Translational unmasking of Emi2 directs cytostatic factor arrest in meiosis II.
Cytostatic factor (CSF) arrests unfertilized vertebrate eggs in metaphase of meiosis II by inhibiting the anaphase-promoting complex/cyclosome (APC/C) from mediating cyclin destruction. The APC/C inhibitor Emi2/XErp1 satisfies a number of historical criteria for the molecular identification of CSF, but the mechanism by which CSF is activated selectively in meiosis II is the remaining unexplained criterion. Here we provide an explanation by showing that Emi2 is expressed specifically in meiosis II through translational de-repression or "unmasking" of its mRNA. We find that Emi2 protein is undetectable in immature, G2/prophase-arrested Xenopus oocytes and accumulates approximately 90 minutes after germinal vesicle breakdown. The 3' untranslated region of Emi2 mRNA contains cytoplasmic polyadenylation elements that directly bind the CPEB protein and confer temporal regulation of Emi2 polyadenylation and translation. Our results demonstrate that cytoplasmic polyadenylation and translational unmasking of Emi2 directs meiosis II-specific CSF arrest.
Tung
Jeffrey J
JJ
Genentech, Inc., South San Francisco, California, USA.
Padmanabhan
Kiran
K
Hansen
David V
DV
Richter
Joel D
JD
Jackson
Peter K
PK
D000818:Animals; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D005260:Female; D008540:Meiosis / Q000235:genetics*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D017231:Proto-Oncogene Proteins c-mos / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011817:Rabbits; D014981:Xenopus; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D044783:F-Box Proteins; C498166:FBXO43 protein, Xenopus; D029867:Xenopus Proteins; D017231:Proto-Oncogene Proteins c-mos