AN ESTROGEN-INDUCIBLE PROTEIN BINDS SPECIFICALLY TO A SEQUENCE IN THE3' UNTRANSLATED REGION OF ESTROGEN-STABILIZED VITELLOGENIN MESSENGER-RNA

The 3' untranslated region (3'-UTR) has been implicated in the estroge n stabilization of hepatic Xenopus laevis vitellogenin mRNA. We used R NA gel mobility shift assays to demonstrate that Xenopus liver contain s a factor which binds with very high specificity to a segment of the 3'-UTR of vitellogenin B1 and B2 mRNAs. We detected a single high-affi nity binding site in the vitellogenin mRNA 3'-UTR and localized the bi nding site to a 27-nucleotide region. Since binding was abolished by p roteinase K digestion, at least a component of the factor is a protein . Following estrogen administration, binding was induced approximately four- to fivefold in extracts from liver polysomes. The hepatic vitel logenin mRNA-binding protein was found in both polysomes and cytosol. Since the protein was also estrogen inducible in cytosol, this represe nts a genuine induction, not simply recruitment of the cytosolic prote in into polysomes. UV cross-linking studies with the 27-nucleotide rec ognition sequence revealed bands corresponding to bound proteins with apparent molecular weights of 71,000 and 141,000. This appears to be t he first example of steroid hormone-inducible proteins binding to an m RNA 3'-UTR. Its induction by estrogen and its sequence-specific bindin g to a region of vitellogenin mRNA important in estrogen-mediated stab ilization suggest that the protein may play a role in the regulation o f mRNA stability.