Nejvíce citovaný článek - PubMed ID 24983972
Aurora kinase A is not involved in CPEB1 phosphorylation and cyclin B1 mRNA polyadenylation during meiotic maturation of porcine oocytes
Mammalian oocyte development depends on the temporally controlled translation of maternal transcripts, particularly in the coordination of meiotic and early embryonic development when transcription has ceased. The translation of mRNA is regulated by various RNA-binding proteins. We show that the absence of cytoplasmic polyadenylation element-binding protein 3 (CPEB3) negatively affects female reproductive fitness. CPEB3-depleted oocytes undergo meiosis normally but experience early embryonic arrest due to a disrupted transcriptome, leading to aberrant protein expression and the subsequent failure of embryonic transcription initiation. We found that CPEB3 stabilizes a subset of mRNAs with a significantly longer 3'UTR that is enriched in its distal region with cytoplasmic polyadenylation elements. Overall, our results suggest that CPEB3 is an important maternal factor that regulates the stability and translation of a subclass of mRNAs that are essential for the initiation of embryonic transcription and thus for embryonic development.
- Klíčová slova
- embryo, mRNA, oocyte, translation,
- MeSH
- 3' nepřekládaná oblast genetika MeSH
- embryonální vývoj genetika MeSH
- meióza genetika MeSH
- messenger RNA genetika metabolismus MeSH
- myši MeSH
- oocyty * metabolismus MeSH
- polyadenylace MeSH
- proteiny vázající RNA * metabolismus genetika MeSH
- stabilita RNA genetika MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 3' nepřekládaná oblast MeSH
- Cpeb3 protein, mouse MeSH Prohlížeč
- messenger RNA MeSH
- proteiny vázající RNA * MeSH
Oocyte meiotic maturation and embryogenesis are some of the most important physiological processes that occur in organisms, playing crucial roles in the preservation of life in all species. The post-transcriptional regulation of maternal messenger ribonucleic acids (mRNAs) and the post-translational regulation of proteins are critical in the control of oocyte maturation and early embryogenesis. Translational control affects the basic mechanism of protein synthesis, thus, knowledge of the key components included in this machinery is required in order to understand its regulation. Cytoplasmic polyadenylation element binding proteins (CPEBs) bind to the 3'-end of mRNAs to regulate their localization and translation and are necessary for proper development. In this study we examined the expression pattern of cytoplasmic polyadenylation element binding protein 2 (CPEB2) both on the mRNA (by real-time quantitative reverse transcription polymerase chain reaction, qRT-PCR) and protein (by Western blotting, WB) level, as well as its localization during the meiotic maturation of porcine oocytes and early embryonic development by immunocytochemistry (ICC). For the elucidation of its functions, CPEB2 knockdown by double-strand RNA (dsRNA) was used. We discovered that CPEB2 is expressed during all stages of porcine meiotic maturation and embryonic development. Moreover, we found that it is necessary to enable a high percentage of oocytes to reach the metaphase II (MII) stage, as well as for the production of good-quality parthenogenetic blastocysts.
- Klíčová slova
- CPEB2, CPEBs, embryonic development, oocyte maturation, translational control,
- MeSH
- 3' nepřekládaná oblast MeSH
- embryonální vývoj MeSH
- genový knockdown MeSH
- meióza * MeSH
- messenger RNA metabolismus MeSH
- oocyty cytologie metabolismus MeSH
- partenogeneze MeSH
- prasata MeSH
- proteiny vázající RNA genetika metabolismus MeSH
- těhotenství MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 3' nepřekládaná oblast MeSH
- messenger RNA MeSH
- proteiny vázající RNA MeSH
The tight correlation between mRNA distribution and subsequent protein localization and function indicate a major role for mRNA localization within the cell. RNA localization, followed by local translation, presents a mechanism for spatial and temporal gene expression regulation utilized by various cell types. However, little is known about mRNA localization and translation in the mammalian oocyte and early embryo. Importantly, fully-grown oocyte becomes transcriptionally inactive and only utilizes transcripts previously synthesized and stored during earlier development. We discovered an abundant RNA population in the oocyte and early embryo nucleus together with RNA binding proteins. We also characterized specific ribosomal proteins, which contribute to translation in the oocyte and embryo. By applying selected markers to mouse and human oocytes, we found that there might be a similar mechanism of RNA metabolism in both species. In conclusion, we visualized the localization of RNAs and translation machinery in the oocyte, that could shed light on this terra incognita of these unique cell types in mouse and human.
- MeSH
- embryo savčí metabolismus ultrastruktura MeSH
- kultivované buňky MeSH
- lidé MeSH
- messenger RNA analýza genetika MeSH
- myši MeSH
- oocyty metabolismus ultrastruktura MeSH
- proteiny vázající RNA analýza genetika MeSH
- proteosyntéza * MeSH
- transkriptom MeSH
- vývojová regulace genové exprese * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- messenger RNA MeSH
- proteiny vázající RNA MeSH
Although the involvement of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in the regulation of cytostatic factor (CSF) activity; as well as in microtubules organization during meiotic maturation of oocytes; has already been described in detail; rather less attention has been paid to the role of ERK1/2 in the regulation of mRNA translation. However; important data on the role of ERK1/2 in translation during oocyte meiosis have been documented. This review focuses on recent findings regarding the regulation of translation and the role of ERK1/2 in this process in the meiotic cycle of mammalian oocytes. The specific role of ERK1/2 in the regulation of mammalian target of rapamycin (mTOR); eukaryotic translation initiation factor 4E (eIF4E) and cytoplasmic polyadenylation element binding protein 1 (CPEB1) activity is addressed along with additional focus on the other key players involved in protein translation.
- Klíčová slova
- CPEB1, ERK1/2, MAP kinase, eIF4E, mTOR, oocyte, translation,
- MeSH
- cytoplazma genetika metabolismus MeSH
- eukaryotický iniciační faktor 4E metabolismus MeSH
- faktory štěpení a polyadenylace mRNA metabolismus MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- lidé MeSH
- meióza * MeSH
- messenger RNA genetika metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 1 metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 3 metabolismus MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- oocyty metabolismus MeSH
- polyadenylace MeSH
- proteosyntéza * MeSH
- signální transdukce MeSH
- TOR serin-threoninkinasy metabolismus MeSH
- vazba proteinů MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- eukaryotický iniciační faktor 4E MeSH
- faktory štěpení a polyadenylace mRNA MeSH
- messenger RNA MeSH
- mitogenem aktivovaná proteinkinasa 1 MeSH
- mitogenem aktivovaná proteinkinasa 3 MeSH
- mitogenem aktivované proteinkinasy MeSH
- TOR serin-threoninkinasy MeSH