CPEB CONTROLS THE CYTOPLASMIC POLYADENYLATION OF CYCLIN, CDK2 AND C-MOS MESSENGER-RNAS AND IS NECESSARY FOR OOCYTE MATURATION IN XENOPUS

Cytoplasmic polyadenylation is a key mechanism controlling maternal mR NA translation in early development, In most cases, mRNAs that undergo poly(A) elongation are translationally activated; those that undergo poly(A) shortening are deactivated, Poly(A) elongation is regulated by two cis-acting sequences in the 3'-untranslated region (UTR) of respo nding mRNAs, the polyadenylation hexanucleotide AAUAAA and the U-rich cytoplasmic polyadenylation element (CPE), Previously, we cloned and c haracterized the Xenopus oocyte CPE binding protein (CPEB), showing th at it was essential for the cytoplasmic polyadenylation of B4 RNA, Her e, we show that CPEB also binds the CPEs of G10, c-mos, cdk2, cyclins A1, B1 and B2 mRNAs, We find that CPEB is necessary for polyadenylatio n of these RNAs in egg extracts, suggesting that this protein is requi red for polyadenylation of most RNAs during oocyte maturation, Our dat a demonstrate that the complex timing and extent of polyadenylation ar e partially controlled by CPEB binding to multiple target sites in the 3' UTRs of responsive mRNAs. Finally, injection of CPEB antibody into oocytes not only inhibits polyadenylation in vivo, but also blocks pr ogesterone-induced maturation. This is due to inhibition of polyadenyl ation and translation of c-mos mRNA, suggesting that CPEB is critical for early development.