Rapid changes in poly (A)(+) mRNA content in growth stimulated fibroblasts following perturbations in protein synthesis

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Abstract
We have previously shown that when resting 3T6 cells are serum stimulated in the presence of inhibitors of protein synthesis, poly(A)(+) mRNA content increases extremely rapidly relative to cells stimulated in the absence of drug. Poly(A)(+) mRNA content nearly doubles within two hours, but then remains constant for at least ten hours (Johnson and Meister, '77). In this report we show that continuous exposure to both serum and cycloheximide are required to maintain this elevated mRNA level. Removal of either leads to an equally rapid decrease in poly(A)(+) mRNA content. If cycloheximide is withdrawn at either two or ten hours following serum stimulation in the presence of the drug, allowing the rapid (< 30 minutes) restoration of the rate of protein synthesis, we observe that poly(A)(+) mRNA content decreases within two hours to a level nearly equal to that found in resting cells prior to stimulation. If the drug is withdrawn but the serum stimulus is not, the rapid decrease in poly(A)(+) mRNA content is followed by an increase which is parallel to that which occurs in cultures stimulated in the absence of drug, but displaced from the latter by an interval approximately equal to the length of exposure of the drug. These results show that the mammalian cell is able to decrease as well as increase its content of poly(A)(+) mRNA in response to drug induced perturbations in the rate of protein synthesis. The changes in poly(A)(+) mRNA content occur extremely rapidly and may represent an attempt by the cell to correct the perturbation.