Effect of ethanol, phenol, formamide, dimethyl sulfoxide, paromomycin, and deuterium oxide on the fidelity of translation in a brain cell-free system

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Abstract
The effects of 6 different agents (ethanol, phenol, formamide, dimethyl sulfoxide [DMSO], heavy water and a misreading-inducing antibiotic, paromomycin) on the activity and the accuracy of poly(U) translation were compared under a range (2.5-12 mM) of Mg2+ concentrations in a rat brain cell-free system. The effect of most of these agents was remarkably sensitive to the Mg2+ concentration under which the assay was made. Ethanol decreased the fidelity of translation, and the efficiency of ethanol was increased 3- to 10-fold by higher Mg2+ concentrations. The effect of paromomycin was identical with that of ethanol, despite its very different structure. Formamide, a RNA denaturant, increased the accuracy of translation under all Mg2+ concentrations tested. DMSO, another type of RNA denaturant, decreased the accuracy of translation under all Mg2+ concentrations tested. Phenol increased the accuracy of translation at high Mg2+ concentrations but decreased it at low Mg2+ concentrations. D2O did not change to any appreciable extent the accuracy of translation, at all the Mg2+ concentrations used. There exists a cooperativity between the effects of Mg2+ and ethanol, Mg2+ and paromomycin, and M2+ and DMSO on the fidelity of translation; no such cooperativity was detected between Mg2+ and formamide and between Mg2+ and D2O. The differential effects of DMSO and formamide are interpreted in terms of their different dielectric constants. The dielectric constant of DMSO is higher than that of water, while that of formamide is lower.