title: CPEB and miR-15/16 Co-Regulate Translation of Cyclin E1 mRNA during Xenopus Oocyte Maturation.
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.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ania
authors.initials: A
authors.lastname: Wilczynska
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Git
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Argasinska
authors.affiliation: Institute for Research in Biomedicine, Barcelona, Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Belloc
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nancy
authors.initials: N
authors.lastname: Standart
mesh_terms: D000818:Animals; D001483:Base Sequence; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008540:Meiosis; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism*; D009866:Oogenesis / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D039104:RNA 3' Polyadenylation Signals / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
chemical_list: C490388:Cpeb1 protein, Xenopus; D019927:Cyclin E; C000609088:MIRN15 microRNA, Xenopus; C000609089:MIRN16 microRNA, Xenopus; D035683:MicroRNAs; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex; D014157:Transcription Factors; D029867:Xenopus Proteins; C000609090:cyclin E1, Xenopus; D039221:mRNA Cleavage and Polyadenylation Factors
references.citation: Biol Cell. 2009 Sep;101(9):511-24
references.pmid: 19250063
references.citation: Cancer Res. 2009 Jul 1;69(13):5553-9
references.pmid: 19549910
references.citation: RNA. 2009 Aug;15(8):1433-42
references.pmid: 19535464
references.citation: Genes Dev. 2009 Aug 1;23(15):1743-8
references.pmid: 19574298
references.citation: Cell Death Differ. 2010 Feb;17(2):215-20
references.pmid: 19498445
references.citation: Nat Rev Mol Cell Biol. 2010 Feb;11(2):113-27
references.pmid: 20094052
references.citation: Curr Biol. 2010 Feb 9;20(3):271-7
references.pmid: 20116247
references.citation: Curr Biol. 2010 Feb 9;20(3):265-70
references.pmid: 20116252
references.citation: Development. 2010 Mar;137(6):859-70
references.pmid: 20179092
references.citation: Methods. 2010 May;51(1):165-9
references.pmid: 20188836
references.citation: EMBO J. 2010 Jul 7;29(13):2182-93
references.pmid: 20531391
references.citation: Genome Res. 2010 Aug;20(8):1010-9
references.pmid: 20508147
references.citation: J Mol Biol. 2010 Sep 24;402(3):491-509
references.pmid: 20678503
references.citation: Mol Cell Biol. 1998 Oct;18(10):6152-63
references.pmid: 9742132
references.citation: RNA. 1999 Jan;5(1):27-38
references.pmid: 9917064
references.citation: Methods. 1999 Jan;17(1):46-51
references.pmid: 10075882
references.citation: EMBO J. 1999 Apr 15;18(8):2294-303
references.pmid: 10205182
references.citation: Genes Dev. 2007 Mar 15;21(6):682-93
references.pmid: 17369401
references.citation: Nucleic Acids Res. 2007;35(7):2167-76
references.pmid: 17355986
references.citation: Trends Biochem Sci. 2007 Jun;32(6):279-85
references.pmid: 17481902
references.citation: J Biol Chem. 2007 Dec 28;282(52):37389-401
references.pmid: 17942399
references.citation: Cell. 2008 Feb 8;132(3):434-48
references.pmid: 18267074
references.citation: Nature. 2008 Apr 24;452(7190):1017-21
references.pmid: 18385675
references.citation: Mol Cell. 2014 Jun 5;54(5):751-65
references.pmid: 24768538
references.citation: Mol Cell. 2014 Jun 5;54(5):737-50
references.pmid: 24768540
references.citation: Biochem Soc Trans. 2014 Aug;42(4):1238-45
references.pmid: 25110031
references.citation: Breast Cancer Res. 2008;10(3):R54
references.pmid: 18588681
references.citation: Nucleic Acids Res. 2008 Sep;36(16):5391-404
references.pmid: 18701644
references.citation: Nat Med. 2008 Nov;14(11):1271-7
references.pmid: 18931683
references.citation: Genome Res. 2009 Oct;19(10):1766-75
references.pmid: 19628731
references.citation: EMBO J. 2009 Oct 7;28(19):2945-58
references.pmid: 19713941
