Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

6.2K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
6.2K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

6.0K
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,...
6.0K
Alternative RNA Splicing02:18

Alternative RNA Splicing

22.0K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
22.0K
Translesion DNA Polymerases02:10

Translesion DNA Polymerases

10.3K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.3K
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

10.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
10.9K
RNA Splicing01:32

RNA Splicing

57.8K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
57.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies Initially Diagnosed as Immune Thrombocytopenia and Reclassified After 10 Years: Diagnostic Pitfall Revealed by a Family History.

Internal medicine (Tokyo, Japan)·2026
Same author

Drug-induced hypersensitivity syndrome followed by exacerbation of Crohn's disease.

Pediatric investigation·2026
Same author

Development and validation of the Japanese version of Sociocultural Attitudes Towards Appearance Questionnaire-4-Revised (SATAQ-4R) among Japanese adolescents.

Eating and weight disorders : EWD·2026
Same author

Delayed diagnosis of congenital duodenal obstruction in early adolescence in a patient with Down syndrome and autism spectrum disorder.

BMJ case reports·2026
Same author

Inferior Vena Cava Thrombosis Secondary to Pyomyositis and Vertebral Osteomyelitis in a 15-Year-Old Boy.

Pediatrics international : official journal of the Japan Pediatric Society·2026
Same author

Position-Dependent Detection of Hip Effusion With Point-of-Care Ultrasound in Neonatal Septic Arthritis.

Pediatrics international : official journal of the Japan Pediatric Society·2026

Related Experiment Video

Updated: Oct 17, 2025

Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells
06:48

Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells

Published on: January 5, 2024

4.4K

ALS-linked FUS mutations dysregulate G-quadruplex-dependent liquid-liquid phase separation and liquid-to-solid

Akira Ishiguro1, Jun Lu2, Daisaku Ozawa3

  • 1Research Center for Micro-Nano Technology, Hosei University, Koganei, Tokyo, Japan.

The Journal of Biological Chemistry
|October 8, 2021
PubMed
Summary

Amyotrophic lateral sclerosis (ALS) research reveals that mutations in the FUS protein disrupt its interaction with G4-RNA, leading to harmful protein aggregation. This discovery highlights G4-RNA

Keywords:
ALS (amyotrophic lateral sclerosis)FUS (fused in sarcoma)G-quadruplexLLPS (liquid–liquid phase separation)LST (liquid-to-solid transition)

More Related Videos

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
07:14

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

6.2K
Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
05:37

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

Published on: April 4, 2025

904

Related Experiment Videos

Last Updated: Oct 17, 2025

Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells
06:48

Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells

Published on: January 5, 2024

4.4K
Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
07:14

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

6.2K
Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
05:37

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

Published on: April 4, 2025

904

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease linked to protein aggregate accumulation in motor neurons.
  • Genetic mutations in ALS patients underscore the need to understand underlying molecular mechanisms.
  • Fused in sarcoma (FUS) protein, implicated in ALS, binds to G-quadruplex (G4)-DNA/RNAs.

Purpose of the Study:

  • To investigate the impact of ALS-linked FUS mutations on G4-RNA binding activity.
  • To analyze the effects of these mutations on FUS protein's phase separation and aggregation behavior.
  • To elucidate the role of G4-RNA in FUS-mediated liquid-liquid phase separation (LLPS) and liquid-to-solid transition (LST).

Main Methods:

  • Purification of full-length FUS protein and eight ALS-linked FUS mutants.
  • Analysis of FUS protein's interaction with G4-RNA.
  • Observation and characterization of FUS liquid-liquid phase separation (LLPS) and liquid-to-solid transition (LST) using purified proteins.

Main Results:

  • FUS protein undergoes liquid-liquid phase separation (LLPS) and subsequent liquid-to-solid transition (LST) forming aggregates, a process promoted by G4-RNA interaction.
  • All tested ALS-linked FUS mutants defective in G4-RNA recognition lost the regulation of G4-RNA-dependent LLPS and LST.
  • The P525L mutation, associated with juvenile ALS, showed the most significant impact on G4-RNA binding and FUS aggregation.

Conclusions:

  • G4-RNA binding is essential for regulating FUS phase separation and aggregation, crucial processes in ALS pathogenesis.
  • ALS-linked FUS mutations impair G4-RNA binding, leading to aberrant LLPS and LST, thus contributing to motor neuron degeneration.
  • These findings offer insights into the connection between protein aggregation, RNA-binding protein dysfunction, and ALS development.