Novel mechanism for translational control in regulation of ferritin synthesis by iron

Abstract

Poly(A)-containing RNA was isolated from the polyribosomal and post-ribosomal fractions of the livers of normal and iron-treated rats. These RNA fractions were then translated in a wheat germ system to provide a measure of the amount of ferritin mRNA present in each fraction. Following iron administration, there was a 2-fold increase in the amount of ferritin mRNA in the polyribosomal fraction. This increase was not inhibited by prior treatment of the rats with actinomycin D or cordycepin, suggesting a cytoplasmic control mechanism. In normal rats, the post-ribosomal fraction contained an amount of ferritin mRNA equal to that in the polyribosomes. When iron was administered, this untranslated ferritin mRNA became reduced to negligible quantities, thus accounting for the doubling of the ferritin mRNA content of the polyribosomal fraction. A scheme is proposed in which translation of the ferritin mRNA in the post-ribosomal fraction is prevented by adhering ferritin subunits. Iron administration removes this inhibition of the translation of ferritin mRNA by promoting aggregation of these subunits into ferritin.