adenylyltransferase; D012321:DNA-Directed RNA Polymerases