Enhancement by theophylline of the butyrate-mediated induction of choriogonadotropin alpha-subunit in HeLa cells. II. Effect of both agents on mRNA turnover.

In the accompanying paper it was demonstrated that among several methylxanthine phosphodiesterase inhibitors, only theophylline significantly increased production of the glycoprotein hormone alpha-subunit in HeLa cells, and that this action was synergistic with that of sodium butyrate. A correlation between alpha-subunit induction and cAMP concentrations was not evident. In this report we characterized the effect of these two drugs on the metabolism of alpha-subunit mRNA. Sodium butyrate decreased the apparent half-life of mRNAs encoding alpha-subunit, beta 2-microglobulin, and alpha-tubulin, as well as that of total poly(A)+ RNA and rRNA. Theophylline produced a two- to threefold increase in the apparent half-life of alpha-subunit mRNA but had no effect on the turnover of beta 2-microglobulin, alpha-tubulin, or total poly(A)+ mRNA. An inverse correlation was noted between the apparent half-life of the mRNA and the degree of destabilization elicited by butyrate. It is concluded that alpha-subunit induction by theophylline is in large part due to mRNA stabilization, and that the concerted effect of theophylline and butyrate results from inhibition by theophylline of the butyrate-mediated destabilization of alpha-subunit mRNA combined with the elevation in alpha-subunit gene transcription known to be produced by the fatty acid.