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The impact of post-transcriptional regulation in the p53 network

Justin A Freeman1, Joaquin M Espinosa

  • 1HHMI - University of Colorado at Boulder, 347 UCB, Boulder, CO 80309, USA.

Briefings in Functional Genomics
|December 18, 2012
PubMed

Insights

The p53 transcription factor controls cellular stress responses. This review details how microRNAs (miRNAs) and RNA-binding proteins (RBPs) post-transcriptionally regulate p53 target mRNAs, influencing cell fate.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The p53 transcription factor is a critical regulator of cellular responses to stress.
  • p53 controls the expression of numerous genes involved in cell-cycle arrest, apoptosis, autophagy, and senescence.
  • Understanding the regulation of p53 target genes is crucial for comprehending cellular stress pathways.

Purpose of the Study:

  • To review the post-transcriptional regulation of p53 target mRNAs by microRNAs (miRNAs) and RNA-binding proteins (RBPs).
  • To elucidate how miRNAs and RBPs modulate the p53 transcriptional program in a context-dependent manner.
  • To discuss the interplay between p53, its direct miRNA/RBP targets, and protein-coding genes in orchestrating cellular responses.

Main Methods:

  • Literature review and synthesis of existing research on p53, miRNAs, and RBPs.
  • Analysis of post-transcriptional regulatory mechanisms affecting p53 target mRNAs.
  • Examination of the coordinated action of p53, miRNAs, RBPs, and protein-coding genes.

Main Results:

  • p53 target mRNAs are subject to concurrent post-transcriptional regulation by miRNAs and RBPs.
  • This regulation fine-tunes the p53 transcriptional output in a cell type- and stimulus-specific manner.
  • Specific miRNAs and RBPs, themselves transcriptional targets of p53, play a key role in this regulatory network.

Conclusions:

  • Post-transcriptional regulation by miRNAs and RBPs is integral to the p53 pathway.
  • The coordinated action of p53, its target miRNAs/RBPs, and protein-coding genes ensures precise cellular stress responses.
  • This regulatory network provides a deeper understanding of p53-mediated cellular fate decisions.

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