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Spindle-localized CPE-mediated translation controls meiotic chromosome segregation

Nature Cell Biology volume 10, pages 858–865 (2008)Cite this article

Abstract

Meiotic progression requires the translational activation of stored maternal mRNAs, such as those encoding cyclin B1 or mos. The translation of these mRNAs is regulated by the cytoplasmic polyadenylation element (CPE) present in their 3′UTRs, which recruits the CPE-binding protein CPEB1. This RNA-binding protein not only dictates the timing and extent of translational activation by cytoplasmic polyadenylation2,3 but also participates, together with the translational repressor Maskin, in the transport and localization, in a quiescent state, of its targets to subcellular locations where their translation will take place4. During the early development of Xenopus laevis, CPEB localizes at the animal pole of oocytes and later on at embryonic spindles and centrosomes5. Disruption of embryonic CPEB-mediated translational regulation results in abnormalities in the mitotic apparatus and inhibits embryonic mitosis5. Here we show that spindle-localized translational activation of CPE-regulated mRNAs, encoding for proteins with a known function in spindle assembly and chromosome segregation, is essential for completion of the first meiotic division and for chromosome segregation in Xenopus oocytes.

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Figure 1: Xkid and TPX2 mRNAs are cytoplasmically polyadenylated and translationally activated during meiotic maturation.
Figure 2: The 3′UTRs of Xkid and TPX2 mRNAs direct their localization to the spindles.
Figure 3: Localized translational activation of Xkid mRNA is required for the accumulation of Xkid protein.
Figure 4: Localized Xkid mRNA translation is required for MI–MII transition.
Figure 5: Localized translational activation of CPE-containing mRNAs is required for MI–MII transition.

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Acknowledgements

We thank Joel D. Richter for the anti-CPEB antibody, Angel Nebreda for Xkid cDNA and antibody, Edouard Bertrand and Robert H. Singer for MS2-binding sites and MS2–GFP cDNAs, Fátima Gebauer for the reporter plasmids pLuccassette and pRenilla and her helpful discussions, CRG-Microscopy Facility for technical advice and Mercedes Fernández, members of the Méndez laboratory, Juan Valcarcel and other colleagues from the Program of Gene Expression for helpful advice and critically reading the manuscript. This work was supported by grants from the MEC, Fundación 'La Caixa' and Fundació 'Marató de TV3'. R.M. is a recipient of a contract from the 'Programa Ramon y Cajal' (MEC). CE is recipient of a fellowship from the DURSI (Generalitat de Catalunya) i dels Fons Social Europeu.

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Authors and Affiliations

  1. Centre for Genomic Regulation (CRG), C/ Dr. Aiguader, 88, Barcelona, 08003, Spain

    Carolina Eliscovich, Isabel Peset, Isabelle Vernos & Raúl Méndez

  2. Institució Catalena de Reserca i Estudis Avançats (ICREA), Passeig Lluis Companys 23, Barcelona, 08010, Spain

    Isabelle Vernos

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  1. Carolina Eliscovich
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  2. Isabel Peset
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  4. Raúl Méndez
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Contributions

I.P. performed the experiments shown in Fig. 2c, d and f; C.E. performed the rest of the experiments; I.V. and R.M. contributed to the experimental design and prepared the manuscript.

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Correspondence to Raúl Méndez.

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Supplementary Figures S1, S2, S3, S4, S5, S6 (PDF 1376 kb)

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Eliscovich, C., Peset, I., Vernos, I. et al. Spindle-localized CPE-mediated translation controls meiotic chromosome segregation. Nat Cell Biol 10, 858–865 (2008). https://doi.org/10.1038/ncb1746

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