alpha-Fetoprotein gene expression. Control of alpha-fetoprotein mRNA levels in cultured rat hepatoma cells.

The expression of alpha-fetoprotein (AFP) was infestigated in a cloned cell culture derived from Morris hepatoma 7777, which shows a density-dependent variation in the AFP synthesis rate. The rate of secretion of AFP was found to be governed by the level of cytoplasmic mRNAAFP. Saturation hybridization of pulse-labeled RNA to excess cloned cDNAAFP was used to illustrate quantitatively how mRNAAFP is regulated in these tumor cells. It was found that the mRNAAFP level is primarily determined by its rate of transcription and mRNAAFP declines to 40% of its maximum level, and it accumulates at 20% of its maximum rate. The half-life of mRNAAFP was found to be 40 h, 5 to 6 times that of poly(A)-containing RNA. This difference in stability, in cells doubling every 20 h, results in a 2 1/2-fold increase in the fraction of mRNAAFP above that expected from the relative transcription rate of mRNAAFP. During maximal synthesis of AFP, mRNAAFP accumulates in the cytoplasm at a rate 25 times greater than an average middle abundance mRNA and 1000 times greater than the average low abundance mRNA. These results and the relatively high translational efficiency of mRNAAFP explain how cells can optimize production of an abundant protein.