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CPEB and miR-15/16 Co-Regulate Translation of Cyclin E1 mRNA during Xenopus Oocyte Maturation.


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Authors

Wilczynska, Ania 
Argasinska, Joanna 
Belloc, Eulàlia 

Abstract

Cell cycle transitions spanning meiotic maturation of the Xenopus oocyte and early embryogenesis are tightly regulated at the level of stored inactive maternal mRNA. We investigated here the translational control of cyclin E1, required for metaphase II arrest of the unfertilised egg and the initiation of S phase in the early embryo. We show that the cyclin E1 mRNA is regulated by both cytoplasmic polyadenylation elements (CPEs) and two miR-15/16 target sites within its 3'UTR. Moreover, we provide evidence that maternal miR-15/16 microRNAs co-immunoprecipitate with CPE-binding protein (CPEB), and that CPEB interacts with the RISC component Ago2. Experiments using competitor RNA and mutated cyclin E1 3'UTRs suggest cooperation of the regulatory elements to sustain repression of the cyclin E1 mRNA during early stages of maturation when CPEB becomes limiting and cytoplasmic polyadenylation of repressed mRNAs begins. Importantly, injection of anti-miR-15/16 LNA results in the early polyadenylation of endogenous cyclin E1 mRNA during meiotic maturation, and an acceleration of GVBD, altogether strongly suggesting that the proximal CPEB and miRNP complexes act to mutually stabilise each other. We conclude that miR-15/16 and CPEB co-regulate cyclin E1 mRNA. This is the first demonstration of the co-operation of these two pathways.

Description

Keywords

Animals, Base Sequence, Cyclin E, Female, Meiosis, MicroRNAs, Models, Biological, Molecular Sequence Data, Oocytes, Oogenesis, Protein Biosynthesis, RNA 3' Polyadenylation Signals, RNA, Messenger, RNA-Induced Silencing Complex, Transcription Factors, Xenopus Proteins, Xenopus laevis, mRNA Cleavage and Polyadenylation Factors

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

11

Publisher

Public Library of Science (PLoS)
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/E016316/1)
This study was supported by the Biotechnology and Biological Sciences Research Council (BB/E016316/1). AG was funded by Cancer Research UK and the RATHER consortium, and JA was funded by the Cambridge Overseas Trust and the Parke Davis Bursary (Downing College).