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Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein PCBP4 via mRNA stability

Ariane Scoumanne1, Seong Jun Cho, Jin Zhang

  • 1The Center for Comparative Oncology, University of California at Davis, Davis, CA 95616, USA.

Nucleic Acids Research
|September 7, 2010
PubMed

Insights

Poly(C)-binding protein 4 (PCBP4) regulates p21 expression by binding its mRNA. PCBP4 deficiency enhances p21 induction, impacting cell cycle and apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • RNA-binding proteins (RBPs) are crucial for post-transcriptional gene regulation.
  • PCBP4, a poly(C)-binding protein family member, is a p53 target involved in cell-cycle arrest and apoptosis.

Purpose of the Study:

  • To identify RNA targets of PCBP4 and elucidate its regulatory mechanisms.
  • To investigate PCBP4's role in p21 expression, independent of p53.

Main Methods:

  • Generation of cell lines with inducible PCBP4 overexpression and knockdown.
  • Creation of PCBP4-deficient mice and primary mouse embryo fibroblasts.
  • In vitro and in vivo binding assays to identify PCBP4-p21 transcript interactions.

Main Results:

  • PCBP4 expression suppresses p21 induction following DNA damage.
  • PCBP4 deficiency enhances p21 induction, even without p53.
  • PCBP4 directly binds the 3'-UTR of p21 mRNA, regulating its stability.

Conclusions:

  • PCBP4 acts as a negative regulator of both basal and stress-induced p21 expression.
  • Regulation occurs via direct binding to the p21 3'-UTR, modulating mRNA stability.
  • PCBP4's role in p21 regulation offers insights into cell cycle control and DNA damage response.

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