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Related Experiment Video

Updated: Jun 1, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

A natural antisense transcript at the Huntington's disease repeat locus regulates HTT expression.

Daniel W Chung¹, Dobrila D Rudnicki, Lan Yu

¹Department of Psychiatry, Division of Neurobiology, Laboratory of Genetic Neurobiology, Johns Hopkins University School of Medicine, CMSC 8-121, 600 N. Wolfe St., Baltimore, MD 21287, USA

Human Molecular Genetics

|June 16, 2011

Summary

Researchers discovered huntingtin antisense (HTTAS), a novel transcript regulating the huntingtin gene (HTT) implicated in Huntington's disease (HD). HTTAS expression levels, particularly HTTAS_v1, are reduced in HD patients and impact HTT levels, suggesting a new therapeutic target for HD.

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

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Last Updated: Jun 1, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

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Published on: February 27, 2018

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

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Published on: December 10, 2021

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

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

Published on: June 27, 2018

Area of Science:

Neurogenetics
Molecular Biology
Gene Regulation

Background:

Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat expansion in the huntingtin (HTT) gene.
The genomic features and functional relevance of the antisense strand at the HD locus remain largely unexplored.
Previous studies suggested the existence of antisense transcripts through transcriptome surveys and EST tags.

Purpose of the Study:

To identify and characterize natural antisense transcripts at the Huntington's disease repeat locus.
To investigate the regulatory role of these antisense transcripts on huntingtin (HTT) gene expression.
To explore the potential impact of repeat length on antisense transcript function and HTT regulation.

Main Methods:

Identification and characterization of the huntingtin antisense transcript (HTTAS), including its splicing variants (HTTAS_v1, HTTAS_v2).
Reporter assays to assess promoter activity and the effect of repeat length on efficiency.
Expression analysis in human HD frontal cortex and cell systems using overexpression and siRNA knockdown.
Minigene constructs to confirm regulatory effects and dependence on repeat length and Dicer.

Main Results:

HTTAS, a natural antisense transcript containing the repeat tract, was identified and characterized with two alternatively spliced variants.
HTTAS_v1 exhibits reduced promoter efficiency with repeat expansion and is downregulated in human HD frontal cortex.
Overexpression of HTTAS_v1 decreases endogenous HTT transcript levels, while its knockdown increases HTT levels, demonstrating a regulatory role.
The regulatory effect of HTTAS_v1 on HTT is dependent on repeat length and Dicer.

Conclusions:

Strong evidence supports the existence of a functional gene antisense to HTT (HTTAS).
HTTAS, particularly HTTAS_v1, plays a significant role in regulating HTT expression.
The findings suggest that HTTAS-mediated regulation of HTT is influenced by CAG repeat length, offering potential insights into HD pathogenesis.