Translational control by cytoplasmic polyadenylation of c-mos mRNA is necessary for oocyte maturation in the mouse.
The c-mos proto-oncogene product is a key element in the cascade of events leading to meiotic maturation of vertebrate oocytes. We have investigated the role of cytoplasmic polyadenylation in the translational control of mouse c-mos mRNA and its contribution to meiosis. Using an RNase protection assay we show that optimal cytoplasmic polyadenylation of c-mos mRNA requires three cis elements in the 3' UTR: the polyadenylation hexanucleotide AAUAAA and two U-rich cytoplasmic polyadenylation elements (CPEs) located 4 and 51 nucleotides upstream of the hexanucleotide. When fused to CAT coding sequences, the wild-type 3' UTR of c-mos mRNA, but not a 3' UTR containing mutations in both CPEs, confers translational recruitment during maturation. This recruitment coincides with maximum polyadenylation. To assess whether c-mos mRNA polyadenylation is necessary for maturation of mouse oocytes, we have ablated endogenous c-mos mRNA by injecting an antisense oligonucleotide, which results in a failure to progress to meiosis II after emission of the first polar body. Such antisense oligonucleotide-injected oocytes could be efficiently rescued by co-injection of a c-mos mRNA carrying a wild-type 3' UTR. However, co-injection of a c-mos mRNA lacking functional CPEs substantially lowered the rescue activity. These results demonstrate that translational control of c-mos mRNA by cytoplasmic polyadenylation is necessary for normal development.
Gebauer
F
F
Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545.
Xu
W
W
Cooper
G M
GM
Richter
J D
JD
D000249:Adenosine Monophosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003593:Cytoplasm / Q000378:metabolism; D007700:Kinetics; D008540:Meiosis; D051379:Mice; D008969:Molecular Sequence Data; D009866:Oogenesis / Q000502:physiology*; D014176:Protein Biosynthesis; D017231:Proto-Oncogene Proteins c-mos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*
D012333:RNA, Messenger; D000249:Adenosine Monophosphate; D017231:Proto-Oncogene Proteins c-mos