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

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Abstract
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.