Effect of lead on globin mRNA in vivo and in vitro

The total amount of mRNA recovered from Pb²⁺-treated rabbits was not significantly influenced by lead but dose-dependent loss of template activity of the poly A+ fraction was observed. These observations lead to the conclusion that the messenger RNA of rabbit reticulocytes exposed to Pb²⁺ in vivo was damaged and inactivated without extensive depolymerization of the mRNA. In vitro,/u> experiments on the effect of Pb²⁺ on purified rabbit globin mRNA were also performed. After incubation with Pb²⁺ at micromolar concentrations, the 7-methyl guanosine cap was removed from the mRNA, while damage to the remainder of the molecule seems to be slight. These data indicate that Pb²⁺ causes the loss of the template activity of reticulocyte mRNA in vivo by causing a nucleolytic cleavage of the mRNA at or near to the 5' cap.