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Dissociation of mRNA cytoplasmic polyadenylation from translational activation by structural modification of the 5'-UTR.

During early metazoan development, certain maternal mRNAs are translationally activated by elongation of their poly(A) tails. Bicoid ( bcd ) mRNA is a Drosophila maternal mRNA that is translationally activated by cytoplasmic polyadenylation during the first hour after egg deposition. The sequences necessary and sufficient to promote its poly(A) elongation, and hence translation, are contained within its 3'-untranslated region (UTR). The mechanism by which poly(A) elongation at the 3'-end affects translational initiation at the 5'-end remains unknown. To investigate this question, we have analyzed a bicoid mRNA whose 5'-UTR contains a short antisense sequence directed against a portion of the coding region. This mutated RNA is efficiently translated in vitro. After injection into Drosophila embryos, this RNA is stable and polyadenylated, but inefficiently translated. These experiments show that structural modification of the 5'-end of an mRNA can perturb the translational activation normally conferred by polyadenylation in vivo.