Related Experiment Video

Updated: Mar 24, 2026

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

10.1K

Mutant p53 inhibits miRNA biogenesis by interfering with the microprocessor complex

F Garibaldi1, E Falcone1, D Trisciuoglio1

  • 1Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy.

Oncogene
|March 22, 2016
PubMed

Insights

Mutant p53 (mutp53) oncoproteins disrupt microRNA (miRNA) biogenesis in cancer by sequestering RNA helicases. This leads to decreased mature miRNA levels and promotes tumor suppressor roles for these miRNAs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) are often downregulated in cancers, suggesting tumor suppressor functions.
  • The mechanisms regulating miRNAs in cancer and their link to oncogenes are not fully understood.
  • Mutations in the TP53 gene create mutant p53 (mutp53) oncoproteins with gain-of-function activities.

Purpose of the Study:

  • To investigate how mutant p53 (mutp53) oncoproteins affect microRNA (miRNA) biogenesis in cancer.
  • To elucidate the molecular mechanisms underlying miRNA deregulation by mutp53.
  • To determine the functional significance of mutp53-modulated miRNAs in tumorigenesis.

Main Methods:

  • Confocal microscopy, co-immunoprecipitation, and RNA-chromatin immunoprecipitation were used to study protein-RNA interactions.
  • Assays were performed to assess the impact of p72 overexpression on mature miRNA levels.
  • Functional experiments were conducted to evaluate the tumor-suppressive roles of specific miRNAs.

Main Results:

  • Mutant p53 (mutp53) oncoproteins inhibit the post-transcriptional maturation of a subset of microRNAs (miRNAs) in cancer cells.
  • Endogenous mutp53 binds and sequesters RNA helicases p72/82 from the microprocessor complex, disrupting Drosha-pri-miRNA association.
  • Overexpression of p72 increased mature miRNA levels, and several mutp53-downregulated miRNAs exhibited tumor-suppressive functions.

Conclusions:

  • Mutant p53 (mutp53) interferes with Drosha-p72/82 association, representing a novel mechanism for miRNA deregulation in cancer.
  • This interference contributes to the reduced levels of tumor-suppressive miRNAs observed in various human cancers.
  • Targeting this mutp53-mediated pathway could offer new therapeutic strategies for cancer treatment.

More Related Videos

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells06:48

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells

Published on: June 16, 2022

2.5K
Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

316

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
4.2K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.6K
MicroRNAs01:22

MicroRNAs

12.0K
piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
7.8K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.8K