Enhancement by theophylline of the butyrate-mediated induction of choriogonadotropin α-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 α-subunit in HeLa cells, and that this action was synergistic with that of sodium butyrate. A correlation between α-subunit induction and cAMP concentrations was not evident. In this report we characterized the effect of these two drugs on the metabolism of α-subunit mRNA. Sodium butyrate decreased the apparent half-life of mRNAs encoding α-subunit, β₂-microglobulin, and α-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 α-subunit mRNA but had no effect on the turnover of β₂-microglobulin, α-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 α-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 α-subunit mRNA combined with the elevation in α-subunit gene transcription known to be produced by the fatty acid.