Synthesis and Breakdown of pppA2′p5′A2′p5′A and Transient Inhibition of Protein Synthesis in Extracts from Interferon-Treated and Control Cells

Incubation of the mouse l-cell-free system with a concentration of pppA2′p5′A2′p5′A [(2′-5′)An] just sufficient to inhibit protein synthesis results in formation of a high-molecular-weight, heatlabile inhibitor and enhanced ribonuclease activity and in the rapid breakdown of (2′-5′)An to ATP. The (2′-5′)An-enhanced ribonuclease activity is also unstable and in the absence of a (2′-5′)An-regenerating system inhibition of protein synthesis is transient. Although interferon treatment enhances the synthesis of (2′-5′)An, the rates of degradation of (2′-5′)An and levels of activatible nuclease are similar in extracts prepared from control or interferon-treated cells. Interestingly, the sensitivity of different cell-free systems to (2′-5′)An varies with the source of the cell-free systems and with the methods used in their preparation. There is, however, no obvious correlation between the sensitivities of the system and the rate of breakdown of (2′-5′)An. The significance of these results is discussed in relation to a possible control function for the (2′-5′)An system in both interferontreated and control cells.