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Related Experiment Video

Updated: Jun 21, 2025

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

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

Published on: December 10, 2021

CircHTT(2,3,4,5,6) - co-evolving with the HTT CAG-repeat tract - modulates Huntington's disease phenotypes.

Jasmin Morandell¹, Alan Monziani¹, Martina Lazioli¹

¹NeuroEpigenetics Laboratory, Department of Cellular, Computational, and Integrative Biology - CIBIO, University of Trento, 38123 Trento, Italy.

Molecular Therapy. Nucleic Acids

|July 8, 2024

Summary

Researchers discovered a novel circular RNA, circHTT, in the brain that is linked to Huntington's disease (HD) pathology. This circRNA may play a role in regulating protein translation and offers a new avenue for understanding HD.

Keywords:

CAG-repeat expansion Huntington's disease MT: Non-coding RNAs Neurodegeneration back-splicing circRNA

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Last Updated: Jun 21, 2025

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Published on: December 10, 2021

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Published on: February 27, 2018

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

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Published on: June 27, 2018

Area of Science:

Neuroscience
Molecular Biology
Genetics

Background:

Circular RNAs (circRNAs) are crucial for brain development and neurological disorders.
The Huntington's disease (HD) gene locus is implicated in neurodegenerative conditions.

Purpose of the Study:

To identify and characterize circRNAs associated with the Huntington's disease gene.
To investigate the function and potential role of circHTT in HD pathology.

Main Methods:

Identification and validation of circHTT(2,3,4,5,6) in human and mouse models.
Analysis of circHTT expression during development and in HD models.
Investigation of circHTT translation and ribosomal association.
Functional studies using cell-based assays (STHdh cells).

Main Results:

circHTT(2,3,4,5,6) is conserved, abundant in the CNS, and its levels correlate with CAG repeat length in HD.
Mouse circHtt(2,3,4,5,6) is developmentally regulated and upregulated with expanded CAG tracts.
circHtt(2,3,4,5,6) associates with the 40S ribosomal subunit, suggesting a role in translation regulation.
Overexpression of circHtt(2,3,4,5,6) ameliorates cell-to-substrate adhesion defects in HD models.

Conclusions:

circHTT(2,3,4,5,6) is a novel, evolutionarily conserved circRNA in the CNS linked to HD.
This circRNA may influence HD pathology through modulation of protein translation and cellular adhesion.
circHTT represents a potential therapeutic target or biomarker for Huntington's disease.