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The WEE1 regulators CPEB1 and miR-15b switch from inhibitor to activators at G2/M

Gueorgui Kratassiouk1,2,3, Linda L Pritchard1,2,3, Sylvain Cuvellier1,2,3,4

  • 1a Université Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution 3377 , Gif-Sur-Yvette , France.

Cell Cycle (Georgetown, Tex.)
|March 31, 2016
PubMed

Insights

MicroRNAs (miRNAs) and CPEB1 regulate WEE1 protein expression, switching from repression to activation during the cell cycle. This coordinated control is crucial for cell cycle progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) within the RNA-induced silencing complex (RISC) regulate messenger RNA (mRNA) translation by targeting the 3' untranslated region (3'UTR).
  • The interplay between miRNAs and other 3'UTR-binding regulatory factors, like cytoplasmic polyadenylation element-binding protein 1 (CPEB1), is not fully understood.
  • WEE1 is a critical mammalian cell cycle regulator whose expression is tightly controlled.

Purpose of the Study:

  • To investigate the coordinated roles of CPEB1 and miR-15b in regulating WEE1 expression.
  • To elucidate how these regulatory factors modulate WEE1 translation throughout the cell cycle.

Main Methods:

  • Analysis of miRNA and CPEB1 interactions with WEE1 mRNA.
  • Assessment of WEE1 protein expression levels across different cell cycle phases.
  • Investigation of translational control mechanisms involving RISC and CPEB1.

Main Results:

  • Both CPEB1 and miR-15b repress WEE1 protein expression during the G1 and S phases of the cell cycle.
  • These regulatory factors lose their inhibitory function at the G2/M transition.
  • CPEB1 and miR-15b synergistically activate WEE1 translation during the G2/M phase when WEE1 expression is highest.

Conclusions:

  • Translational regulation by RISC and CPEB1 is essential for mammalian cell cycle control.
  • The regulatory activity of RISC and CPEB1 on WEE1 translation is coordinated and dynamically switches from repression to activation during the cell cycle.
  • This switch in translational control is critical for managing WEE1 levels at specific cell cycle stages.
Keywords:
CPEB1WEE1cell cyclecytoplasmic polyadenylationmiR-15btranslational regulation

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