The WEE1 regulators CPEB1 and miR-15b switch from inhibitor to activators at G2/M |
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| Authors: | Gueorgui Kratassiouk Linda L Pritchard Sylvain Cuvellier Andrii Vislovukh Qingwei Meng Regina Groisman |
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| Institution: | 1. Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377, Gif-Sur-Yvette, France;2. Centre National de la Recherche Scientifique (CNRS), Gif-Sur-Yvette, France;3. Commissariat à l′Energie Atomique (CEA), Saclay, Gif-sur-Yvette, France;4. Inserm U1016, Institut Cochin, Département Génétique et Développement, Paris, France;5. Department of Translation Mechanisms, Institute of Molecular Biology and Genetics, National Academy of Sciences, Kiev, Ukraine;6. The Breast Department of the Third Affiliated Hospital of Harbin Medical University, Harbin, China |
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| 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. |
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| Keywords: | cell cycle CPEB1 cytoplasmic polyadenylation miR-15b translational regulation WEE1 |
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