Modulation of Messenger RNA Metabolism in Experimental Methyl Mercury Neurotoxicity

Abstract

We have investigated the effects of methyl mercury on mRNA metabolism in mouse brain cells in vivo. It was demonstrated that methyl mercury substantially reduces the rate of synthesis of ATP and poly(A)-segments of mRNAs. The molecular sizes of poly(A)-segments isolated from hnRNA and polysomal mRNA of the experimental animal brain are smaller than the dimensions of the same segments from the cellular RNA of intact mice. A fall in the mRNA polyadenylation rate seen under methyl mercury directly correlates with reduced metabolic stability (t_1/2) of the respective poly(A)+mRNA. The mean time of nuclear-cytoplasmic transport of these mRNAs(t₀ is substantially increased under methyl mercury. At the same time, methyl mercury has no effect on the metabolism of brain polysomal poly(A)-mRNA. Direct addition of methyl mercury to an in vitro system containing excess ATP failed to affect the activity of poly(A) polymerase isolated from the brain of intact mice. The poison-induced alterations in the poly(A)+mRNA metabolism bring about a considerable reduction of the poly(A)+-fraction's share in the total polysomal mRNA and dramatic fall in the intracellular polysomes concentration. All the alterations in the examined metabolic parameters well correlate both with a reduced ATP content in the brain tissue and decreased rate of total protein synthesis in brain cells. Proceeding from these results as well as data from the literature, we developed a hypothetical model of a general molecular mechanism whereby methyl mercury inhibits protein synthesis in the brain.

Key Words:

• methyl mercury
• neurotoxicity
• brain mRNA
• ATP