references.citation: BMB Rep. 2009 Nov 30;42(11):725-30
references.pmid: 19944013
references.citation: Nat Cell Biol. 2010 Oct;12(10):1014-20
references.pmid: 20818387
references.citation: RNA. 2010 Nov;16(11):2094-107
references.pmid: 20826699
references.citation: Nat Rev Genet. 2011 Feb;12(2):99-110
references.pmid: 21245828
references.citation: Proc Natl Acad Sci U S A. 2011 May 17;108(20):8281-6
references.pmid: 21536868
references.citation: Genes Dev. 2011 Jun 1;25(11):1121-31
references.pmid: 21576259
references.citation: Curr Opin Genet Dev. 2011 Aug;21(4):452-7
references.pmid: 21536428
references.citation: Nat Rev Cancer. 2011 Sep;11(9):644-56
references.pmid: 21822212
references.citation: Mol Cell. 2011 Oct 7;44(1):120-33
references.pmid: 21981923
references.citation: Nat Struct Mol Biol. 2011 Nov;18(11):1218-26
references.pmid: 21984184
references.citation: Nat Struct Mol Biol. 2011 Nov;18(11):1211-7
references.pmid: 21984185
references.citation: Genes Dev. 2012 Feb 15;26(4):356-68
references.pmid: 22345517
references.citation: Science. 2012 Apr 13;336(6078):233-7
references.pmid: 22422859
references.citation: Science. 2012 Apr 13;336(6078):237-40
references.pmid: 22499947
references.citation: Biochim Biophys Acta. 2012 Jun;1819(6):593-603
references.pmid: 22266130
references.citation: Nat Struct Mol Biol. 2012 Jun;19(6):577-85
references.pmid: 22664985
references.citation: Nat Struct Mol Biol. 2012 Jun;19(6):586-93
references.pmid: 22664986
references.citation: Nat Struct Mol Biol. 2012 Jun;19(6):603-8
references.pmid: 22635249
references.citation: EMBO Rep. 2012 Aug;13(8):716-23
references.pmid: 22677978
references.citation: Ageing Res Rev. 2012 Sep;11(4):460-72
references.pmid: 22542725
references.citation: Science. 2013 Apr 5;340(6128):82-5
references.pmid: 23559250
references.citation: Dev Biol. 2000 Apr 1;220(1):97-109
references.pmid: 10720434
references.citation: Dev Biol. 2000 Nov 15;227(2):706-19
references.pmid: 11071785
references.citation: Curr Biol. 2002 Jun 25;12(12):1027-33
references.pmid: 12123578
references.citation: Nucleic Acids Res. 2004;32(4):1325-34
references.pmid: 14982957
references.citation: J Biol Chem. 2004 Apr 23;279(17):17650-9
references.pmid: 14752101
references.citation: RNA. 2004 Oct;10(10):1518-25
references.pmid: 15337849
references.citation: Genes Dev. 1992 Dec;6(12B):2580-91
references.pmid: 1285126
references.citation: J Biol Chem. 1995 Mar 24;270(12):6843-55
references.pmid: 7896832
references.citation: EMBO J. 1996 Feb 15;15(4):900-9
references.pmid: 8631310
references.citation: J Cell Sci. 1996 Jun;109 ( Pt 6):1173-84
references.pmid: 8799808
references.citation: J Cell Sci. 1996 Jun;109 ( Pt 6):1555-63
references.pmid: 8799842
references.citation: RNA. 2009 Dec;15(12):2351-63
references.pmid: 19854872
references.citation: Nucleic Acids Res. 2010 Jan;38(1):239-52
references.pmid: 19850724
references.citation: J Cell Sci. 2005 Mar 1;118(Pt 5):981-92
references.pmid: 15731006
references.citation: Cell. 2005 Mar 11;120(5):623-34
references.pmid: 15766526
references.citation: Science. 2006 Apr 7;312(5770):75-9
references.pmid: 16484454
references.citation: EMBO J. 2006 Jun 21;25(12):2792-801
references.pmid: 16763568
references.citation: Mol Cell Biol. 2007 Mar;27(6):2240-52
references.pmid: 17242205
references.citation: Genes Dev. 2007 Mar 15;21(6):644-8
references.pmid: 17369397
references.citation: RNA. 2014 Sep;20(9):1398-409
references.pmid: 25035296
references.citation: BMC Dev Biol. 2009;9:7
references.pmid: 19175933
references.citation: Clin Chem. 2009 Apr;55(4):611-22
references.pmid: 19246619
references.citation: Reproduction. 2009 Apr;137(4):595-617
references.pmid: 19225045
references.citation: RNA. 2009 May;15(5):781-93
references.pmid: 19304925
references.citation: Nat Cell Biol. 2009 May;11(5):652-8
references.pmid: 19377467