Genome-wide analysis reveals a switch in the translational program upon oocyte meiotic resumption

Abstract

During oocyte maturation, changes in gene expression depend exclusively on translation and degradation of maternal mRNAs rather than transcription. Execution of this translation program is essential for assembling the molecular machinery required for meiotic progression, fertilization, and embryo development. With the present study, we used a RiboTag/RNA-Seq approach to explore the timing of maternal mRNA translation in quiescent oocytes as well as in oocytes progressing through the first meiotic division. This genome-wide analysis reveals a global switch in maternal mRNA translation coinciding with oocyte re-entry into the meiotic cell cycle. Messenger RNAs whose translation is highly active in quiescent oocytes invariably become repressed during meiotic re-entry, whereas transcripts repressed in quiescent oocytes become activated. Experimentally, we have defined the exact timing of the switch and the repressive function of CPE elements, and identified a novel role for CPEB1 in maintaining constitutive translation of a large group of maternal mRNAs during maturation.

Translational Control of Xenopus Oocyte Meiosis: Toward the Genomic Era

“…Indeed, DNA replication and transcription are not taking place during meiotic divisions but only after fertilization, in the embryo. This translational program is well-conserved in mouse prophase-arrested oocytes [76]. However, not all the genes regulating M-phase progression are translationally repressed.…”

“…Zar2 and CPEB1 act in a similar manner-their degradation is necessary to remove the repression of translation operating in prophase. Using an approach based on 3 -UTR reporters, it has been shown that the removal of the inhibitory complex (de-repression) increases the rate of translation in prophase I-arrested oocytes [76]. Importantly, the translation of these reporters further increases during meiosis resumption, suggesting that the activation of the translation does not simply rely on the de-repression of mRNAs but requires the recruitment of activating complexes [76].…”

“…Using an approach based on 3 -UTR reporters, it has been shown that the removal of the inhibitory complex (de-repression) increases the rate of translation in prophase I-arrested oocytes [76]. Importantly, the translation of these reporters further increases during meiosis resumption, suggesting that the activation of the translation does not simply rely on the de-repression of mRNAs but requires the recruitment of activating complexes [76]. Interestingly, CPEB4 is a Class II protein that has been proposed to be part of the activating complex required for the late polyadenylation [18].…”

“…Interestingly, Cdk1 not only promotes the translation of the components of the de-adenylation machinery, it further modulates the activity of these proteins by phosphorylation, thus enabling a precise coupling between mRNA de-adenylation/degradation and meiosis progression. The translation of Btg4, Cnot8, Cnot6L, DCP1A, and DCP2 is activated during meiosis, demonstrating that stockpiled mRNA degradation is encoded by the translation program of the oocyte [76,113,118]. Additionally, Cdk1 phosphorylates Y-box binding protein 2 (YBX2) [120,121], as well as DCP1A and DCP2 [119], which, respectively, results in mRNA deprotection and activates the de-capping activity of DCP1A and DCP2.…”

Diversity of RNA-Binding Proteins Modulating Post-Transcriptional Regulation of Protein Expression in the Maturing Mammalian Oocyte

“…Piqué et al [22] described a code based on the number and relative position of CPEs and PBEs that determined the timing of Cpeb1-mediated translation in frog oocytes. A more recent study defined such a code in mouse oocyte mRNAs whereby the efficiency of translational repression and activation depended on the numbers and positions of CPEs relative to PASs [85]. Differentially timed translation activation can also be mediated by the sequential activation of RBPs, such as has been proposed for DAZL which is thought to be translationally activated during oocyte maturation by CPEB1 [34].…”