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AUF1 ligand circPCNX reduces cell proliferation by competing with p21 mRNA to increase p21 production

Dimitrios Tsitsipatis1, Ioannis Grammatikakis2, Riley K Driscoll1

  • 1Laboratory of Genetics and Genomics, National Institute on Aging (NIA) Intramural Research Program (IRP), National Institutes of Health (NIH), Baltimore, MD, USA.

Nucleic Acids Research
|January 14, 2021
PubMed

Insights

Circular RNAs (circRNAs) like circPCNX bind to the AUF1 protein, stabilizing p21 mRNA. This interaction inhibits cell proliferation by increasing p21 protein levels, a key cell cycle regulator.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Mammalian circular RNAs (circRNAs) regulate cellular functions through interactions with proteins and nucleic acids.
  • The cancer-related protein AUF1 is known to bind to various RNA molecules.
  • Understanding circRNA-protein interactions is crucial for deciphering gene regulation in cancer.

Purpose of the Study:

  • To systematically identify circRNAs interacting with the cancer-related protein AUF1.
  • To investigate the functional role of a specific AUF1-interacting circRNA, hsa_circ_0032434 (circPCNX), in regulating p21 mRNA stability and cell proliferation.

Main Methods:

  • Ribonucleoprotein immunoprecipitation (RIP) analysis to identify circRNA-protein interactions.
  • Overexpression and silencing of circPCNX in HeLa cells.
  • Assessment of AUF1 binding to p21 mRNA using molecular assays.
  • Measurement of p21 mRNA stability and protein production.
  • Analysis of cell proliferation rates.

Main Results:

  • circPCNX was identified as an abundant circRNA interacting with AUF1 in human cervical carcinoma cells.
  • Overexpression of circPCNX inhibited AUF1 binding to p21 mRNA, increasing p21 mRNA stability and protein levels, thereby suppressing cell proliferation.
  • Silencing circPCNX enhanced AUF1 binding to p21 mRNA, decreasing p21 production and promoting cell division.
  • Disruption of the AUF1-binding region on circPCNX abolished the effects on p21 levels and cell proliferation.

Conclusions:

  • circPCNX interacts with AUF1 to selectively prevent its binding to p21 mRNA.
  • This interaction enhances p21 mRNA stability and protein production, leading to the suppression of cell growth.
  • circPCNX acts as a regulator of cell proliferation by modulating the AUF1-p21 mRNA axis.

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