Related Experiment Video

Updated: May 28, 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

Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity

Nicolas Léveillé1, Ran Elkon, Veronica Davalos

  • 1Division of Gene Regulation, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Nature Communications
|October 27, 2011
PubMed

Insights

RNA-binding protein RBM38 regulates microRNA (miRNA) activity, crucial for p53 tumor suppressor function. Reduced RBM38 in breast cancer links to wild-type p53, revealing a new gene regulation layer.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression, interacting with messenger RNA 3'-untranslated regions.
  • RNA-binding proteins (RBPs) influence miRNA biogenesis, stability, and activity, impacting gene regulation.
  • The tumor suppressor protein p53 regulates numerous cellular processes, including development and cancer.

Purpose of the Study:

  • To identify RBPs that control miRNA access to target mRNAs.
  • To elucidate the role of RBM38 in p53-mediated gene regulation and its impact on miRNA activity.
  • To investigate the clinical relevance of RBM38 expression in human breast cancer.

Main Methods:

  • Genetic screening to identify RBPs affecting miRNA-mRNA interactions.
  • Assays to determine RBM38's effect on miRNA-mediated repression.
  • Analysis of RBM38-miRNA target sequence interactions.
  • Correlation analysis of RBM38 expression, promoter hypermethylation, and p53 status in human breast cancer cohorts.

Main Results:

  • RBM38 was identified as an RBP that modulates miRNA-mediated repression.
  • RBM38's activity is induced by p53 and is essential for p53 function.
  • RBM38 selectively interacts with uridine-rich regions near miRNA target sites, influencing target accessibility.
  • Reduced RBM38 expression due to promoter hypermethylation correlates with wild-type p53 in breast cancer patients.

Conclusions:

  • RBM38 represents a novel regulatory mechanism in p53-mediated gene expression.
  • RBM38's modulation of miRNA activity is critical for the tumor suppressive functions of p53.
  • Dysregulation of RBM38 in breast cancer may contribute to tumorigenesis, particularly in tumors with wild-type p53.

More Related Videos

Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

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 daughter...
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.
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 ends...
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...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...