Calcium regulates a great variety of intracellular processes [l-4]. In muscular contraction [5] or the activation of adenylate [6,7], calcium, acting as a coupling or second messenger 141, binds to specific proteins like troponin [5] or calmodulin 16-81 to exert its action. In RNA synthesis, activation by calcium is not well understood. Calcium stimulates RNA synthesis in slices of ventricular tissue [9], GH3 cells [lo] and cultures of chicken pectoralis muscle [ 111. But only indirect evidence is available about the molecular mechanism of such activation. Calciumdependent protein kinases in the nuclei of rat liver cells [ 121, the participation of calcium in the phosphorylation of non-histone proteins [ 13,141 and the presence of calmodulin in the nuclei of some cells [15], suggests that calcium could stimulate RNA synthesis through interaction of calcium with calmodulin, activation of calcium-dependent protein kinases by this calcium-calmodulin complex, phosphorylation of specific non-histone proteins and, finally, derepession of the genome. To test this hypothesis, we have investigated the effects of calcium, calmodulin and the calmodulin inhibitor, chlorpromazine, on RNA synthesis in isolated nuclei from rat liver cells. The results on the stimulation of RNA synthesis by calcium were not confirmed by our study, which has shown instead that calcium inhibits RNA synthesis and that this effect (again unlike the previous hypothesis) is not dependent on calmodulin. 2. MATERIALS AND METHODS