Endogenous p53 expression in human and mouse is not regulated by its 3'UTR

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Updated: Nov 6, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Sibylle Mitschka1, Christine Mayr1

  • 1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, United States.

Elife
|May 6, 2021
PubMed

Insights

The tumor suppressor TP53

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The TP53 gene encodes the p53 tumor suppressor, crucial for preventing cancer.
  • Dysfunctional p53 is common in human cancers.
  • Post-transcriptional regulation of TP53, particularly via its 3'UTR, is implicated in tumorigenesis.

Purpose of the Study:

  • To investigate the role of the endogenous TP53 3'UTR in regulating p53 expression.
  • To validate previously observed regulatory effects of the isolated TP53 3'UTR in a native context.

Main Methods:

  • Utilized CRISPR/Cas9 gene editing to delete the 3'UTRs of human TP53 and mouse Trp53.
  • Maintained endogenous mRNA processing in the genetic models.
  • Employed reporter assays to assess gene expression regulation.

Main Results:

  • The endogenous TP53 3'UTR does not regulate p53 mRNA or protein levels.
  • Neither basal expression nor response to genotoxic stress is affected by the endogenous 3'UTR.
  • While isolated 3'UTRs showed repression in reporter assays, the TP53 coding region exerted a stronger dominant-negative effect, masking 3'UTR contributions.

Conclusions:

  • The endogenous TP53 3'UTR is not a significant regulator of p53 expression.
  • Genetic models are essential for validating post-transcriptional regulatory effects in their native cellular environment.
  • Findings challenge previous assumptions about 3'UTR-mediated regulation of TP53.
Keywords:
3′UTR knock-outCRISPR-mediated gene editingPost-transcriptional gene regulationcancer biologydeletion of endogenous 3′UTRsgeneticsgenomicshumanmousemouse modelreporter assay

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