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

Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

166
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show...
166
Alternative RNA Splicing02:18

Alternative RNA Splicing

20.5K
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...
20.5K
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

42
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and...
42
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

7.1K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.1K
Exon Recombination02:32

Exon Recombination

3.1K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon...
3.1K
RNA Splicing01:32

RNA Splicing

53.5K
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...
53.5K

You might also read

Related Articles

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

Sort by
Same author

CD4<sup>+</sup> T cells reactive to Epstein-Barr virus late lytic antigens are enriched in individuals with multiple sclerosis.

Science translational medicine·2026
Same author

Endothelial TGFβ signaling modulates choroidal neovascularization severity via myeloid-endothelial cell interaction.

Frontiers in immunology·2026
Same author

Nuclear RNA clusters are dynamic structural entities in Huntington's disease.

Communications biology·2026
Same author

Deletion of CEACAM1 does not affect retinal and choroidal morphology or transcriptome.

Cell and tissue research·2026
Same author

VEGFR2 deletion increases susceptibility to photoreceptor degeneration through glial-neuronal interaction.

Cell death & disease·2026
Same author

Germline Whole-Genome Sequencing in Early-Onset Pediatric Solid Tumors Implicates Novel Risk Factors.

JCO precision oncology·2026

Related Experiment Video

Updated: May 5, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

9.0K

Aberrantly spliced HTT, a new player in Huntington's disease pathogenesis.

Theresa A Gipson1, Andreas Neueder2, Nancy S Wexler3

  • 1Koch Institute for Integrative Cancer Research; Massachusetts Institute of Technology; Cambridge, MA USA.

RNA Biology
|November 22, 2013
PubMed
Summary

Huntington's disease (HD) pathogenesis may involve mis-splicing of the huntingtin gene (HTT), producing a pathogenic exon 1 protein fragment. This novel mechanism offers new therapeutic targets for HD.

Keywords:
HTT exon 1Huntington’s diseaseSRSF6huntingtin fragmentmis-splicing

More Related Videos

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
11:22

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Published on: June 27, 2018

12.0K
Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
10:52

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

Published on: December 10, 2021

4.6K

Related Experiment Videos

Last Updated: May 5, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

9.0K
Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
11:22

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Published on: June 27, 2018

12.0K
Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
10:52

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

Published on: December 10, 2021

4.6K

Area of Science:

  • Neurodegenerative diseases
  • Molecular genetics
  • RNA splicing

Background:

  • Huntington's disease (HD) is a fatal neurodegenerative disorder linked to expanded CAG repeats in the huntingtin gene (HTT).
  • Mutant HTT protein fragments are implicated in HD pathogenesis, but the origin of small N-terminal fragments remained unclear.
  • Previous research identified cleavage sites, suggesting proteolysis as the source of fragments.

Purpose of the Study:

  • To investigate the hypothesis that mis-splicing, not proteolysis, generates the smallest N-terminal huntingtin fragment in HD.
  • To elucidate a novel molecular mechanism contributing to Huntington's disease pathogenesis.

Main Methods:

  • Analysis of huntingtin fragments in a mouse model.
  • Demonstration of HTT intron 1 mis-splicing.
  • Identification of a short, polyadenylated mRNA transcript.
  • Translation of the transcript into an exon 1 protein.

Main Results:

  • Mis-splicing of mutant huntingtin intron 1 was confirmed.
  • This mis-splicing produces a pathogenic exon 1 protein fragment.
  • Transgenic mice with human huntingtin exon 1 exhibit rapid HD-like symptoms.
  • A novel mechanism involving mis-spliced HTT transcripts and exon 1 protein production in HD was identified.

Conclusions:

  • Mis-splicing of HTT intron 1 is a key mechanism generating pathogenic exon 1 protein in Huntington's disease.
  • This finding provides new insights into HD molecular pathogenesis.
  • The identified mechanism has significant implications for developing novel therapeutic strategies for HD.