Synthesis and breakdown of pppA2'p5'A2'p5'A and transient inhibiton of protein synthesis in extracts from interferon-treated and control cells

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 inhibiton 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 interferon-treated and control cells.