Modification of human DNA-dependent RNA polymerase activity by cyclic GMP

The effect of low concentrations of cyclic GMP (guanosine 3':5'-cyclic monophosphate) on the in vitro enzymatic activities of DNA-dependent RNA polymerases isolated from human peripheral blood lymphocytes has been investigated. In agreement with earlier studies which employed isolated nuclei as the enzyme source, an increase in the activity of partially purified RNA polymerase I is observed in the presence of cyclic GMP (10(-8) to 10(-10)M). RNA polymerase II activity is inhibited by the presence of cyclic GMP at concentrations between 10(-4) and 10(-10)M. RNA polymerase III activity is stimulated in a bimodal fashion by the presence of cyclic GMP with maximal activity noted at 10(-8) to 10(-10) M and 10(-5)M. In addition, [3H]cyclic GMP binds specifically to chromatographic fractions which are known to contain RNA polymerases I, II and III. This binding to RNA polymerases II and III is apprarently less tenacious as demonstrated by dissociation studies. The observations provide additional evidence for a role for cyclic GMP in the regulation of RNA synthesis.