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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

Modulation of microRNA processing by p53

Hiroshi I Suzuki1, Kaoru Yamagata, Koichi Sugimoto

  • 1Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Nature
|July 24, 2009
PubMed

Insights

The tumor suppressor p53 enhances microRNA (miRNA) maturation after DNA damage by interacting with the Drosha complex. This reveals a new role for p53 in regulating miRNA biogenesis and tumor suppression.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • RNA Biology

Background:

  • MicroRNAs (miRNAs) are crucial post-transcriptional gene regulators with roles in both promoting and suppressing tumors.
  • Downregulation of miRNAs is common in human cancers, highlighting their tumor-suppressive significance.
  • The interplay between tumor suppressor networks and miRNA biogenesis machinery is not fully understood.

Purpose of the Study:

  • To investigate the connection between the tumor suppressor p53 and miRNA biogenesis.
  • To determine if p53 influences the processing of specific tumor-suppressive miRNAs.
  • To elucidate the mechanism by which p53 affects miRNA maturation.

Main Methods:

  • Studied the effect of p53 on miRNA processing in HCT116 cells and human diploid fibroblasts.
  • Investigated the interaction between p53, the Drosha complex, and DEAD-box RNA helicase p68 (DDX5).
  • Utilized transcriptionally inactive p53 mutants to assess the impact on miRNA processing.

Main Results:

  • p53 enhances the post-transcriptional maturation of growth-suppressive miRNAs (e.g., miR-16-1, miR-143, miR-145) in response to DNA damage.
  • p53 associates with the Drosha processing complex via p68 (DDX5), facilitating primary miRNA to precursor miRNA processing.
  • Inactive p53 mutants disrupt the p53-p68-Drosha complex assembly, impairing miRNA processing.

Conclusions:

  • p53 plays a transcription-independent role in modulating miRNA biogenesis, integral to its tumor suppressive function.
  • This newly identified function of p53 in miRNA processing offers insights into cancer biology.
  • p53's regulation of miRNA maturation represents a critical link between cellular stress response and tumor suppression.

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