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

Published on: August 4, 2019

Repression of RNA polymerase I transcription by the tumor suppressor p53

W Zhai1, L Comai

  • 1Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

Molecular and Cellular Biology
|July 27, 2000
PubMed

Insights

The tumor suppressor protein p53 inhibits RNA Polymerase I (Pol I) transcription by blocking the assembly of essential transcription factors on rRNA genes. This mechanism explains how p53, a key regulator, impacts cellular processes and cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • The tumor suppressor protein p53 is crucial in preventing cancer and is frequently inactivated in tumors.
  • p53 acts as a transcriptional regulator for RNA Polymerase II (Pol II) and RNA Polymerase III (Pol III).
  • Evidence suggests p53 also suppresses RNA Polymerase I (Pol I) transcription, a process vital for ribosome biogenesis.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which p53 inhibits RNA Pol I transcription.
  • To investigate the interaction of p53 with components of the Pol I transcription machinery.

Main Methods:

  • Cotransfection assays using human rRNA gene promoters.
  • Cell-free transcription systems with recombinant p53.
  • Protein-protein interaction assays and template commitment assays.
  • Comparison of Pol I transcriptional activity in p53-null versus p53-expressing cells.

Main Results:

  • Wild-type p53, but not mutant p53, represses human rRNA gene promoter activity.
  • Recombinant p53 inhibits rRNA transcription in vitro.
  • p53-null cells show higher Pol I activity than p53-expressing cells, despite similar Pol I factor levels.
  • p53 directly binds to SL1 (specifically TBP and TAF(I)110) and inhibits the formation of the UBF-SL1-Pol I pre-initiation complex on the rDNA promoter.

Conclusions:

  • p53 represses RNA Pol I transcription by directly interfering with the assembly of the transcriptional machinery on the rRNA promoter.
  • The interaction between p53 and SL1 is a key step in inhibiting Pol I transcription.
  • Understanding this mechanism provides insights into p53's role as a tumor suppressor and its regulation of ribosome biogenesis.

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