Translational Unmasking of Emi2 Directs Cytostatic Factor Arrest in Meiosis II

University of Massachusetts Amherst, Amherst Center, Massachusetts, United States
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 04/2007; 6(6):725-31. DOI: 10.4161/cc.6.6.3936
Source: PubMed


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.

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Available from: Peter Kent Jackson, May 08, 2015
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    • "The oocyte's arrest at MII also requires changes in poly(A) tail length, particularly of the mRNA encoding Emi2, an inhibitor of the anaphase promoting complex/cyclosome (Tunquist and Maller 2003). Emi2 is required specifically at MII to arrest meiotic progression, and this is controlled by CPEB-mediated cytoplasmic polyadenylation of Emi2 mRNA (Tung et al. 2007). This process of meiotic arrest is more complex, for it involves negative feedback loops that mediate not only the expression of CPE-containing RNAs, but ARE (AU-rich element)-containing mRNAs as well (Belloc and Mendez 2008). "
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    ABSTRACT: Translational control of specific mRNAs is a widespread mechanism of gene regulation, and it is especially important in pattern formation in the oocytes of organisms in which the embryonic axes are established maternally. Drosophila and Xenopus have been especially valuable in elucidating the relevant molecular mechanisms. Here, we comprehensively review what is known about translational control in these two systems, focusing on examples that illustrate key concepts that have emerged. We focus on protein-mediated translational control, rather than regulation mediated by small RNAs, as the former appears to be predominant in controlling these developmental events. Mechanisms that modulate the ability of the specific mRNAs to be recruited to the ribosome, that regulate polyadenylation of specific mRNAs, or that control the association of particular mRNAs into translationally inert ribonucleoprotein complexes will all be discussed.
    Full-text · Article · Jun 2011 · Cold Spring Harbor perspectives in biology
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    • "Although the mechanisms of expression, degradation, and activation of Emi2 are well known, how Emi2 interacts with and inhibits the APC/C is not well understood (Tung et al., 2007; Wu and Kornbluth, 2008). On the basis of the results with Emi1 (Miller et al., 2006), however, Emi2 has been thought to interact with and inhibit the APC/C via the C-terminal region containing the D-box and the ZBR. "
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    Full-text · Article · Mar 2010 · Molecular biology of the cell
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    • " the molecular pathway that shoulders the CSF activity has been fully charac - terized in Xenopus . Mos stabilizes MPF by inhibiting the APC / C - mediated cyclin B degradation , through a pathway that consists of Mos , MEK , MAPK , p90 ribo - somal S6 kinase ( p90 rsk ) and Erp1 ( also called Emi2 ) ( Inoue et al . 2007 ; Nishiyama et al . 2007 ; Tung et al . 2007 ) ."
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