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Molecular and Cellular Biology, April 1999, p. 2485-2494, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

p70S6K Controls Selective mRNA Translation during Oocyte Maturation and Early Embryogenesis in Xenopus laevis

Markus S. Schwab,1 Sang H. Kim,1 Naohiro Terada,2 Catarina Edfjäll,3 Sara C. Kozma,3 George Thomas,3 and James L. Maller1,*

Howard Hughes Medical Institute and Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado 802621; Division of Basic Sciences, National Jewish Medical Research Center, Denver, Colorado 802062; and Friedrich Meischer Institute, Basel, Switzerland3

Received 4 September 1998/Returned for modification 22 October 1998/Accepted 28 December 1998

In mammalian cells, p70S6K plays a key role in translational control of cell proliferation in response to growth factors. Because of the reliance on translational control in early vertebrate development, we cloned a Xenopus homolog of p70S6K and investigated the activity profile of p70S6K during Xenopus oocyte maturation and early embryogenesis. p70S6K 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 inhibitor of p70S6K activation, caused oocytes to undergo germinal vesicle breakdown earlier than control oocytes, and sensitivity to progesterone was increased. Injection of a rapamycin-insensitive, constitutively active mutant of p70S6K reversed the effects of rapamycin. However, increases in S6 phosphorylation were not significantly affected by rapamycin during maturation. mos mRNA, which does not contain a 5'-terminal oligopyrimidine tract (5'-TOP), was translated earlier, and a larger amount of Mos protein was produced in rapamycin-treated oocytes. In fertilized eggs rapamycin treatment increased the translation of the Cdc25A phosphatase, which lacks a 5'-TOP. Translation assays in vivo using both DNA and RNA reporter constructs with the 5'-TOP from elongation factor 2 showed decreased translational activity with rapamycin, whereas constructs without a 5'-TOP or with an internal ribosome entry site were translated more efficiently upon rapamycin treatment. These results suggest that changes in p70S6K activity during oocyte maturation and early embryogenesis selectively alter the translational capacity available for mRNAs lacking a 5'-TOP region.


* Corresponding author. Mailing address: Howard Hughes Medical Institute and Department of Pharmacology, University of Colorado School of Medicine, Biomedical Research Building, Room 433, 4200 East Ninth Ave., Denver, CO 80262-0236. Phone: (303) 315-7075. Fax: (303) 315-7160. E-mail: mallerj{at}essex.uchsc.edu.


Molecular and Cellular Biology, April 1999, p. 2485-2494, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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