UMMS Affiliation
Department of Medicine; RNA Therapeutics Institute
Publication Date
2017-09-26
Document Type
Article
Disciplines
Genetic Phenomena | Molecular and Cellular Neuroscience | Nervous System Diseases
Abstract
The huntingtin gene has two mRNA isoforms that differ in their 3' UTR length. The relationship of these isoforms with Huntington's disease is not established. We provide evidence that the abundance of huntingtin 3' UTR isoforms differs between patient and control neural stem cells, fibroblasts, motor cortex, and cerebellum. Huntingtin 3' UTR isoforms, including a mid-3' UTR isoform, have different localizations, half-lives, polyA tail lengths, microRNA sites, and RNA-binding protein sites. Isoform shifts in Huntington's disease motor cortex are not limited to huntingtin; 11% of alternatively polyadenylated genes change the abundance of their 3' UTR isoforms. Altered expression of RNA-binding proteins may be associated with aberrant isoform abundance; knockdown of the RNA-binding protein CNOT6 in control fibroblasts leads to huntingtin isoform differences similar to those in disease fibroblasts. These findings demonstrate that mRNA 3' UTR isoform changes are a feature of molecular pathology in the Huntington's disease brain.
Keywords
Huntington’s disease, 3′ UTR isoforms, alternative polyadenylation, huntingtin, polyA site sequencing
Rights and Permissions
Copyright 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
10.1016/j.celrep.2017.09.009
Source
Cell Rep. 2017 Sep 26;20(13):3057-3070. doi: 10.1016/j.celrep.2017.09.009. Link to article on publisher's site
Journal/Book/Conference Title
Cell reports
Related Resources
PubMed ID
28954224
Repository Citation
Romo LS, Ashar-Patel A, Pfister EL, Aronin N. (2017). Alterations in mRNA 3' UTR Isoform Abundance Accompany Gene Expression Changes in Human Huntington's Disease Brains. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.celrep.2017.09.009. Retrieved from https://escholarship.umassmed.edu/oapubs/3252
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Genetic Phenomena Commons, Molecular and Cellular Neuroscience Commons, Nervous System Diseases Commons