p70(S6K) controls selective mRNA translation during oocyte maturation and early embryogenesis in Xenopus laevis

In mammalian cells, p70(S6K) plays a key role in translational control of c ell proliferation in response to growth factors. Because of the reliance on translational control in early vertebrate development, we cloned a Xenopus homolog of p70(S6K) and investigated the activity profile of p70(S6K) duri ng Xenopus oocyte maturation and early embryogenesis. p70(S6K) activity is high in resting oocytes and decreases to background levels upon stimulation of maturation with progesterone. During embryonic development, three peaks of activity were observed: immediately after fertilization, shortly before the midblastula transition, and during gastrulation. Rapamycin, an inhibit or of p70(S6K) activation, caused oocytes to undergo germinal vesicle break down earlier than control oocytes, and sensitivity to progesterone was incr eased. Injection of a rapamycin-insensitive, constitutively active mutant o f p70(S6K) reversed the effects of rapamycin. However, increases in S6 phos phorylation were not significantly affected by rapamycin during maturation. mos mRNA, which does not contain a 5'-terminal oligopyrimidine tract (5'-T OP), was translated earlier, and a larger amount of Mos protein was produce d in rapamycin-treated oocytes, In fertilized eggs rapamycin treatment incr eased the translation of the Cdc25A phosphatase, which lacks a 5'-TOP. Tran slation assays in vivo using both DNA and RNA reporter constructs with the 5'-TOP from elongation factor 2 showed decreased translational activity wit h rapamycin, whereas constructs without a 5'-TOP or with an internal riboso me entry site were translated more efficiently upon rapamycin treatment. Th ese results suggest that changes in p70(S6K) activity during oocyte maturat ion and early embryogenesis selectively alter the translational capacity av ailable for mRNAs lacking a 5'-TOP region.