Deadenylation of alpha 1-acid glycoprotein mRNA in cultured hepatic cells during stimulation by dexamethasone.

During acute phase induction in rats, alpha 1-acid glycoprotein (AGP) mRNA is modified by a reduction in poly(A) tail size (Shiels, B.R., Northemann, W., Gehring, M.R., and Fey, G.H. (1987) J. Biol. Chem. 262, 12826-12831). In the studies presented here, we analyzed AGP mRNA induction and poly(A) tail modification in both primary rat hepatocytes and in the rat hepatoma cell line HTC. Poly(A) tail shortening occurred during stimulation by both glucocorticoids and hepatocyte stimulating factor. Induction of AGP by the glucocorticoid dexamethasone resulted in an approximately 50-fold increase in transcription by 4 h, which was followed by an equally rapid decrease. The large mRNA pool that resulted from this early burst of transcription was very stable, having a half-life of well over 24 h, and the individual molecules in this pool had an average poly(A) tail length of 200-250 bases. This stable pool of AGP mRNAs was then deadenylated to form a pool with an average tail length of 20-50 bases; the time course of this shortening followed that seen in the liver. Ongoing RNA synthesis, but not ongoing protein synthesis, was required for shortening of the tail. In contrast to the conclusion of Shiels et al. (1987), our data indicate that deadenylation occurs in the cytoplasm rather than the nucleus. Our data also suggest that shortening of AGP mRNA represents a specific example of the general deadenylation seen in earlier studies of total cellular RNA.