RNA Therapeutics Institute Publications

UMMS Affiliation

Department of Medicine; RNA Therapeutics Institute

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetics and Genomics | Nervous System Diseases | Neuroscience and Neurobiology | Therapeutics


Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a mutation that expands the polyglutamine (CAG) repeat in exon 1 of the huntingtin (HTT) gene. Wild-type HTT protein interacts with other proteins to protect cells against toxic stimuli, mediate vesicle transport and endocytosis, and modulate synaptic activity. Mutant HTT protein disrupts autophagy, vesicle transport, neurotransmitter signaling, and mitochondrial function. Although many of the activities of wild-type HTT protein and the toxicities of mutant HTT protein are characterized, less is known about the activities of HTT mRNA. Most putative HD therapies aim to target mutant HTT mRNA before it is translated into the protein. Therefore, it is imperative to learn as much as we can about how cells handle both wild-type and mutant HTT mRNA so that effective therapies can be designed. Here, we review the structure of wild-type and mutant HTT mRNA, with emphasis on their alternatively polyadenylated or spliced isoforms. We then consider the abundance of HTT mRNA isoforms in HD and discuss the potential implications of these findings. Evidence in the review should be used to guide future research aimed at developing mRNA-lowering therapies for HD.


Huntington disease, mRNA, 3’UTR, alternative splicing, RNA 3’ End Processing

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© 2018 – IOS Press and the authors. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0).

DOI of Published Version



J Huntingtons Dis. 2018;7(2):101-108. doi: 10.3233/JHD-180292. Link to article on publisher's site

Journal/Book/Conference Title

Journal of Huntington's disease

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License