A Fresh Look at Huntingtin mRNA Processing in Huntington's Disease
UMass Chan AffiliationsRNA Therapeutics Institute
Department of Medicine
Document TypeJournal Article
RNA 3’ End Processing
Biochemistry, Biophysics, and Structural Biology
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Genetics and Genomics
Nervous System Diseases
Neuroscience and Neurobiology
MetadataShow full item record
AbstractHuntington'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.
J Huntingtons Dis. 2018;7(2):101-108. doi: 10.3233/JHD-180292. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/48827
Rights© 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).
Except where otherwise noted, this item's license is described as © 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).