title: The WEE1 regulators CPEB1 and miR-15b switch from inhibitor to activators at G2/M.
abstract: MicroRNAs (miRNAs) in the AGO-containing RISC complex control messenger RNA (mRNA) translation by binding to mRNA 3' untranslated region (3'UTR). The relationship between miRNAs and other regulatory factors that also bind to mRNA 3'UTR, such as CPEB1 (cytoplasmic polyadenylation element-binding protein), remains elusive. We found that both CPEB1 and miR-15b control the expression of WEE1, a key mammalian cell cycle regulator. Together, they repress WEE1 protein expression during G1 and S-phase. Interestingly, the 2 factors lose their inhibitory activity at the G2/M transition, at the time of the cell cycle when WEE1 expression is maximal, and, moreover, rather activate WEE1 translation in a synergistic manner. Our data show that translational regulation by RISC and CPEB1 is essential in cell cycle control and, most importantly, is coordinated, and can be switched from inhibition to activation during the cell cycle.
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.
authors.forename: Gueorgui
authors.initials: G
authors.lastname: Kratassiouk
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Pritchard
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.|d Inserm U1016, Institut Cochin, Département Génétique et Développement , Paris , France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cuvellier
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.|e Department of Translation Mechanisms , Institute of Molecular Biology and Genetics, National Academy of Sciences , Kiev , Ukraine.
authors.forename: Andrii
authors.initials: A
authors.lastname: Vislovukh
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.|f The Breast Department of the Third Affiliated Hospital of Harbin Medical University , Harbin , China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Meng
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.
authors.forename: Regina
authors.initials: R
authors.lastname: Groisman
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Degerny
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Deforzh
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.
authors.forename: Annick
authors.initials: A
authors.lastname: Harel-Bellan
authors.affiliation: a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.|b Centre National de la Recherche Scientifique (CNRS) , Gif-Sur-Yvette , France.|c Commissariat à l'Energie Atomique (CEA) , Saclay, Gif-sur-Yvette , France.
authors.forename: Irina
authors.initials: I
authors.lastname: Groisman
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014157:Transcription Factors / Q000502:physiology*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000502:physiology*
chemical_list: C490386:CPEB1 protein, human; D018797:Cell Cycle Proteins; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human
keywords: CPEB1; WEE1; cell cycle; cytoplasmic polyadenylation; miR-15b; translational regulation