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

ABSTRACT 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.

Download full-text


Available from: Peter Kent Jackson, May 08, 2015
15 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Cold Spring Harbor perspectives in biology 06/2011; 3(9):a002758. DOI:10.1101/cshperspect.a002758 · 8.68 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Emi2 (also called Erp1) inhibits the anaphase-promoting complex/cyclosome (APC/C) and thereby causes metaphase II arrest in unfertilized vertebrate eggs. Both the D-box and the zinc-binding region (ZBR) of Emi2 have been implicated in APC/C inhibition. However, it is not well known how Emi2 interacts with and hence inhibits the APC/C. Here we show that Emi2 binds the APC/C via the C-terminal tail, termed here the RL tail. When expressed in Xenopus oocytes and egg extracts, Emi2 lacking the RL tail fails to interact with and inhibit the APC/C. The RL tail itself can directly bind to the APC/C, and, when added to egg extracts, either an excess of RL tail peptides or anti-RL tail peptide antibody can dissociate endogenous Emi2 from the APC/C, thus allowing APC/C activation. Furthermore, and importantly, the RL tail-mediated binding apparently promotes the inhibitory interactions of the D-box and the ZBR (of Emi2) with the APC/C. Finally, Emi1, a somatic paralog of Emi2, also has a functionally similar RL tail. We propose that the RL tail of Emi1/Emi2 serves as a docking site for the APC/C, thereby promoting the interaction and inhibition of the APC/C by the D-box and the ZBR.
    Molecular biology of the cell 03/2010; 21(6):905-13. DOI:10.1091/mbc.E09-11-0974 · 4.47 Impact Factor
  • Source
    • " 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 ) ."
    [Show abstract] [Hide abstract]
    ABSTRACT: A period of oocyte growth is followed by a process called oocyte maturation (the resumption of meiosis) which occurs prior to ovulation and is a prerequisite for successful fertilization. Our studies using fish models have revealed that oocyte maturation is a three-step induction process involving gonadotropin (LH), maturation-inducing hormone (MIH), and maturation-promoting factor (MPF). LH acts on the ovarian follicle layer to produce MIH (17alpha, 20beta-dihydroxy-4-pregnen-3-one, 17alpha, 20beta-DP, in most fishes). The interaction of ovarian thecal and granulosa cell layers (two-cell type model), is required for the synthesis of 17alpha,20beta-DP. The dramatic increase in the capacity of postvitellogenic follicles to produce 17alpha,20beta-DP in response to LH is correlated with decreases in P450c17 (P450c17-I) and P450 aromatase (oP450arom) mRNA and increases in the novel form of P450c17 (P450c17-II) and 20beta-hydroxysteroid dehydrogenase (20beta-HSD) mRNA. Transcription factors such as Ad4BP/SF-1, Foxl2, and CREB may be involved in the regulation of expression of these steroidogenic enzymes. A distinct family of G-protein-coupled membrane-bound MIH receptors has been shown to mediate non-genomic actions of 17alpha, 20beta-DP. The MIH signal induces the de novo synthesis of cyclin B from the stored mRNA, which activates a preexisting 35 kDa cdc2 kinase via phosphorylation of its threonine 161 by cyclin-dependent kinase activating kinase, thus producing the 34 kDa active cdc2 (active MPF). Upon egg activation, MPF is inactivated by degradation of cyclin B. This process is initiated by the 26S proteasome through the first cut in its NH(2) terminus at lysine 57.
    Development Growth and Regeneration 07/2008; 50 Suppl 1(Suppl 1):S195-219. DOI:10.1111/j.1440-169X.2008.01019.x · 2.42 Impact Factor
Show more