Related Experiment Video

Updated: Dec 6, 2025

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
09:33

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules

Published on: May 12, 2017

14.9K

Pharmacological inhibition of DEAD-Box RNA Helicase 3 attenuates stress granule assembly

B Celia Cui1, Vitali Sikirzhytski1, Marina Aksenova1

  • 1Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA.

Biochemical Pharmacology
|October 13, 2020
PubMed

Insights

The enzymatic activity of DEAD-Box RNA helicase 3 (DDX3) is crucial for stress granule assembly. Inhibiting DDX3 reduces stress granule formation, suggesting therapeutic potential for related diseases.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Stress granules (SGs) are cytoplasmic aggregates involved in mRNA processing during cellular stress and disease.
  • DEAD-Box RNA helicase 3 (DDX3) is a key player in RNA metabolism and a therapeutic target for various diseases.
  • The precise role of DDX3's enzymatic activity in SG dynamics remains unclear.

Purpose of the Study:

  • To investigate the impact of DDX3 enzymatic activity inhibition on stress granule assembly and disassembly.
  • To evaluate the effects of two distinct DDX3 inhibitors, RK33 and 16D, on SG dynamics.

Main Methods:

  • Utilized two small molecule inhibitors (RK33 and 16D) targeting DDX3's ATPase activity and RNA helicase site.
  • Assessed the impact of DDX3 inhibition and RNA-mediated knockdown on SG assembly and disassembly.
  • Compared the effects of pharmacological inhibition versus genetic depletion of DDX3.

Main Results:

  • Both RK33 and 16D significantly reduced stress granule assembly, with RK33 showing a more pronounced effect.
  • DDX3 inhibition had a minimal impact on stress granule disassembly.
  • RNA-mediated knockdown of DDX3 mirrored the reduction in SG assembly observed with inhibitors.

Conclusions:

  • DDX3 enzymatic activity is essential for the proper assembly of stress granules.
  • Pharmacological inhibition of DDX3 presents a potential therapeutic strategy for diseases associated with stress granule dysfunction.
Keywords:
DDX3DDX3XDEAD-Box RNA helicaseRK-33Stress granule

More Related Videos

Visualization of G3BP Stress Granules Dynamics in Live Primary Cells10:12

Visualization of G3BP Stress Granules Dynamics in Live Primary Cells

Published on: May 21, 2014

18.7K
Analysis of Translation Initiation During Stress Conditions by Polysome Profiling10:59

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling

Published on: May 19, 2014

18.7K

Related Concept Videos

Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
227
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.1K
Stringent Response in E. coli01:23

Stringent Response in E. coli

Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
188
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.8K
DNA Damage can Stall the Cell Cycle02:37

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...
9.8K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.4K