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Molecular and Cellular Biology, April 1999, p. 2485-2494, Vol. 19, No. 4
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.
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
*
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.
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